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I. POIma anU bnOIma NOOU j
Abnormal Mood
Mania Q
Hypo mania 1j
Thc Syndromc of Ocprcssion 1)
Mbcd Statcs 2j
2. JC a_nO88 O! DQOaI 8OIUCI 2o
Psychiatric Oiagnosis 2Q
5ipolar I j
5ipolar II j)
Cyclothymic Oisordcr q1
5ipolar Spcctrum Oisordcrs qq
Rapid- Cycling 5ipolar Oisordcr qQ
Schizoahcctivc Oisordcr j
DQOaI 8OIUCI anU !hC L- jq
What Is thc L! jq
5ipolar Catcgorics in thc Lj j)
JC NOOU 8Ca8C jo
5cfrc "5ipolar jo
Or. Kracpclin and "Manic- Ocprcssivc Insanity
Or. Cadc and Lithium j
JC a8!C DIan )1
. NOOU-5!abZn_ NCUCa!On8 ))
Lithium ))
Lamotriginc [Lamictal) o
Valproatc [Ocpakotc, Ocpakcnc, Lpival) oQ
Carbamazcpinc [Tcgrctol, Lguctro, Lpitol) Q2
xcarbazcpinc [Trilcptal) Qq
thcr Mood Stabilizcrs Qj
n thc Horizon. Promising cw Approachcs Q
n!UCQIC88an! NCUCa!On8 Qo
Tricyclic Antidcprcssants Qo
Sclcctivc Scrotonin Rcuptakc Inhibitors 1
cw Antidcprcssants 11
Monoaminc xidasc Inhibitors 12
Trcating 5ipolar Ocprcssion 1q
b. n!Q8yChO!C NCUCa!On8 1)
Typical Antipsychotic Mcdications 1o
Atypical Antipsychotic Mcdications 11

NOIC NCUCa!On8, OImOnC8, anU C!aIy 5uQQCmCn!8 11j
Mcdications fr Anxicty and Slccp Oisturbanccs 11j
Thyroid Hormoncs 11)
Hcrbal Prcparations and utritional Supplcmcnts 11Q
mcga- Iatty Acids and Iish il 12
- Acctyl Cystcinc 12
St. [ohn`s Wort 121
IO. DIan-5!mua!On JICa!mCn!8 12q
Llcctroconvulsivc Thcrapy 12q
Transcranial Magnctic Stimulation 1j
Vagal crvc Stimulation 1j2
Lmcrging Tcchnologics 1j2
11. LOun8Cn_ anU 8yChO!hCIaQy 1jq
5rain and Mind 1jj
What Can Thcrapy Oo 1j)
Croup Psychothcrapy 1jo
Individual Thcrapy fr Ocprcssion 1jQ
cw Psychothcrapics fr 5ipolar Oisordcr 1q2
"Traditional Individual Psychothcrapy 1qq
Psychothcrapy in 5ipolar Oisordcr. Is It Rcally cccssary 1q
Thc Psychiatrist- Psychothcrapist. An Lxtinct Spccics 1q)
1l. JICa!mCn! QQIOaChC8 n DQOaI 8OIUCI 1qo
Thcrapcutic Rcsults as a Cuidc to Trcatmcnt 1qo
Somc Principlcs of Trcatmcnt 1j1
1. DQOaI 8OIUCI n LhUICn anU UOC8CCn!8 11
Symptoms of Pcdiatric 5ipolar Oisordcr 1j
5ipolar Oisordcr and Attcntion-Ochcit Hypcractivity Oisordcr 1q
Trcatmcnt and Prognosis 1j
1q. YOmCn wm DQOaI 8OIUCI: 5QCCa LOn8UCIa!On8 1Q
Symptom Oihcrcnccs in Womcn 1Q
Postpartum Mood Oisordcrs and Iamily Planning 1)
Prcmcnstrual Syndromcs 1)2
1]. COhO8m anU Iu_ bu8C 1)q
5ipolar 5ingcs 1)q
Lhcct, Causc, or Association 1)o
Lsc or Abusc 1)o
A Ocadly Combination 1)Q
Trcating Substancc Abusc and Addiction 1o
1. JC 5CCnCC O! LyCC8: LhIOnObOO_y 1oq
Circadian Rhythms 1o
Scasonal Ahcctivc Oisordcr 1oo
Thc Slccp Cyclc and 5ipolar Oisordcr 1oQ
1). JC LCnC!C8 O! DQOaI 8OIUCI 1Qj
Ccncs, Chromosomcs, and OA 1Qj
Ccnctic Oiscascs 1Qj
What Wc Know 1Qj
Thc Scarch Continucs 1Q
1. DQOaI DOO_y
How thc 5ody Handlcs Strcss
5ipolar Oisordcr and Hormonal Systcms
Picturing 5ipolar Oisordcr in thc 5rain
1. DQOaI 8OIUCI anU LICa!v!y
lO. Lvn_ W!h DQOaI 8OIUCI
Conhont and Acccpt thc Illncss
Practicc Mood Hygicnc
5uild Your Support Systcm
Oon`t 5c a "5ipolar Victim`'
l1. annn_ I mCI_CnCC8
Know Whom to Call fr Hclp
Insurancc Issucs
Safcty Issucs and Hospitalization
ll. JC OC O! !hC amy
Rccognizing Symptoms
Involuntary Trcatmcnt and thcr Lcgal Issucs
Morc on Safcty
Cctting Support
l. LOOKn_ hCaU
Suggested Reading
Support and Advocacy Organizations
Internet Resources
About 2 pcrccnt of thc population suhcrs hom somc frm of bipolar dis-
ordcr. Winston Churchill, Ccorgc Iridcric Handcl, Lord 5yron, Virginia
Woolf, Ldgar Allan Poc, apolcon 5onapartc, and Vinccnt van Cogh arc
only a fcw of thc politicians, writcrs, artists, and musicians who, dcspitc
having bipolar disordcr, lch a mark of grcatncss upon thc world. ' Most pcr-
sons who arc ahcctcd by this illncss, howcvcr, arc ordinary pcoplc who want
nothing morc than to gct back to thcir cvcryday livcs ahcr thcy or thcir
fmily mcmbcrs havc bccn diagnoscd with it. This book is writtcn fr thcm.
Wc psychiatrists havc at timcs bccomc a littlc complaccnt about this dis-
casc. Whcn lithium bccamc widcly availablc in thc Lnitcd Statcs in thc mid-
I;os, many psychiatrists thought thc battlc to control thc illncss had bccn
won. Indccd, lithium was-and still is-a miraclc drug fr many pcoplc who
suhcr hom what was thcn known as manic- dcprcssion. Morc rcccnt studics
indicatc that a substantial proportion of paticnts-according to somc stud-
ics, as many as half-havc a rclapsc of thcir illncss dcspitc taking lithium. '
5ut cvcn as wc bccomc morc awarc of thc sobcring fcts about thc dimculty
of succcssmlly trcating bipolar disordcr, an cxplosion of dcvclopmcnts in
scicncc and mcdicinc holds grcat promisc fr thosc ahcctcd by thc discasc.
In this book I shall rclatc this good ncws.
Clinical rcscarch has shown again and again that many rclapscs of bi-
polar disordcr occur not bccausc of mcdication filurc, but rathcr bccausc
paticnts stop taking mcdication and drop out of trcatmcnt. Pcrhaps paticnts
don`t undcrstand that rclapsc and rcpctition of illncss cpisodcs arc thc hall-
mark of thc illncss, that a|ru||y stopping mcdication has bccn shown to
bc cspccially ris|, that mcdication sidc chccts can ohcn bc trcatcd or con-
trollcd, and that ncw mcdications arc bccoming availablc all thc timc. I hopc
this book hclps thosc who fcc dimcult trcatmcnt dccisions to makc wcll-
infrmcd and intclligcnt choiccs.
A survcy of paticnts with bipolar disordcr and othcr mood disordcrs,
carricd out by thc ational Ocprcssivc and Manic-Ocprcssivc Association
[now, thc Ocprcssion and 5ipolar Support Alliancc) in thc carly Ios, fund
that 6 pcrccnt of thosc who rcspondcd to thc gucstionnairc had not sought
profcssional trcatmcnt until morc than |cnycars ahcr thcir symptoms had
bcgun. `f thc bipolar paticnts in this study, ; pcrccnt had rcccivcd at lcast
onc incorrcct diagnosis bcfrc bcing idcntihcd as having bipolar disordcr-
ohcn many ycars ahcr hrst sccking hclp. Thc avcragc rcspondcnt had sccn
. physicians bcfrc bcing corrcctly diagnoscd. Why is this illncss so dim-
cult to idcntify corrcctly nc rcason is that mll-blown manic- dcprcssivc ill-
ncss is only onc of thc scvcral frms this chamclcon disordcr can takc-and
manic- dcprcssivc illncss may in fct bc lcss common than thc mildcr frms
[thc so- callcd soh bipolar disordcrs) , in which symptoms of mild dcprcs-
sion and subtlc "mood swings may bc thc only manifcstations of bipolar
disordcr. Wc arc rcalizing that many paticnts with thcsc mildcr frms of
thc disordcr bcncht hom trcatmcnt with mood-stabilizing mcdications, too.
5ut thcy can do so only i f thcy scck trcatmcnt and arc corrcctly diagnoscd.
Wc shall scc why many paticnts who havc a bipolar disordcr arc told thcy
havc "only dcprcssion`' or a "pcrsonality disordcr and shall also scc thc con-
scgucnccs of thcsc and othcr diagnostic crrors .
Likc any othcr scrious illncss, bipolar disordcr ahccts not only thc pcr-
son who suhcrs hom thc discasc but family, hicnds, and collcagucs as wcll.
Iamily support is crucial to thc chcctivc managcmcnt of symptoms. Thc dis-
ruptcd rclationships and intcrpcrsonal conflicts that thc symptoms of thc ill-
ncss can causc makc bipolar disordcr all thc morc dimcult and complicatcd
to trcat. Infrmation and undcrstanding arc dchnitcly part of thc trcatmcnt
fr this discasc, and this book was writtcn not only fr thc paticnt but fr thc
paticnt's fmily and hicnds as wcll.
5ipolar disordcr can bc a ftal discasc. Although thc hgurcs vary among
studics, about Iy pcrccnt of pcrsons with bipolar disordcr commit suicidc,'
many morc makc suicidc attcmpts. Thcsc arc prcvcntablc dcaths, bccausc
vcry chcctivc trcatmcnts fr this illncss cxist. I hopc that thc infrmation
this book providcs about thc trcatmcnt of bipolar disordcr addrcsscs somc
of thc rcasons why individuals arc rcluctant to cntcr trcatmcnt and dissuadcs
somc hom stopping trcatmcnt against mcdical advicc. Ycs, it is my hopc that
this book will savc livcs.
A H 1
^`^ ^`JJ^
.J JJ.!^J^
A profcssor of minc oncc told mc, "Whcn you can't hgurc out wba|
thc paticnt has, hc or shc probably has bipolar disordcr.' I rcmcmbcr
thinking at thc timc that this was onc of thc most folish things I had
cvcr hcard a [ohns Hopkins fculty mcmbcr say. 5ut ovcr thc ycars I
havc comc to rcalizc that hc was right.
5ipolar disordcr is thc chamclcon of psychiatric disordcrs, chang-
ing its symptoms hom onc paticnt to thc ncxt and hom onc cpisodc
of illncss to thc ncxt cvcn in thc samc paticnt. It is a phantom that can
sncak up on its victim cloakcd in thc darkncss of mclancholy but thcn
disappcar fr ycars at a timc-only to rcturn in thc rcsplcndcnt but
hcry robcs of mania. Although both dcprcssion and mania had bccn
dcscribcd ovcr two millcnnia prcviously by Crcck and Pcrsian physi-
cians-scvcral of whom thought thc conditions wcrc linkcd in somc
way-it wasn't until thc carly part of thc twcnticth ccntury that a Ccr-
man psychiatrist, Lmil Kracpclin, convincingly prcscntcd thc idca that
thcsc oppositc conditions wcrc two sidcs of onc pathological coin, thc
two prohlcs of a [anus- fccd discasc that hc callcd manic- dcprcssivc
Why did it takc morc than two thousand ycars fr somconc to
solvc a puzzlc having only two picccs 5ccausc, as my profcssor kncw,
thcrc arc so many morc than two picccs to this mystcrious disordcr.
Thc dcprcsscd phasc can bc mcrcly gloomy or profundly dcspairing,
torpid and lcthargic, or agitatcd and churning. Thc manic phasc can bc
no morc than an cnthusiastic glow, or it can bc an cxultant, transccn-
dcntal fcrvor, hcnzicd panic, or dclirious, crashing, raving psychosis.
Somctimcs oppositc moods sccm to bc combincd, as inscparablc as
smokc and hrc, mood statcs that havc bccn givcn namcs likc dcrcss|vc
man|a, man|cs|ucray||a|cddcrcss|cn,and morc rcccntly and morc
simply, m|xcds|a|cs.Thc tcndcncy of thc illncss to hibcrnatc-fr
symptoms to spontancously disappcar fr ycars, cvcn dccadcs at a
timc-adds to thc conmsion, pcrplcxing thc diagnostician and lulling
thc paticnt into dangcrous complaccncy rcgarding thc nccd fr trcat-
In this hrst part of thc book, thcrc arc fur chaptcrs cxamining thc
symptoms, thc syndromcs, and thc diagnosis of bipolar disordcr. In
chaptcr i, "ormal and Abnormal Mood,' wc rcvicw thc many symp-
toms of bipolar disordcr, collcctcd into thrcc main clustcrs. man|a, dc-
rcss|cn,and thc m|xcdmccds|a|cs.I havc not minimizcd thc scvcrity
of thc symptoms in this chaptcr, I prcscnt all thc possiblc symptoms of
thc illncss, many of thcm hightcning and tcrriblc. 5ut it is important
to rcmcmbcr, hrst, that not cvcry pcrson with bipolar disordcr dcvcl-
ops all thc possiblc symptoms, and sccond, that modcrn trcatmcnts
usually prcvcnt thc dcvclopmcnt of thc worst of thcm, many of which
arc now rarcly sccn cvcn by psychiatrists.
Thc dihcrcnt frms thc disordcr can takc is thc subjcct of chaptcr
2, " Thc Oiagnosis of 5ipolar Oisordcr.' Thc diagnosis of bipolar disor-
dcr is complcx, and thcrc is still somc disagrccmcnt about how thc dif-
fcrcnt symptom clustcrs arc rclatcd to onc anothcr. Arc thcrc scvcral
dihcrcnt discascs of mood with dihcrcnt causcs Is thcrc a group of
disordcrs that sharc common fcaturcs andcommon causcs Arc thcsc
illncss frms csscntially thc samcdisordcr dihcring only in dctails
of cxprcssion Oo thcsc dihcrcnt frms rcmain thc samc ovcr timc
in cach paticnt, or can onc frm dcvclop into anothcr Thc answcrs
to somc of thcsc gucstions rcmain unknown. cvcrthclcss, thcrc arc
scvcral frms of thc illncss that can bc rcliably idcntihcd and scparatcd
hom onc anothcr. Idcntiing onc or anothcr of thcsc frms allows
fr prcdictions about thc coursc of thc illncss ovcr timc and about thc
typc of trcatmcnt that has thc bcst chancc of bcing chcctivc.
Chaptcr j, "5ipolar Oisordcr and thc DSA-y, rcvicws thc omcial
classihcation systcm fr thc illncss that is currcntly uscd by thc Amcr-
ican Psychiatric Association [and by many psychiatrists throughout
thc world). This chaptcr might bc considcrcd optional rcading and will
probably bc of morc intcrcst to studcnts and profcssionals conccrncd
with thc dctails of illncss classihcation and diagnostic catcgorics.
In chaptcr q," Thc Mood Oiscasc,' I show how psychiatrists camc
to rcalizc that bipolar disordcr is indccd a discasc. Ior dccadcs, pcr-
sons amictcd with mood disordcrs wcrc ohcn givcn thc covcrt mcssagc
by thcir physicians that thcy thcmsclvcs wcrc to blamc fr thcir symp-
toms. Ocprcssion and othcr mood symptoms wcrc blamcd on cmo-
tional immaturity or "maladjustmcnt rathcr than bcing rccognizcd
as cxprcssions of disordcrcd mnctioning of thc brain. It was only with
thc discovcry of chcctivc pharmaccuticals that psychiatry rcalizcd that
bipolar disordcr is indccd a discasc-as rcal as diabctcs or hypcrthy-
L M A 1 H
^O1Hd1 dDU 1DDO1Hd1 NOOU
disordcrs whosc main symptom is an abnormality of mood. Thc hrst stcp
in undcrstanding thc illncss, thcn, is to undcrstand what wc mcan by thc
word mccd. Pcrhaps morc to thc point, I want to talk about what sycb|a-
|r|s|smcan by thc word. Thc dictionary isn't much hclp hcrc, it dchncs mccd
simply as "a conscious statc of mind or prcdominant fccling.'' Thc "prc-
dominant fccling'' part of this dchnition bcgins to capturc thc psychiatric
conccpt, but mood is much morc than just a fccling.
ur mood includcs our happincss or sadncss, our statc of optimism or
pcssimism, our fcclings of contcntcdncss or dissatisfction with our situ-
ation, and cvcn physical fcclings such as how ftigucd or robust wc fccl.
Mood is likc our cmotional tcmpcraturc, a sct of fcclings that cxprcsscs our
scnsc of cmotional comfrt or discomfrt.
Whcn individuals arc in a good mood, thcy arc conhdcnt and opti-
mistic, rclaxcd and hicndly, paticnt, intcrcstcd, contcnt. Thc word bay
capturcs part of it, but good mood includcs a lot morc. Pcoplc in a good
mood usually fccl cncrgctic and havc a scnsc of physical wcll-bcing, thcy
slccp soundly and cat hcartily. It's casy fr thcm to bc sociablc and ahcction-
atc. Thc mturc looks bright and thc momcnt ripc fr starting ncw proj ccts.
Whcn wc'rc in a good mood, thc world sccms a wondcrml placc to livc in, it
fccls good to bc alivc.
Whcn wc'rc in a low mood, an oppositc sct of fcclings takcs ovcr. Wc
tcnd to turn inward and may sccm prcoccupicd or distractcd by our thoughts.
Thc word sad capturcs somc of thc cxpcricncc, but low mood is a bit morc
complicatcd. Thcrc may bc a scnsc of cmptincss and loss. It's dimcult to
think about thc mturc vcry much, and whcn onc docs, it's hard not to bc
pcssimistic or cvcn intimidatcd by it. Wc may losc our tcmpcr morc casily
and thcn fccl guilty about having donc so. It's dimcult to bc ahcctionatc or
sociablc, so wc avoid othcrs and prcfcr to bc alonc. Lncrgy is low. Sclf- doubt
takcs ovcr, wc bccomc prcoccupicd, worrying about how othcr pcoplc scc us.
AhnormaI Mood
Somc of lifc's morc common strcsscs and thc normal human rcactions
to thcm arc such common cxpcricnccs that common tcrms havc bccn
coincd fr somc mood changcs-and most pcoplc rccognizc thcsc mood
changcs as guitc normal. Moving to a ncw community whcrc wc don't know
anyonc ohcn lcads to a scnsc of dislocation and lonclincss that wc know
as homcsickncss, an unplcasant cxpcricncc that may last fr days or cvcn
wccks and that cvcryonc has probably cxpcricnccd at onc timc or anothcr.
Whcn somconc closc to us dics, a profund scnsc of sadncss and loss-thc
dccp sorrow that wc call bcrcavcmcnt or mourning-occurs, and it can bc-
comc tcmporarily incapacitating. Whcn wc comc to various milcstoncs of
pcrsonal achicvcmcnt, wc cxpcricncc changcs of mood i n thc othcr dircc-
tion. A graduation or wcdding or thc birth of a child can hll a pcrson with
joy and pridc and a scnsc of limitlcss optimism that arc ncarly ovcrwhclm-
ing. Wc wouldn`t call any of thcsc moods "abnormal,' cvcn though thcy may
bc cxtrcmc.
Likc many othcr things wc can mcasurc in human bcings-body tcm-
pcraturc, blood prcssurc, and hormonc lcvcls, fr cxamplc-a pcrson`s mood
statc normally varics within a ccrtain rangc. Pcoplc arc not i n thc samc mood
statc all thc timc, i t i s guitc normal to havc ups and downs of mood. Oo pcr-
sons with bipolar disordcr simply havc highcr ups and dccpcr downs Wcll,
it's ccrtainly truc that thc bipolar paticnt's ups and downs arc somctimcs so
fr outsidc thc rangc of normal that it docsn`t takc a psychiatrist to know that
somcthing is vcry wrong. Thc abnormal mood statcs of bipolar disordcr arc
accompanicd by changcs in thinking and bodily mnctions, changcs that mr-
thcr dcmarcatc thcm hom normal mood. Lxamplcs includc slccplcssncss,
changcs in appctitc, impaircd conccntration and mcmory, and problcms
with motivation and cncrgy lcvcl. To say that pcrsons with bipolar disordcr
simply havc morc cxtrcmc ups and downs of mood isn`t cvcn ncarly right.
Thc symptoms of bipolar disordcr, which sccm to bc causcd by a dcfcct in
thc brain`s rcg|a||cnof mood, also spill ovcr to othcr arcas of mnctioning.

Laura is a frty-ycar-old vicc prcsidcnt of onc of thc largcst banks in
thc country.' Whcn I walkcd out into thc waiting room to call hcr fr
our hrst appointmcnt, shc was sitting with a laptop computcr balanccd
on hcr knccs and a ccll phonc hcld up to hcr car. "o, Stcvc, that's not
good cnough,' shc was saying into thc phonc as shc noddcd to mc.
"o, that won`t work cithcr, wc nccd thc last guartcr's rca|numbcrs,
not an cstimatc. Listcn, I'm . . . ah . . . in thc doctor's omcc. I'll call you
in an hour.' I raiscd my cycbrows and shook my hcad. "Makc that two
hours. 5yc.' Click, click, snap, phonc and computcr wcrc shut, and in a
momcnt wc wcrc sitting in an intcrvicwing room.
"I madc this appointmcnt as soon as I could ahcr I rcad this.'
Laura handcd mc a pamphlct that thc local chaptcr of thc Ocprcssion
and 5ipolar Support Alliancc had bccn handing out at a local shopping
mall during a hcalth fir rcccntly. "I'vc known fr ycars that somcthing
was wrong, but I didn`t know what. Rcading this has madc mc think
mcdication might hclp.'
"What havc you noticcd that's `wrong' I askcd.
"I go into thcsc, thcsc |b|nys,shc startcd. "I gct this wircd, can`t-
slow- down fccling. I'vc always callcd it `thc crazics, and I usually crash
ahcr it's ovcr. Somctimcs I can't gct out of bcd fr days.'
"You sccm to havc a vcry high strcss j ob,' I ohcrcd. "Maybc that's
part of thc problcm.'
"You sound likc my mothcr. `You don`t havc to takc cvcrypromo-
tion thcy ohcr you, shc says. 5ut this isn`t just strcss, thcrc's somcthing
clsc going on. Thc worst part is, I think thcsc things arc gctting worsc.'
Laura`s usc of phrascs likc "thc crazics and "thcsc things sccmcd
to indicatc that shc fclt that thcsc fcclings wcrc frcign, not likc hcr
normal fcclings.
"Arc you saying that somctimcs your fcclings and moods arc con-
trolling you rathcr than thc othcr way around I askcd.
Laura sat up straight in hcr chair. " That's thc bcst way I could pos-
sibly dcscribc it,' shc said dccisivcly. "I can }cc|thcm coming on, it's
almost physical. 5ut I know thcy'rc . . . wcll, mcn|a|,I gucss, is thc bcst
way to put it' Hcr fcc suddcnly cloudcd ovcr. "Oocs this mcan I'm
mcntally ill
"Wcll,' I said, "wc know that thcrc arc illncsscs that ahcct mood,
and mood is ccrtainly a mcntal statc. 5ut wc havc a lot morc to talk
about bcfrc I'll bc ablc to say just what cxplains what you'rc going
Laura lookcd slightly rclicvcd and said, "Wcll, that's why I'm hcrc,
iLVA1 i1iLVA1 ALL1 M ,
fr an cxplanation.' Shc pickcd thc brochurc up hom thc cdgc of
thc dcsk. " This is thc bcst cxplanation I'vc comc across yct,' shc said
thoughtmlly. "And that mcans I can gct rid of thcm, right Thcrc's a
trcatmcnt that will gct rid of thcm
"Thcrc arc many trcatmcnts fr mood disordcrs. It may just takc
somc timc to hnd thc onc that works bcst.'
"Thcn I camc to thc right placc,' shc said as shc sat back in hcr
chair again. " `You'rc not crazy, my mothcr said. `You don`t nccd to scc
a psychiatrist
"Wcll, I think your mothcr was at lcast half right,' I said.
Laura smilcd fr thc hrst timc. "K, thcn lct's- Suddcnly a
bccp-bccp-bccp soundcd hom hcr jackct pockct. Shc took out hcr ccll
phonc again. "If that's, um, conhdcntial,' I ohcrcd, "I can-
Laura pushcd a button, and thc bccping stoppcd. Shc put thc
phonc back in hcr pockct. "o, that can`t possibly bc as important as
this. It can wait. I want to givc you my undividcd attcntion.'
"Lxccllcnt| I thought to mysclf. "This is a woman who undcr-
stands prioritics.'

Imaginc a pcrson whosc tcmpcraturc rcgulation systcm docsn`t work
corrcctly-a pcrson who suddcnly starts shivcring on a warm sunny day or
brcaks out into a swcat in a room in which cvcryonc clsc is chilly. This pcr-
son`s rcactions to warm and cold arc abnormal, hcr body "thinks it is cold
whcn it isn`t and shc fccls hot whcn thc tcmpcraturc is cool. Wc can think of
mood disordcrs as problcms with cmc||cna|tcmpcraturc rcgulation.
In mood disordcrs, thc mood bccomcs disconncctcd hom thc indi-
vidual's cnvironmcnt, and "happy and "sad fcclings takc on rhythms and
fluctuations of thcir own. Somctimcs thc fluctuations arc mild, and thc af-
fcctcd pcrson only sccms to havc mcrc ups and downs than othcr pcoplc
havc and to havc mood fluctuations that arc morc dimcult to undcrstand.
5ut bccausc such individuals don't gct profundly dcprcsscd or irrationally
"high,' thcir problcms arc dismisscd as bcing duc to a dimcult pcrsonality
or to "immaturity.' Somctimcs, though, thc mood statcs arc so cxtrcmcly
abnormal that a pcrson`s ability to judgc rcality is shattcrcd, his bchavior can
bc bizarrc and hightcning. [It is in somc of thcsc cascs that a diagnosis of
schizophrcnia can bc mistakcnly madc, with thc rcsult that propcr trcatmcnt
gocs wanting. ) If thc mood- disordcr paticnt and his situation arc cxamincd
with cnough carc, howcvcr, thc basic undcrlying problcm, thc rcgulation of
mood, will bc fund.
It is bccausc thc basic problcm is rcyu|a||cn of mood that thc disordcr
can prcscnt dihcrcnt symptoms at dihcrcnt timcs. Pcrsons amictcd with thc
classic frm of thc illncss havc pcriods of scvcrc dcrcss|cnas wcll as pcriods
of man|a[a mood statc that is in somc ways thc oppositc of dcprcssion) . Thc
obscrvation that both of thcsc mood statcs occur at various timcs during
thc coursc of thc illncss gavc risc to thc oldcr namc fr thc disordcr . manic-
dcprcssivc illncss. Thcsc oppositc moods occur in ahcctcd pcrsons bccausc
thc brain mcchanisms that normally rcgulatc mood don't work propcrly.
This obscrvation-that thc mood statcs of ahcctcd pcrsons movc to cithcr
of thc two polar oppositc cxtrcmcs of mood-givcs thc disordcr its modcrn
namc, bipolar disordcr. In thc fllowing scctions wc'll takc a closcr look at
thcsc oppositcs, or polcs, of bipolar disordcr, as wcll as an abnormal mood
statc i n which thc two oppositcs sccm to bc combincd, a condition simply
callcd a m|xcd mccds|a|c. Thcn, in chaptcr 2, wc will scc how thc various
combinations of thcsc mood syndromcs dchnc thc dihcrcnt frms of bipolar
A word you will hcgucntly comc across in discussions of mood disor-
dcrs is acc|[pronounccd with thc acccnt on thc hrst syllablc) . To bc prccisc,
acc|rcfcrs to thc appcarancc of a pcrson's mood statc. Mccdrcfcrs to thc
paticnt's inncr cxpcricncc, whilc acc|rcfcrs to what othcrs obscrvc about a
pcrson`s mood, thc cxtcrnal signs of mood. [Psychiatrists talk of a paticnt's
ahcct bcing dcprcsscd or irritablc, and so frth. )
Thc manic statc, or morc simply man|a, is thc most cxtrcmc and dra-
matic of thc symptom clustcrs of bipolar disordcr. `Many pcrsons who havc
bipolar disordcr ncvcr havc a mll-blown manic cpisodc. 5ut sincc mania is
thc most unmistakablc and probably thc most dangcrous of thc abnormal
mood statcs associatcd with mood disordcrs, it is a good placc to start.
In thc manic statc, thc mood rcgulator switchcs into "high.' Mania
usually starts gradually and may takc wccks to dcvclop mlly. Although thc
symptoms may bc almost impcrccptiblc at hrst, thcy gradually bccomc morc
cxtrcmc, morc unplcasant, and morc unmistakably pathological [tablc I-I) .
In thc carly stagcs of mania, thc mood statc of ahcctcd pcrsons bcgins
gradually to movc "upward,' and thcy hnd thcmsclvcs hllcd with plcasant
fcclings of cxubcrancc-what a physician writing ovcr a hundrcd ycars ago
callcd "a wclling up of a scnsc of wcll bcing and an ovcrflowing of thc spir-
its.'' This hcightcncd scnsc of wcll-bcing and conhdcncc grows and cxpands
and gradually cvolvcs into cuphoria. nc bipolar paticnt dcscribcd it this
Thc world was hllcd with plcasurc and promisc, I fclt grcat. ot just
grcat, I fclt rca||ygrcat. I fclt I could do anything, that no task was too
iLVA1 i1iLVA1 ALL1 M
TzeirI- I Symptoms of mania
Mccd sym|cms
Elated, euphoric mood
Irritable mood
Ccy/|/vc (|b/n//ny) sym|cms
Feelings of heightened concentration
Accelerated thinking racing thougts")
cd/|y sym|cms
Increased energy level
Decreased need fr sleep
Erratic appetite
Increased libido
Sym|cms c{ sydcs/s
Grandiose delusions
dimcult. My mind sccmcd clcar, fbulously fcuscd, and ablc to makc
intuitivc mathcmatical lcaps that had up to that point cntircly cludcd
mc . . . . ot only did cvcrything makc pcrfcct scnsc, but it all bcgan to
ht into a marvclous kind of cosmic rclatcdncss. `
And hcrc wc conhont onc of thc many ironics of this illncss. at thc onsct
of an cpisodc of thc disordcr, it is not uncommon to fccl |c||cr than usual.
nc manic paticnt said, "If I'm ill, this is thc most wondcrml illncss I'vc cvcr
Changcs in thinking accompany thc changcs in mood. Thc fccling that
onc is thinking morc clcarly and morc rationally than usual is cspccially
common in thc carly stagcs of mania. This is an cspccially troublcsomc
symptom, sincc such a mcntal statc is not likcly to makc a pcrson suspcct
that somcthing is wrong. ot only docs thinking sccm clcarcr than usual to
thc manic paticnt, but a fccling that mcntal proccsscs arc moving[us|cr than
usual also dcvclops. At hrst thcrc may bc only a plcasant scnsc of nimblc-
ncss of thinking. Invariably, howcvcr, thinking proccsscs accclcratc. "guick`'
bccomcs "fst and hnally "racing' This vivid dcscription of such an accclcr-
ation of thinking-illustrating what psychiatrists call ]|gh| o[ |dcus-comcs
hom a collcction of paticnt accounts writtcn carly in thc twcnticth ccntury.
My thoughts ran with lightning- likc rapidity hom onc subj cct to
anothcr. All thc problcms of thc univcrsc camc crowding into my
mind, dcmanding instant discussion and solution-mcntal tclcpathy,
hypnotism, wirclcss, tclcgraphy, Christian scicncc, womcn`s rights, and
all thc problcms of mcdical scicncc, rcligion and politics.
Thoughts chascd onc anothcr through my mind with lightning
rapidity. I fclt likc a pcrson driving a wild horsc at a wcak rcin, who
darcs not usc frcc but runs] his coursc, fllowing thc linc of lcast
rcsistancc, mad impulscs rush through my brain carrying mc hrst in
onc dircction thcn in anothcr.
Racing thoughts arc a symptom so typical of mania that thc diagnosis bc-
comcs doubtml if this symptom is abscnt. This tumbling, jumblcd jumping
hom onc thought to anothcr bccomcs progrcssivcly worsc and morc un-
plcasant as thc cpisodc dcvclops.
As thc manic individual's thinking spccds up, hcr spccch docs as wcll.
Rapid or rcssurcdspccch [thc tcrm normally uscd by psychiatrists) is ncarly
always sccn in mania. Manic individuals spcak morc and morc guickly as thc
cpisodc dcvclops, attcmpting to cxprcss thc idcas that arc whirling through
thcir consciousncss at cvcr-fstcr spccds. A psychiatric tcxt hom thc bcgin-
ning of thc twcnticth ccntury mcntions onc carly rcscarchcr who actually
countcd thc numbcr of syllablcs pcr minutc spokcn by manic paticnts. Hc
fund that manic paticnts spokc I8o to zoo syllablcs pcr minutc, comparcd
with Izz to Iy o in nonmanic pcrsons.
Somctimcs thc racing thoughts and prcssurcd spccch lcad to an out-
pouring of hcnzicd writing.
I madc notcs of cvcrything that happcncd, day and night. I madc sym-
bolic scrapbooks whosc mcaning only I could dcciphcr. I wrotc a firy
talc . . . . I notcd down cryptically all that was said or donc around mc
at thc timc, with spccial rcfcrcncc to rclcvant ncws bullctins and to
j okcs which wcrc broadcast in radio programs. Thc timc, corrcct to thc
ncarcst minutc, was writtcn in thc margin. It was all vitally important.
I was convinccd that] thc major work that] would bc bascd on this
matcrial would bc accuratc, original, provocativc and of profund
signihcancc. '
Thc fcclings of cxubcrancc and ovcrconhdcncc that charactcrizc mania can
lcad to scvcral pattcrns of bchavior typical of thc manic statc. spcnding
sprccs, scxual promiscuity, and ovcrusc of alcohol and othcr intoxicating
Spcnding sprccs can bc cxtravagant and hnancially catastrophic, bc-
causc thc manic pcrson has no conccrn fr whcrc thc moncy will comc hom
to pay thc bills. Thc incrcascd scxual fcclings of this stagc of mania may
lcad to inftuations and cvcn bctrothals. nc carly psychiatric cxpcrt notcd
that "incomprchcnsiblc cngagcmcnts, also prcgnancics, arc not rarc in thcsc
statcs. I know cascs in which thc commcnccmcnt of mania] was rcpcatcdly
announccd by a suddcn cngagcmcnt.' '" Thc loss of inhibitions typical in
mania may also lcad to promiscuity as wcll as to uncharactcristic biscxual or
homoscxual bchaviors in somc pcrsons.
Wc shall cxplorc thc complcx rclationship bctwccn bipolar disordcr and
substancc abusc in chaptcr Iy . Sumcc it to say hcrc that incrcascd and un-
charactcristic usc of intoxicating substanccs is hcgucntly sccn in mania.
nc way to undcrstand this hcdonistic triad of mania-spcnding sprccs,
iLVA1 i1iLVA1 ALL1 M 11
scxual ovcractivity, and incrcascd substancc abusc-is to group thcsc bchav-
iors togcthcr as cxprcssions of an incrcasc in "motivatcd bchaviors sccn in
mania, '' an cxaggcration of thc normal drivcs toward plcasurablc goals.
Thcrc arc almost always changcs in slccping and cating habits in mania.
A dccrcascd nccd fr slccp is in fct onc of thc hrst symptoms to dcvclop in
mania-ohcn a cluc fr individuals who havc bccn manic bcfrc that an-
othcr cpisodc may bc starting. Iood intakc is usually rcduccd bccausc manic
individuals simply don't havc timc to cat. Constantly distractcd by ncw
thoughts and idcas, thcy fccl prcsscd to continuc to act, thcy just can`t sit
still long cnough to hnish a mcal. Thc cnsuing wcight loss can bc dramatic.
As thc combination of cuphoric mood and mcntal guickncss dcvclops,
thc manic individual bcgins to fccl trcmcndously sclf- conhdcnt, cvcn fcar-
lcss. This is thc so- callcd yrand|cs||y of thc manic statc. Icars of unplcasant
conscgucnccs disappcar altogcthcr, and rccklcss cnthusiasm takcs ovcr. Thc
ahcctcd pcrson may scck out ncw advcnturcs and cxpcricnccs with no rc-
gard fr thc possiblc advcrsc rcpcrcussions. This is onc of thc points at which
thc manic pcrson can bcgin to losc touch with rcality-whcn thc grandiosc
thinking lcads thc individual to start |c||cv|nythc grcat things hc fccls ca-
pablc of.
In a landmark work on bipolar disordcr that wc'll discuss in dctail in
chaptcr q, thc Ccrman psychiatrist Lmil Kracpclin rccordcd thc symptoms
and coursc of thc illncss hc callcd man|c-dcrcss|vc |nsan||y. [I also guotc
Kracpclin cxtcnsivcly hcrc and in chaptcr z. ot only did Kracpclin writc
somc of thc most vivid and cnduring dcscriptions of thc symptoms of bi-
polar disordcr, but his insights into thc dihcrcnt frms and thc coursc of thc
illncss havc provcd to bc corrcct again and again. ) Kracpclin`s dcscription of
thc grandiosc dclusions of mania, writtcn in I86, is classic.
Thc paticnt asscrts that hc is dcsccndcd hom a noblc fmily. That hc
is a gcntlcman, hc calls himsclf a gcnius, thc Lmpcror William, thc
Lmpcror of Russia, Christ, hc can drivc out thc dcvil. A paticnt sud-
dcnly cricd out on thc strcct that hc was thc Lord Cod, thc dcvil had
lch him. Icmalc paticnts posscss cighty gcnuinc diamonds, arc lcading
singcrs, lcading violinists, Quccn of 5avaria, Maid of rlcans, a firy,
thcy arc prcgnant, arc going to bc cngagcd to St. Irancis, arc to givc
birth to thc rcdccmcr . . . thc Mcssiah. ' '
Modcrn paticnts arc morc likcly to bccomc convinccd that thcy arc prcs-
idcnt or primc ministcr rathcr than king or guccn, a rock star rathcr than
a grcat violinist, but thc fcclings that lcad to such bclicfs arc thc samc. a
fntastic, indcscribablc fccling of mcntal powcr and signihcancc. Icclings
of rcligious inspiration arc vcry common. Paticnts may fccl that thcy arc a
modcrn prophct, thc fundcr of a ncw rcligion, a rcincarnation of Christ,
cvcn a ncw god.
Thc "fccling good stagc of mania is somctimcs vcry short- livcd, and thc
clatcd mood and grandiosity can bc guickly rcplaccd by an angry, irritablc
mood. Quoting Kracpclin again.
Thc paticnt is dissatishcd, intolcrant, fulthnding . . . cvcn rough. Tri-
fling cxtcrnal occasions may bring about cxtrcmcly violcnt outbursts of
ragc. In his mry, hc thrashcs his wifc and childrcn, thrcatcns to smash
cvcrything to smithcrccns . . .
. . . At thc most trifling ahront it may comc to outbursts of ragc of
cxtraordinary violcncc . . . clamorous abusc and bcllowing, to dangcr-
ous thrcats with shooting and stabbing, to blind dcstruction and actual
attacks. ' '
Somctimcs thc manic individual altcrnatcs bctwccn clation and irritability
fr a timc, but usually thc irritablc, unplcasant mood bccomcs prcdominant.
It is ohcn this irritability that brings thc paticnt to mcdical attcntion.
As thc manic statc continucs to dcvclop, prcssurcd, racing thoughts, an
incrcascd cncrgy lcvcl, and loss of inhibitions lcad to morc grossly disorga-
nizcd and disturbcd thinking and bchavior. A psychiatric tcxtbook writtcn
in thc Iyos dcscribcd this stagc as fllows.
Orivcn by grcatcr prcssurc of activity, tcrror and cxcitcmcnt, thc
manic pcrson] bccomcs violcnt, attacks his ncighbor, bcgins to shout
all kinds of accusations against his allcgcd pcrsccutors . . . . Oistortions
and] misintcrprctations . . . arc now claboratcd into dclusions of pcr-
sccution accompanicd by violcncc and panic, thc paticnt runs down
thc strcct nudc, scts hrc to thc housc, starts an argumcnt with thc
policc, shoots a gun on thc strcct or starts suddcnly to prcach thc gos-
pcl in a hcnzicd manncr . . . . If crosscd or intcrfcrcd with in any way
hc bccomcs abusivc, dcstructivc, homicidal. ''
Thinking pattcrns not only spin fstcr and fstcr but also bccomc morc bi-
zarrc. Hallucinations can dcvclop, and bclicfs callcd dc|us|cnscan occur. Thc
vcry bcst modcrn writtcn dcscriptions of thc symptoms of scvcrc mania arc
thosc of Kay Rcdhcld [amison. Or. [amison`s ncarly uniguc gualihcation to
sct thcm down is that shc is an intcrnationally rccognizcd mcdical cxpcrt on
bipolar disordcr who suhcrs hom it hcrsclf. This passagc by Or. [amison is
what I givc mcdical studcnts to rcad so that thcy can lcarn about thc symp-
toms of scvcrc mania.
Although I had bccn building up to this fr wccks and ccrtainly kncw
somcthing was scriously wrong, thcrc was still a dchnitc point whcn
iLVA1 i1 iLVA1 ALL1 M 1j
I kncw I was insanc. My thoughts wcrc so fst that I couldn't rcmcm-
bcr thc bcginning of a scntcncc halIay through. Iragmcnts of idcas,
imagcs, scntcnccs, raccd around and around in my mind likc thc tigcrs
in a childrcn's story. Iinally, likc thosc tigcrs, thcy bccamc mcaninglcss
mcltcd pools. othing fmiliar to mc was fmiliar. I wantcd dcspcr-
atcly to slow down but could not. ' `
Thcsc passagcs vividly makc thc point that thc manic statc i s not plcasant-
cvcn if it may somctimcs start out that way. Thosc unfmiliar with thc ill-
ncss somctimcs think that pcrsons with bipolar disordcr simply cxpcricncc
swings of mood bctwccn "happy and "sad' As thc frcgoing illustratcs, this
is usually not truc. Thc mll-blown manic statc is not only intcnscly unplcas-
ant but also vcry dangcrous. Thc dangcr ariscs not only hom thc incrcascd
risk of violcncc toward othcrs [or toward thc paticnt himsclf) but also hom
thc physical strcss thc syndromc causcs.
Thc combination of scvcrc manic symptoms and thc physical strcss
hom such hcnzicd hypcractivity can lcad to what Kracpclin callcd dc||r|-
cusman|a, in which thcrc is "profund clouding of consciousncss and cx-
traordinary and conmscd hallucinations . . . . Thc paticnts bccomc stupchcd,
conmscd, bcwildcrcd and complctcly losc oricntation fr timc and placc' ' "
Iortunatcly, i t i s now rarc fr a psychiatrist to scc paticnts suhcring hom
this scvcrcst frm of thc manic statc, but in Kracpclin`s timc and cvcn morc
rcccntly, mania had a signihcant mortality ratc. Pcrsons with mania dicd "in
a statc of progrcssivc cxhaustion,`' suhcring dchydration and cardiovascu-
lar collapsc.
In Ij, just as lithium, thc hrst chcctivc trcatmcnt fr bipolar disordcr,
was bccoming availablc, a study hom thc ational Institutcs of Hcalth at-
tcmptcd to dcscribc a typical manic cpisodc hom bcginning to cnd. Paticnts
who had bccn admittcd to a rcscarch unit that was trying to hgurc out how
to usc lithium safcly and chcctivcly fr thc trcatmcnt of bipolar disordcr
wcrc carcmlly obscrvcd. Thc coursc of thcir symptoms was mcticulously
documcntcd and dcscribcd. Thc authors concludcd that thrcc stagcs could
bc dcscribcd in a manic cpisodc.
Stagc I] . Incrcascd psychomotor activity which includcd incrcascd . . .
ratc of spccch and incrcascd physical activity . . . . Luphoria prcdomi-
natcd, although irritability bccamc obvious whcn thc paticnts' many
dcmands wcrc not instantly satishcd . . . . Lxpansivcncss, grandiosity
and ovcrconhdcncc wcrc obscrvcd] . Thoughts wcrc cohcrcnt though
somctimcs disconncctcd] . Also hcgucntly obscrvcd during this stagc
wcrc incrcascd scxuality or scxual prcoccupations, incrcascd intcrcst
in rcligion, incrcascd and inappropriatc spcnding of moncy, incrcascd
smoking, tclcphonc usc and lcttcr writing. Somc of thc paticnts wcrc
awarc of thc mood changc on somc lcvcl and dcscribcd thc fccling of
"going high,' having racing thoughts and fccling likc thcy wcrc in an
airplanc. At this stagc thc paticnts wcrc not out of control.
Stagc II] . Prcssurc of spccch and . . . activity incrcascd still mrthcr.
Mood, although cuphoric at timcs, was now morc promincntly char-
actcrizcd by incrcasing unplcasantncss] . . . . Thc irritability obscrvcd
initially had progrcsscd to opcn hostility and angcr, and thc accompa-
nying bchavior was hcgucntly assaultivc. Racing thoughts progrcsscd
to . . . incrcasing disorganization. Prcoccupations that wcrc prcscnt
carlicr bccamc morc intcnsc with carlicr . . . grandiosc trcnds now
apparcnt as hank dclusions.
Stagc III] . A dcspcratc, panic strickcn, hopclcss statc cxpcricnccd by
thc paticnt as clcarly unplcasant] , accompanicd by hcnzicd and hc-
gucntly cvcn morc bizarrc . . . activity. Thought proccsscs that carlicr
had bccn only dimcult to fllow now bccamc incohcrcnt . . . . Oclusions
wcrc bizarrc . . . . Hallucinations wcrc prcscnt in about onc- third of thc
paticnts] . '
Morc rcccntly somc rcscarchcrs havc gucstioncd whcthcr typical manic
cpisodcs includc all of thcsc stagcs. Spccihcally, somc rcscarchcrs bclicvc
that Stagc III mania [or dysbcr|cman|a,as it has comc to bc callcd) occurs
only in a subgroup of paticnts with bipolar disordcr. Thcrc is somc cvidcncc
that thcsc paticnts havc a variant of thc disordcr and may nccd mcdications
dihcrcnt hom what othcrs with a morc typical bipolar disordcr would nccd.
[Morc on this in "Mixcd Statcs,' latcr in this chaptcr. ) cvcrthclcss, this study
on thc "stagcs of mania`' was important bccausc its invcstigators uscd mod-
crn clinical mcthods to documcnt how sick paticnts with mania can gct.
Lvcn morc important, it madc thc rcscarchcrs rcalizc that it would bc casy
to misdiagnosc a vcry disorganizcd paticnt in Stagc III mania as having
schizophrcnia, a psychiatric illncss that rcguircs a vcry dihcrcnt trcatmcnt
approach and has a dihcrcnt prognosis hom bipolar disordcr.
In I88I a Ccrman psychiatrist namcd Mcndcl publishcd a book about
thc manic statc callcd D|cMan|c and in it proposcd that anothcr tcrm bc
uscd fr statcs of mildcr cuphoria and hypcractivity that did not progrcss
to mll-blown mania. Hc callcd this condition bycman|a, "similar to thc
statc of cxultation in typical mania but] with a ccrtain lcsscr gradc of dcvcl-
opmcnt' '' [Thc prchx byc- comcs hom a Crcck word mcaning "undcr')
Hypomania can bc thought of as having only thc symptoms prcscnt at thc
iLVA1 i1 iLVA1 ALL1 M 1j
bcginning of a manic cpisodc [Stagc I in thc study dcscribcd abovc) . thc
clatcd mood, thc incrcascd cncrgy lcvcl, thc rapid thinking and spcaking,
and somctimcs a bit of thc irritability. orman Lndlcr, anothcr psychologist
who himsclf suhcrcd hom a mood disordcr and wrotc of his cxpcricnccs
with thc illncss, dcscribcd hypomania this way. "Most of thc timc I was
busy, busy, busy, taping rccords, playing tcnnis, skiing, writing manuscripts,
talking . . . rcading, going to movics, staying up at night, waking up carly in
thc morning, always on thc go-busy, busy, busy. Iurthcrmorc, I was boast-
ing about all thc cncrgy I had that cnablcd mc to kccp up this fst pacc . . . .
Instcad of occasionally `idling' in ncutral I was always in ovcrdrivc''"
Although pcrsons in thc hypo manic stagc do not havc thc scvcrc mcntal
disorganization of mania and arc by dchnition not agitatcd and hcnzicd to
thc point of violcncc toward thcmsclvcs or othcrs, hypomania can ncvcr-
thclcss havc unplcasant conscgucnccs. Icclings of incrcascd conhdcncc can
lcad to folish invcstmcnts in rcal cstatc or thc stock markct, and paticnts
can sguandcr pcrsonal rcsourccs on grandiosc and risky busincss vcnturcs.
Incrcascd scxual fcclings can lcad to cxtramarital ahairs or promiscuity-
actions that can bc lifc-thrcatcning in thc agc of HIV discasc. Thc irritability
of hypomania can lcad to argumcnts and disagrccmcnts with fmily, col-
lcagucs, or ncighbors that can sour rclationships, somctimcs irrcparably. Or.
Lndlcr dcscribcd it this way.
As a hypomanic, I didn't stop to analyzc my thoughts, fcclings, or
bchavior. I was much too busy and didn`t always stop to think about
what I was doing . . . . I was critical of othcrs and occasionally told
somc pcoplc oh publicly. I was not so conccrncd about . . . thc chcct
my bchavior had on othcrs] . I was aggrcssivc, talkcd inccssantly, and
intcrruptcd othcrs whilc thcy wcrc spcaking. Whcncvcr I had a thought
I fclt compcllcd to uttcr it, and I didn't always ccnsor my thoughts and
fcclings. At timcs I sccmcd to havc lost my scnsc of judgmcnt. I was
having a good timc, I was narcissistically prcoccupicd with mysclf, but
[without bcing awarc of it) I was making my wifc miscrablc. ''
Pcrsons with cvcn mild hypomania can guit a good j ob in a burst of ovcr-
conhdcncc or irritability, withdraw thcir lifc savings fr a gct-rich- guick
schcmc, or simply bcgin to drivc thcir car too fst-all bchaviors with po-
tcntially dcvastating conscgucnccs.
Words likc scduc||vcand add|c||vcarc hcgucntly applicd to thc hypo-
manic syndromc. 5ccausc individuals i n a hypomanic statc fccl so good,
thcy scldom scck trcatmcnt. Lvcn fr pcrsons who havc a history of prcvious
manic or dcprcssivc cpisodcs of bipolar disordcr and pcrhaps should know
that troublc is brcwing, thc giddy dclight of bcing hypomanic ohcn sccms
TzeirI-2 Lcngth of timc bcfrc hospitalization fr mania in nincq-fur
manic paticnts
Pcrccn|ayc c{ a|/cn|s
1/mc Ma|c Icma|c
1q-Odays 6 6z
months 11 11
6 months 11 1O
1 ycar or morc 6 1
Scurce Oata hom Gcorgc Wnokcr, Man|a and Deress|cn A C|assqca||cn c) S)ndrcme and
D|sease baItmorc: [ohns Iopkns Lnvcrsty Ircss, tt), t.
Nc|e otcc that somc patcnts havc symptoms r many months bcrc rcccvng nccdcd
trcatmcnt. Ourng ths tmc, hypomanc symptoms can wrcak havoc on thcr Ivcs.
too dclicious to intcrrupt. Pcrsons whosc abnormal mood statcs arc succcss-
mlly controllcd with mcdication somctimcs stop trcatmcnt to rccapturc thc
wondcrml fcclings that accompany hypomania.
5ccausc hypomanic individuals arc nc|psychotic, thcy ohcn cannot bc
involuntarily trcatcd fr thcir illncss, bccausc critcria fr involuntary trcat-
mcnt insist upon "dangcrous bchaviors. [Wc shall discuss involuntary trcat-
mcnt in chaptcr 22. ) Hypomanic pcrsons can avoid trcatmcnt fr wccks,
cvcn months [tablc I-2), conscgucntly ruining thcir hnancial status, crcdit
rating, cmploymcnt history, rclationships, and hcalth.
As wc shall scc in a latcr scction, many paticnts go through cpisodcs of
hypomania only and ncvcr bccomc complctcly manic. thcrs havc both hy-
pomanic and manic cpisodcs. bscrvations about thc hcgucncy and intcn-
sity of hypomanic vcrsus manic cpisodcs in dihcrcnt individuals arc bcgin-
ning to suggcst that thc classic "manic- dcprcssivc disordcr with cpisodcs
of mll-blown mania and dcprcssion may bc only onc of many frms of thc
illncss. [Wc shall discuss this ncw way of thinking about bipolar disordcr in
chaptcr 2, in thc scction "5ipolar Spcctrum Oisordcrs')
Thc Syndromc ot cprcsson
Tc dcprcssion of bipolar disordcr is both casicr and morc dimcult to
dcscribc and discuss than mania or hypomania. It is casicr to discuss bc-
causc dcprcssion is a morc familiar sct of fcclings. cvcryonc, whcthcr suf-
fcring hom bipolar disordcr or not, has gonc through pcriods of dcprcsscd
mood. 5ut thc dcprcssivc syndromc of bipolar disordcr is morc dimcult to
discuss fr that vcry rcason. it is a vcry dihcrcnt cxpcricncc hom "normal
iLVA1 i1 iLVA1 ALL1 M 1,
TzeirI- Symptoms of dcprcssion
Mccd sym|cms
Depressed mood
Dysphoric mood
Diurnal variation of mood early-morning
depression, mood improving as day
goes on)
Guilty feelings
Loss of ability to feel pleasure anhedonia)
Social withdrawal
Suicidal thougts
Ccy/|/vc (|b/n//ny) sym|cms
Poor concentration
Poor memory
Slowed thinking
cd/|y sym|cms
Sleep disturbance.
Appetite disturbance.
weight loss
weight gain
Loss of interest in sex
Worsening of painml conditions
Sym|cms c{ sycbcs/s
Delusional thinking
Catatonic states
dcprcssion. In modcrn psychiatric tcrminology, this abnormal dcprcsscd
mood statc is callcd ma)crdcrcss|cnor somctimcs c||n|ca|dcrcss|cn[tablc
I- ) .
Whcn pcrsons who do not suhcr hom a mood disordcr go through a pc-
riod of low mood, such as ahcr a romantic disappointmcnt, thc loss of a job,
or a pcriod of homcsickncss, not only is thcir dcprcsscd mood tcmporary,
but thcy rctain thc normal rcac||v||y of mood. Anyonc who has attcndcd
a mncral and thcn rcturncd to thc homc of thc bcrcavcd ahcrward has
probably obscrvcd this normal rcactivity of mood, pcrhaps cvcn in hcrsclf.
Mourncrs who might havc bccn gricf-strickcn during thc mncral scrvicc or
at thc gravc sitc can ahcrward ohcn rclax, rcminiscc about good mcmorics
of thc pcrson who has dicd, and cnjoy catching up with hicnds and rclativcs
whom thcy may not havc sccn fr a long timc. Thc rcactivity of mood is also
rctaincd in thc loncly or homcsick pcrson who gocs to thc movics and loscs
himsclf in a good hlm. Wc arc ablc to dispcl thc fcclings of bcrcavcmcnt, iso-
lation, or disappointmcnt-cvcn i f it's only fr a fcw hours-if thc dcprcsscd
mood is a "normal onc.
Thc most signihcant fcaturc of thc dcprcsscd mood in thc syndromc of
dcprcssion is that instcad of bcing rcactivc, thc mood is ccns|r|c|cd. Ycars
ago AM radio stations uscd to givc away hcc radios, gihs that camc with
only onc catch. thcy couldn't bc tuncd to any of thc sponsoring station's
compctitors. Thcsc radios wcrc built to rcccivc only thc signal of thc station
that gavc thcm away. Thc mood statc of thc pcrson who is suhcring through
a dcprcsscd cpisodc of bipolar disordcr is likc onc of thosc radios, "sct to
rcccivc only onc mood signal. dcprcssion. Thc mood of thc syndromc of
dcprcssion is a rclcntlcss, pcrvasivc gloom that continucs hom onc day to
thc ncxt and hom which thc amictcd pcrson cannot rousc hcrsclf. As Pulit-
zcr Prizc-winning novclist William Styron said of his own dcprcssion, " Thc
wcathcr of dcprcssion i s unmodulatcd, its light a brownout'''
In thcsc constrictcd-mood statcs, dcprcsscd individuals hnd thcir think-
ing dominatcd by thoughts of sadncss and loss, rcgrct and hopclcssncss.
Cuilty ruminations arc cspccially charactcristic of thc syndromc of dcprcs-
sion, and psychiatrists ohcn makc a spccial point to ask about guilty fcclings
whcn thcy cxaminc a pcrson bcing cvaluatcd fr dcprcssion. Ruminations
on thcmcs of guilt, shamc, and rcgrct arc common in thc dcprcsscd statcs
of thc mood disordcrs, but thcy arc uncommon in thc "normal dcprcsscd
mood. Pcrsons cxpcricncing thc normal dcprcsscd mood that comcs ahcr a
pcrsonal loss attributc thcir bad fcclings to thc fct that a loss has occurrcd,
only in unusual circumstanccs will thcy fccl that thcy arc to blamc fr thcir
problcm and bc prcoccupicd by guilty fcclings or fcclings of shamc. Thc in-
dividual with a dcprcssivc syndromc, howcvcr, hcgucntly fccls to blamc fr
his troublcs, and somctimcs fr othcr pcoplc's troublcs as wcll. Thc prcscncc
of guilty prcoccupations is vcry signihcant fr making a diagnosis of thc
syndromc of dcprcssion.
Icclings of inadcguacy and worthlcssncss arc similarly signihcant and
cspccially common in thc syndromc of major dcprcssion. Psychologist or-
man Lndlcr dcscribcd how dcprcssion causcd him to bc tormcntcd by fccl-
ings of incompctcncc cvcn at thc hcight of a succcssml acadcmic carccr.
Whcn I bccamc dcprcsscd] I was positivc I was a haud and a phony
and that I didn't dcscrvc my Ph. O. I didn't dcscrvc to havc tcnurc, I
didn't dcscrvc to bc a Iull Profcssor, I didn't dcscrvc to bc a Icllow of
thc Amcrican Psychological Association and thc Canadian Psycho-
logical Association, I didn't dcscrvc thc rcscarch grants I had bccn
awardcd, I couldn't undcrstand how I had writtcn thc books and j our-
nal articlcs that I had and how thcy had bccn acccptcd fr publication.
I must havc conncd a l ot of pcoplc. ''
Anothcr typical symptom of major dcprcssion is thc loss of intcrcst in
usually plcasurablc activitics. This can bc undcrstood as anothcr aspcct of
thc loss of normal rcactivity of mood. Thc dcprcsscd pcrson is unablc to
dcrivc any plcasurc hom listcning to music, going to a movic, cngaging in
thc sports or hobbics that usually providc cnj oymcnt. This loss of thc ability
to fccl plcasurc has comc to bc callcd anbcdcn|a [dcrivcd hom thc Crcck
word fr "plcasurc) . In [ohann Wolfgang von Cocthc's novcl 7cScrrcwsc}
iLVA1 i1 iLVA1 ALL1 M 1
cunyWcr|bcr thc main charactcr cxprcsscs a loss of rcsponsivcncss to thc
j oys and bcauty of naturc. "aturc lics bcfrc mc as immobilc as in a littlc
lacgucrcd painting, and all this bcauty cannot pump onc drop of happincss
hom my hcart to my brain''' Paticnts say that fod has lost its tastc, thc
colors havc draincd away hom sunriscs and landscapcs, and flowcrs havc
lost thcir tcxturcs and pcrmmcs-cvcrything has bccomc bland, dull, and
Ior somc, thc bright and bcautiml things of thc world arc a sourcc of
anguish rathcr than plcasurc. Thc ninctccnth- ccntury Austrian composcr
Hugo Wolf dcscribcd a tcrriblc scnsc of sorrowful isolation during his dc-
prcssions, a fccling of scparation hom thc world of ordinary plcasurcs-all
thc morc painml whcn it occurrcd in springtimc.
What I suhcr hom . . . I am guitc unablc to dcscribc. This wondcrml
spring with its sccrct lifc and movcmcnt troublcs mc unspcakably.
Thcsc ctcrnal bluc skics, lasting fr wccks, this continuous sprouting
and budding in naturc, thcsc coaxing brcczcs imprcgnatcd with spring
sunlight and hagrancc of flowcrs . . . makc mc hantic. Lvcrywhcrc this
bcwildcring urgc fr lifc, huitmlncss, crcation-and only I . . . may
not takc part in this fcstival of rcsurrcction, at any ratc not cxccpt as a
spcctator with gricf and cnvy. '`
[ust as thc manic syndromc inmscs thc ahcctcd pcrson with fcclings of in-
cxprcssiblc joy, thc syndromc of dcprcssion brings indcscribablc anguish.
Many individuals who havc suhcrcd hom dcprcssion havc strugglcd to dc-
scribc thc fcclings, and cvcn grcat writcrs sccm to fltcr in thc attcmpt. Wil-
liam Styron said, "If thc pain wcrc rcadily dcscribablc most of thc countlcss
suhcrcrs hom this ancicnt amiction would havc bccn ablc to conhdcntly
dcpict . . . thcir tormcnt. Hcalthy pcoplc cannot] imaginc a frm of tor-
mcnt so alicn to cvcryday cxpcricncc. Ior mysclf, thc pain is most closcly
conncctcd to drowning or suhocation-but cvcn thcsc imagcs arc oh thc
Somctimcs thc "indcscribablc mcntal discomfrt sccn in maj or dcprcs-
sion is a fccling that sccms dihcrcnt hom thc sad, pcssimistic mood pcoplc
usually mcan by thc word dcrcss|cn. Instcad, pcoplc with major dcprcssion
may havc a tcnsc, irritablc, miscrablc sort of mood callcd dysbcr|a. [Rc-
mcmbcr that thc tcrm dysbcr|cman|ais uscd to dcscribc a tcnsc, unplcas-
ant, irritablc mood that can bc sccn along with thc agitation and hypcractiv-
ity of thc manic statc. )
Thc changcs in thinking and physical wcll-bcing causcd by thc syn-
dromc of dcprcssion arc pcrhaps casicr to dcscribc. nc's cncrgy lcvcl and
thinking as wcll as mood arc ahcctcd-in an oppositc dircction of polarity
hom that sccn in mania. Thc dcprcsscd pcrson cxpcricnccs slowing and in-
cmcicncy in thinking and a fccblcncss of mcmory and conccntration. Infr-
mation-proccssing and rcasoning fltcr, and simplc dccisions can bccomc
ovcrwhclming dilcmmas. Lndlcr cxprcsscd it this way. "My indccisivcncss
was thc worst of all. I couldn't dccidc what to cat or what to wcar. I couldn't
dccidc whcthcr to gct out of bcd or to stay. I couldn't dccidc whcthcr to
showcr or not to showcr. I could ncvcr dccidc what to do bccausc I didn't
know mysclf.''
Thcsc ccyn|||vcmnctions [hom thc Latin ccycsccrc,mcaning "to know)
bccomc progrcssivcly dcbilitatcd as thc dcprcssion dccpcns, but cvcn in
mildcr dcprcssions, ordinary mcntal tasks sccm to rcguirc cxtraordinary cf-
frt. Kracpclin dcscribcd thc scvcrc cognitivc slowing hc obscrvcd in his
scvcrcly dcprcsscd paticnts. " Thc paticnt's] thoughts arc as if paralyscd . . .
immobilc. Hc is no longcr ablc to pcrccivc or to fllow thc train of thought
of a book or convcrsation . . . . Hc has no mcmory, hc has no longcr com-
mand of knowlcdgc frmcrly fmiliar to him and] must considcr a long
timc about simplc things'' In thc cldcrly, thcsc sorts of thinking problcms
can bc so scvcrc that dcprcssion is misdiagnoscd as Alzhcimcr's discasc.
Scvcrc dcprcssion almost always causcs a changc in thc pcrson's slccping
pattcrn. Ocprcsscd pcrsons hcgucntly suhcr hom insomnia-but also hom
its oppositc, slccping too much bycrscmn|ais thc tcchnical tcrm) . In thc
dcprcssion associatcd with bipolar disordcr, hypcrsomnia sccms cspccially
common, pcrhaps morc common than in othcr typcs of clinical dcprcssion,
whcrc insomnia prcdominatcs .
Somctimcs dcprcsscd pcrsons havc a pcculiar rhythmic pattcrn of slccp
disturbancc and mood changcs throughout thc day, callcd d|urna|var|a||cn
c}mccd d|urna|is a word uscd in biology to rcfcr to a twcnty-fur-hour
cyclc) . It causcs pcrsons to fll aslccp at thc usual timc and without much
dimculty but wakc up vcry carly in thc morning ahcr only a fcw hours of
slccp. Lying awakc hours bcfrc sunrisc, thcy cxpcricncc thcir lowcst mood
of thc day, and minor problcms and rcgrcts sccm magnihcd and ovcrwhclm-
ing during this carly- morning pcriod. I rccall onc paticnt who told mc that
during thosc carly- morning hours, "I lic awakc thinking about cvcry stupid
thing I'vc cvcr donc in my lifc' Amcrican author I. Scott Iitzgcrald, who
dcscribcd his strugglcs with dcprcssion in thc I 6 autobiographical work
7c Crac/u, gavc a vivid account of this mood pattcrn. Hc cxpcricnccd
thc worst of his moods during thc prcdawn hours, rccalling that "at thrcc
o'clock in thc morning, a frgottcn packagc has thc samc tragic importancc
as a dcath scntcncc' Ior Iitzgcrald, thcsc nocturnal agonics wcrc thc nadir
of his dcprcssions, which hc callcd "thc dark night of thc soul''' Individuals
noticc a gradual lihing of thcir mood as sunrisc approachcs, and whcn thc
morning dawns, thcy can ohcn rousc thcmsclvcs and start thcir daily activi-
tics. As thc day gocs on, thcir mood continucs to improvc littlc by littlc, until
iLVA1 i1 iLVA1 ALL1 M 21
by day's cnd thcy fccl ncarly back to normal. Thcy go to bcd and usually fll
aslccp normally, but scvcral hours latcr, it's "thrcc o'clock in thc morning
again. thcy awakcn dcprcsscd, and thc cyclc rcpcats itsclf.
ovclist William Styron cxpcricnccd a vcry striking diurnal variation
in his mood during his dcprcssion, but with a rcvcrsal of thc usual pattcrn.
"Whilc I was ablc to risc and mnction almost normally during thc carlicr
part of thc day, I bcgan to scnsc thc onsct of thc symptoms at mid- ahcrnoon
or a littlc latcr-gloom crowding in on mc, a scnsc of drcad and alicnation
and . . . stifling anxicty' '"
Thc disruptions of various bodily rhythms that occur in dcprcssion and
mania havc convinccd many scicntists that somc pcrsons with mood dis-
ordcrs havc a disturbancc of thcir cbrcnc||c|cg [hom cbrcncs, thc Crcck
word fr "timc) . Pcrsons with mood disordcrs havc bccn obscrvcd to havc
disturbanccs in thc normal rhythmic pulsing of various hormonc lcvcls, in
body tcmpcraturc fluctuations, in thc slccp-wakc cyclc, and in othcr natural
rhythms. Latcr in this book wc shall cxaminc conncctions bctwccn thcsc
natural rhythms and mood and also look at othcr cyclcs. thc monthly cyclcs
of mood in womcn with prcmcnstrual mood symptoms [chaptcr I() and thc
twclvc-month cyclcs of pcrsons with scasonal ahcctivc disordcr [chaptcr I6) .
Appctitc i s also usually disturbcd in dcprcsscd individuals. As with slccp
problcms, changcs occur in both dircctions, and paticnts may cat too much
or too littlc. Thcy may losc or gain a signihcant amount of wcight during
pcriods of dcprcssion. As might bc cxpcctcd, thc dcprcsscd pcrson loscs in-
tcrcst in scx, this symptom is pcrhaps bcst undcrstood as part of thc pcrson's
inability to cxpcricncc plcasurablc activitics of any kind, thc "anhcdonia of
f thc othcr bodily symptoms that occur in dcprcssion, onc of thc most
striking is a scnsc of ftiguc with promincnt low cncrgy and listlcssncss.
As Lndlcr put it. " My] ftiguc was] cxtrcmc to thc point of cxhaustion.
I was too tircd to makc dccisions and fclt as if I had a hugc wcight on my
back that wouldn't allow mc to achicvc anything . . . . o mattcr how long I
staycd in bcd and slcpt I ncvcr fclt rcstcd and rchcshcd . . . . Whcn I did gct
out of bcd I was lcthargic. I was slow as molasscs''' Hcadachcs, constipa-
tion, and a fccling of hcavincss in thc chcst arc common, as arc othcr morc
dimcult-to- dcscribc scnsations of physical discomfrt. Styron said. "I fclt
a kind of numbncss, an cncrvation . . . an odd hagility-as if my body had
actually bccomc hail, hypcrscnsitivc and somchow disj ointcd and clumsy.
othing fclt guitc right. . . . Thcrc wcrc twitchcs and pains, somctimcs in-
tcrmittcnt, ohcn sccmingly constant, that sccmcd to prcsagc all sorts of dirc
inhrmitics' ''
It is not clcar whcthcr thcsc symptoms arc causcd by dcprcssion itsclf or
arisc hom thc lack of rcstml slccp, thc lack of cxcrcisc, and thc poor cating
habits that dcprcssion brings on. Pcrsons who havc prccxisting painml mcd-
ical conditions such as arthritis or inflammatory bowcl discasc arc usually
morc bothcrcd by thc physical symptoms of thcsc illncsscs whcn thcy arc
dcprcsscd. Thc conncctions bctwccn dcprcssion and problcms with ftiguc
sccn in chronic ftiguc immunodchcicncy syndromc and thc painml j oint
and musclc discasc hbromyalgia arc wcll known but poorly undcrstood. Oc-
prcssion sccms to lowcr thc pain thrcshold. dcprcsscd individuals arc morc
scnsitivc to pain and arc morc distrcsscd by it.
Somc pcrsons may bc willing to scck trcatmcnt fr thcsc physical symp-
toms but rcluctant to mcntion thcir mood problcms . So somctimcs paticnts
with dcprcssion cnd up gctting all kinds of tcsts and trcatmcnts fr physical
illncsscs hom thcir physicians, whcn thcir rcal problcm is dcprcssion.
[ust as in thc syndromc of mania, pcrsons suhcring through an cpi-
sodc of thc dcprcssion of bipolar disordcr can cxpcricncc thc distortions of
thinking that psychiatrists call dc|us|cns. As thcir vicw of thc world and of
thcmsclvcs bccomcs incrcasingly colorcd by thcir pcrvasivc mood changcs,
dcprcsscd individuals can comc to bclicvc that tcrriblc things arc happcning
all around thcm. "I was positivc that I was going to bc hrcd hom thc uni-
vcrsity bccausc of incompctcncc and that my fmily] would bccomc dcs-
titutc-that wc would go brokc,' wrotc Lndlcr. "I fclt guilty at thc prospcct
of not bcing ablc to support my fmily' '' In addition to such dc|us|cnsc}
cvcr|y, dclusions can arisc hom thc uncomfrtablc physical scnsations of
dcprcssion. Paticnts bclicvc thcy havc canccr, AIOS, or somc othcr tcrriblc
Kracpclin dcscribcd thc incrcasingly bizarrc byccbcndr|aca|dc|us|cns
hc somctimcs obscrvcd in his paticnts. " Thc paticnt bclicvcs hc is] incur-
ably ill, half- dcad, no longcr a right human bcing, has lung discasc, a tapc-
worm, canccr in his throat, cannot swallow, docs not rctain his fod . . . .
Iacc and hgurc havc changcd, thcrc is no longcr blood in his brain, hc docs
not scc any longcr, must bccomc crazy, rcmain his wholc lifctimc in an in-
stitution, dic, has alrcady dicd.' Paticnts with such bclicfs may rcmsc to cat
or drink, convinccd that thcir body cannot absorb thc fod. Paranc|ddc|u-
s|cns,bclicfs that onc is in dangcr or thc victim of cvil pcoplc and frccs, can
also occur.
Lvcrywhcrc dangcr thrcatcns thc paticnt. . . . Strangc pcoplc arc in thc
housc, a suspicious motorcar drivcs past. Pcoplc mock him, arc going
to thrash him, to chasc him hom his post in a shamcml way, incarccr-
atc him, bring him to justicc, cxposc him publicly, dcport him, throw
him into thc hrc, drown him. Thc pcoplc arc alrcady standing outsidc,
thc bill of indictmcnt is alrcady writtcn, thc scahold is bcing put up,
hc must wandcr about nakcd and miscrablc . . . . His rclativcs also arc
iLVA1 i1 iLVA1 ALL1 M 2j
bcing torturcd . . . . His fmily is imprisoncd, his wifc has drowncd hcr-
sclf, his parcnts arc murdcrcd, his daughtcr wandcrs about in thc snow
without any clothcs on. ''
It's casy to undcrstand why suicidal thinking and bchavior arc so common
in thc syndromc of major dcprcssion. comparcd with thc horrors of such dc-
lusional imaginings, dcath may sccm a wclcomc altcrnativc. It's also possiblc
to undcrstand why dclusionally dcprcsscd pcrsons can occasionally bc dan-
gcrous to othcrs as wcll as to thcmsclvcs. thcy can comc to bclicvc that thosc
closc to thcm arc in similar dangcr of grucsomc pcrsccution and would bc
bcttcr oh dcad.
Ha||uc|na||cns occur in scvcrc dcprcssion, but not as hcgucntly as in
mania [tablc I-(). Thc hallucinations arc consistcnt with thc mood and arc
hightcning, cvcn horrifying. " Thc paticnts scc cvil spirits, dcath, hcads of
animals . . . crowds of monstcrs . . . dcad rclativcs . . . . Thc paticnt hcars his
torturcd rclativcs scrcaming and lamcnting . . . . His fod tastcs of soapy watcr
or cxcrcmcnt, of corpscs and mildcw''`
Somc scriously ill paticnts sink into a statc of lcthargy and dcspair that
is callcd dcrcss|vcs|ucr. Styron's dcscription of this horriblc condition is
thc bcst I havc cvcr rcad.
I had now rcachcd that phasc of thc disordcr whcrc all scnsc of hopc
had vanishcd, along with thc idca of a mturity, my brain . . . had
bccomc lcss an organ of thought than an instrumcnt rcgistcring, min-
utc by minutc, varying dcgrccs of its own suhcring . . . . I'd fccl thc
horror, likc somc poisonous fg bank, roll in upon my mind, frcing
mc to bcd. Thcrc I would lic fr as long as six hours, stuporous and
virtually paralyzcd, gazing at thc cciling. '"
TzeirI-| Oclusions and hallucinations in bipolar disordcr.
Mania vcrsus dcprcssion
Ca|cycry c{ sym|cms
Pcrccn|ayc c{ a|/cn|s
Scurce Oata hom O. WbIack and A. asrallah, "Iallucnatons and OcIusons n ,;
Iatcnts wth Lnpolar and bpoIar Ahcctvc Osordcrs, Pchca|hc|cy) zz 8): z8-jq.
[ust as fcw modcrn psychiatrists havc cvcr sccn thc most cxtrcmc stagc
of mania, so- callcd dc||r|cusman|a, it is also frtunatcly rarc today to scc a
paticnt dcprcsscd to thc point of unrcsponsivcncss and immobility that psy-
chiatrists call ca|a|cn|a. Kracpclin, dcscribing paticnts in an cra whcn virtu-
ally no trcatmcnt was availablc fr this tcrriblc condition, starkly dcscribcs
this dccpcst abyss of dcprcssion. "Thc paticnts lic in bcd taking no intcrcst in
anything. Thcy bctray no pronounccd cmotion, thcy arc mutc, inacccssiblc,
thcy pass thcir bowcl movcmcnts] undcr thcm, thcy starc straight in hont
of thcm with a] vacant cxprcssion of countcnancc likc a mask and with
widc opcn cycs` '
Llcctroconvulsivc thcrapy [LCT), discusscd in morc dctail in chaptcr Io,
is a vcry chcctivc trcatmcnt fr thcsc cxtrcmc statcs of thc dcprcssivc syn-
dromc. Although thcrc havc bccn misguidcd attcmpts to ban this safc and
chcctivc trcatmcnt tcchniguc in thc Lnitcd Statcs, and cgually misguidcd
activists still occasionally appcar in thc mcdia to disparagc it, LCT frtu-
natcly rcmains availablc to trcat this most cxtrcmc stagc of dcprcssion, rcs-
cuing thcsc individuals hom a kind of living hcll.
Mxcd Statcs
Anothcr typc of abnormal mood can bc sccn in bipolar disordcr. This
mood, a strangc combination of both thc hcnzicd intcnsity of mania and
thc horrors of dccp dcprcssion, has bccn callcd a m|xcds|a|c[somctimcs it's
tcrmcd m|xcd acc||vcs|a|c). Kay [amison dcscribcd it as thc most tcrriblc
cxprcssion of thc illncss fr hcr. "n occasion, thcsc pcriods of total dcspair
would bc madc cvcn worsc by tcrriblc agitation. My mind would racc hom
subj cct to subj cct, but instcad of bcing hllcd with . . . cxubcrancc and cosmic
thoughts . . . it would bc drcnchcd in awful sounds and imagcs of dccay and
dying, dcad bodics on thc bcach, charrcd rcmains of animals, toc- taggcd
corpscs in morgucs' '
Although psychiatrists do not yct agrcc on thc dchning charactcristics
fr this mood statc, thcy havc long rccognizcd that symptoms of dcprcssion
and mania sccm to cxist almost simultancously in somc paticnts [tablc I- y ) .
This statc rcprcscnts a distinct varicty of abnormal mood that i s scparatc
hom dcprcssion and typical mania yct combincs fcaturcs of both. Thc ac-
cclcratcd thinking and hypcractivity typical of thc manic statc rcmain its
most striking fcaturcs, but instcad of a cuphoric mood, thcsc changcs bc-
comc combincd with a dcprcsscd, dcspairing, dcspcratc mood. Kracpclin
dcscribcd paticnts with "flight of idcas, cxcitcmcnt and anxicty who wcrc
at thc samc timc "anxiously dcspairing' '' thcr labcls uscd fr thc mixcd
statc arc "mixcd mania and "dysphoric mania''" As wc shall scc in chaptcr
iLVA1 i1 iLVA1 ALL1 M 2j
TzeirI- Symptoms in tcn paticnts wth mixcd mania [dysphoric mania)
Sym|cms Pcrccn|ayc c{ a|/cn|s
Depressed mood 1OO
Irritable mood 1OO
Increased activity 1OO
Pressured speech
Hostility ;
Flight of ideas |
Anxiety attacks |
Delusions depressive)
Delusions nondepressive) z:
Scurce Oata hom Frcdcrck K. Goodwn and Kay KcdhcId [amson, Man|c-Deress|ve I||ness
cw York: Oxrd Lnvcrsty Ircss, o ), q.
2, thcrc is somc cvidcncc that this mood statc docs not occur in all paticnts
with bipolar disordcr and that, whcn it docs occur, a dihcrcnt trcatmcnt
approach is ncccssary.
[ust as mll-blown mania is unmistakablc, so is a mll-blown mixcd statc.
5ut in thc samc way that a statc of mild hypomania can bc dimcult to dis-
tinguish hom an clcvatcd but normal mood, mildcr mixcd statcs can bc
dimcult t o rccognizc. A mild mixcd statc somctimcs lasts only a fcw hours.
Whcncvcr a paticnt tclls mc about bcing troublcd by uncomfrtablc angry
"ragcs,' I suspcct that hc may bc having mild mixcd statcs. "Anxicty is an-
othcr word that pcrsons cxpcricncing this mood statc usc to dcscribc it, al-
though it is not thc fcarml hctmlncss of ordinary anxicty, this statc is morc
likc a prcssurc cookcr mll of dcprcsscd cmotions rcady to cxplodc.
Tc mixcd statc is vcry dangcrous bccausc thc paticnt has ncgativc, dc-
prcssing thought pattcrns togcthcr with cxccss cncrgy, rcstlcssncss, and an
inncr scnsc of prcssurc and tcnsion. Tis ncgativc cncrgy puts paticnts in
mixcd statcs at high risk fr hurting thcmsclvcs with suicidal bchaviors. And
it is ohcn whilc in a mixcd statc that an individual is propcllcd into a varicty
of sclf- dcstructivc bchaviors that arc not immcdiatcly lifc- thrcatcning. Tcy
may cut or burn thcmsclvcs. Paticnts havc told mc that dcspcratc bchaviors
likc thcsc hclp thcm shih a tcrriblc inncr pain and tcnsion to "thc outsidc
and that thc physical pain is somchow casicr to dcal with than thc painml
agitation of a mixcd statc.
Anothcr typc of mood "mixturc occurs whcn, rathcr than a truc mix-
turc of simultancous mania and dcprcssion, thcrc is rapid altcrnation bc-
twccn thc two statcs. Kracpclin dcscribcd "transition pcriods hom onc statc
to anothcr, which ohcn cxtcndcd] ovcr wccks,' during which his paticnts
sccmcd dcprcsscd onc momcnt and manic ncarly thc ncxt.
Manic paticnts may transitorily appcar not only sad and dcspairing,
but also guict and inhibitcd. A paticnt gocs to bcd moody and inhib-
itcd, suddcnly wakcs up with thc fccling as if a vcil had bccn drawn
away hom his brain, passcs thc day in manic dclight in work, and thc
ncxt morning, cxhaustcd and with a hcavy hcad, hc again hnds in him-
sclf thc wholc miscry of his statc. r thc hypo manic cxultant paticnt
guitc uncxpcctcdly makcs a scrious attcmpt at suicidc.''
Rcccntly thc tcrm u| |m-m|d cyc||nyhas bccn proposcd fr such altcrna-
tions in mood.
ow that you havc somc fmiliarity with thc symptoms of bipolar dis-
ordcr, I can talk about diagnosis. As I havc alrcady said, most pcoplc with
bipolar disordcr ncvcr dcvclop all thc possiblc symptoms of thc illncss. It is
thc prcscncc or abscncc of ccrtain symptoms as wcll as thc pattcrn of mood
symptoms that allows a diagnosis of a particular typc of bipolar disordcr.
And oncc a diagnosis has bccn madc, a trcatmcnt plan can bc dcvclopcd. In
thc ncxt chaptcr you'll scc how thc diagnostic proccss works.
iLVA1 i1 iLVA1 ALL1 M 2,
L M A 1 H 2
O I1dgOS1S O1 1O1d1 I1SO1UO1
fr bipolar disordcr, psychiatrists startcd to rcalizc that not all cascs of thc
disordcr wcrc thc samc. Ior somc paticnts, lithium was indccd a miraclc,
thcir symptoms wcrc complctcly controllcd by it, and thcir illncss sccmcd
simply to cnd. 5ut othcr paticnts-ohcn thosc with lcss scvcrc symptoms or
morc hcgucnt cpisodcs of abnormal mood-didn't rcspond as wcll to thc
mcdication. Oid thcsc pcoplc havc bipolar disordcr, or somcthing clsc Pa-
ticnts who had bccn thought to havc "cyclothymic pcrsonality disordcr -a
diagnostic catcgory i n an ol d cdition of thc diagnostic manual of thc Amcr-
ican Psychiatric Association-also saw thcir troublcsomc and unprcdictablc
mood variations stop whcn thcy took lithium, did thcsc pcoplc havc bipolar
disordcr, and not a pcrsonality problcm ahcr all Was this a mildcr frm of
"manic- dcprcssivc illncss, or a dihcrcnt disordcr altogcthcr Oid it mattcr
What dihcrcncc docs diagnosis makc, anyway
Oiagnostic classihcation has two purposcs in mcdicinc. to makc prcdic-
tions about thc coursc of an illncss, and to aid thc clinician in sclccting thc
trcatmcnt most likcly to bc chcctivc. In thc practicc of psychiatry, sincc thc
physical basis fr most psychiatric illncsscs has yct to bc discovcrcd, classi-
hcation systcms arc largcly dcrivcd hom studying groups of paticnts with
dihcrcnt combinations of symptoms and sccing how thc dihcrcnt groups
vary in thc coursc of thcir illncss or in thcir rcsponsc to mcdications.
As morc and morc mcdications havc bccomc availablc to trcat mood
disordcrs, thc classihcation systcm fr bipolar mood disordcrs has contin-
ucd to cvolvc. In this chaptcr, various subtypcs of bipolar disordcr arc dc-
scribcd. Thcsc arc thc subtypcs that currcntly sccm to makc scnsc to clini-
cians bccausc thcy scrvc onc of thc two purposcs of diagnosis. thcy allow
fr a bcttcr prcdiction of thc coursc of thc illncss, and thcy allow fr a morc
rapid sclcction of chcctivc thcrapy-saving thc paticnt timc that would bc
wastcd on trying an inchcctivc mcdication.
Psychatrc agnoss
At lcast oncc a month, it sccms, I scc a paticnt who asks to bc "tcstcd fr
bipolar disordcr' It's not an unrcasonablc rcgucst. Lnfrtunatcly, it's not a
rcgucst that can bc satishcd-not just yct. Thcrc's no blood tcst or x- ray or
biopsy that can diagnosc bipolar disordcr [and, fr that mattcr, thcrc is nonc
that can bc uscd to conhrm thc diagnosis of most of thc problcms psychia-
trists trcat) .
Thc rcason fr this sorry statc of ahairs i s that thc biological and chcmical
basis of bipolar disordcr rcmains a ncarly complctc mystcry, no onc knows
what to tcst fr. Ocspitc litcrally hundrcds of ycars of cxamining thc bodily
fluids and brain tissucs of individuals with mood disordcrs-hrst with thc
nakcd cyc, thcn with microscopcs, latcr with x- rays and scanning dcviccs,
and morc rcccntly with incrcdibly sophisticatcd biochcmical probcs-no
onc has bccn ablc to hnd in paticnts with this illncss any abnormalitics that
can bc accuratcly and rcliably mcasurcd as an aid in diagnosing thc disor-
dcr. Although work in thc gcnctics of bipolar disordcr holds thc promisc
that gcnctic markcrs fr thc illncss may bc discovcrcd i n thc not-too- distant
mturc-suggcsting that a blood tcst might bc possiblc that will idcnti at
lcast somc cascs of thc illncss-and although somc individuals with bipolar
disordcr havc bccn idcntihcd as having subtlc brain-scan abnormalitics [scc
"Picturing 5ipolar Oisordcr in thc 5rain in chaptcr I8) , again suggcsting a
possiblc diagnostic tool, thc clinical applications of thcsc hndings arc still in
thc mturc. Modcrn psychiatrists arc lch with thc samc diagnostic tools that
Lmil Kracpclin and othcr ninctccnth- ccntury psychiatrists had. thcir cycs
and cars.
Wc psychiatrists listcn to what thc paticnt and hcr fmily mcmbcrs say
whcn thcy dcscribc symptoms-thcir onsct, coursc, fluctuation, and impact
upon thc paticnt. Whcthcr othcr mcmbcrs of thc fmily suhcr hom a mood
disordcr i s an important piccc of infrmation. Wc obscrvc thc paticnt fr
thc signs of bipolar disordcr dcscribcd i n chaptcr 1 by pcrfrming a mcn|a|
s|a|uscxam|na||cn,thc psychiatrist's cguivalcnt of thc physical cxamination.
This cxamination consists of obscrving spccch pattcrns and bchavior, asking
gucstions about mood and thinking proccsscs, and cvaluating othcr aspccts
of mcntal mnctioning such as conccntration and mcmory. Ahcr this proccss
H 11LiLS1S L1 1PL1V 11SLV1V M 2
of history-taking and cxamination, a picturc cmcrgcs of thc pcrson and of
hcr symptoms, and thc coursc of hcr illncss bccomcs clcar. A particular di-
agnostic catcgory that sccms to bc a good ht with thc clinical infrmation
is idcntihcd. ncc thc diagnostic catcgory of thc illncss is dctcrmincd, wc
can makc prcdictions about thc mturc coursc of thc symptoms and, pcrhaps
morc important, can sclcct a trcatmcnt that has a good chancc of rclicving
thcm. In thc scctions that fllow, you can lcarn about thc dihcrcnt frms of
bipolar disordcr thc samc way young physicians training to bc psychiatrists
do. by hcaring hom paticnts.
BpoIar I

It had bccn scvcral ycars sincc I had sccn Richard in thc mood- disor-
dcrs clinic. Hc lookcd grcat. Although hc was only in his latc thirtics,
somc silvcr toncs in his hair madc him look oldcr and guitc distin-
guishcd. I rcmcmbcrcd that hc had always drcsscd wcll, but today, in
an obviously hncly tailorcd suit, a crisp whitc shirt, and a bcautiful silk
tic, hc lookcd-wcll, likc a million. I kncw that this could bc a vcry
good sign-or a vcry bad sign.
"That's a handsomc suit you'vc got on, Richard. Is i t ncw I askcd.
"I got it about a month ago,' hc said proudly, "in London. A tcr-
rihc shop on Savilc Row, thc samc onc Princc Charlcs gocs to' Hc
smilcd a littlc mischicvously. "And I know what you'rc thinking. no,
I wasn't manic whcn I bought it|
Rich ccrtainly kncw what mania was, as did scvcral mcmbcrs of
his fmily. His wcalthy parcnts had takcn control of his hnancial af-
firs in a lcgal- guardianship procccding, fr ycars hc hadn't cvcn bccn
ablc to writc a chcck at thc supcrmarkct. Rich hrst dcvclopcd manic
symptoms during law school, hc madc down paymcnts on not just onc
Porschc but thrcc bcfrc a chcck bounccd. Hc angrily stormcd into thc
bank's branch omcc to protcst, crcatcd guitc a sccnc, and cndcd up in
j ail, whcrc an astutc nursc frtunatcly arrangcd an immcdiatc psychi-
atric cvaluation. Richard was admittcd to a local psychiatric hospital
and had takcn his hrst dosc of lithium bcfrc his parcnts cvcn kncw
what had happcncd.
Hc stoppcd taking his lithium within a month ahcr lcaving thc
hospital and startcd having manic symptoms almost immcdiatcly. This
timc his manic cnthusiasm turncd to travcl rathcr than cars, and hc
uscd a crcdit card to buy an airlinc tickct to Iiji. Hc madc it as far as
Los Angclcs bcfrc his mania turncd dysphoric and irritablc again. Hc
startcd yclling at and shoving a sccurity guard who wantcd to cxaminc
his luggagc and wound up in j ail again-this timc with fcdcral chargcs.
Ahcr a talk with a good lawycr, anothcr hospitalization, morc lithium,
a lcavc hom law school, and a movc back homc, hc camc fr trcatmcnt
at thc univcrsity outpaticnt clinic whcrc I was training.
Richard's fthcr also suhcrcd hom bipolar disordcr and kncw,
hom his own turbulcnt cxpcricnccs with thc illncss, just how to handlc
thc situation. A pair of scissors to thc crcdit cards, a powcr of attorncy,
and a trip with Richard to thc psychiatrist's appointmcnts madc thc
dihcrcncc-as did thc fct that Richard was an intclligcnt fcllow who
[cvcntually) lcarncd hom cxpcricncc as wcll. Morcovcr, hc lcarncd
hom his fthcr that a patcrnal unclc who had bccn killcd in a car
accidcnt whcn Rich was a child had also actually probably dicd hom
thc discasc, thc singlc- passcngcr accidcnt had most likcly bccn a sui-
cidc. Rich madc thc dccision to takc control of thc illncss rathcr than
lct it control him. And as with most things, oncc hc madc thc dccision,
hc stuck to it. Rich applicd himsclf to staying wcll with cncrgy and
Thcrc was a timc ahcr hc brokc up with a girlhicnd whcn scvcrc
dcprcssivc symptoms almost ncccssitatcd anothcr hospitalization fr
Rich, hc spcnt furtccn to sixtccn hours in bcd cvcry day fr ncarly
thrcc wccks and put on almost hhy pounds. Iortunatcly, fmily sup-
port, an cxccllcnt clinical psychologist who saw him fr thcrapy, and a
highcr lithium dosc fr scvcral months got him through. Ahcr about
a ycar of maintaining a stablc mood, hc got into a local law school to
hnish his studics and cvcntually graduatcd at thc top of his class. Hc
took a j ob in cw York but now had rcturncd homc. "I couldn't pass
up thc opportunity to opcn my hrm's ncw branch omcc in my homc-
town, could I hc bcamcd.
Rich brought mc up to datc. A littlc hypomania had occasionally
cmcrgcd during thc summcrs whilc hc was working in cw York,
cspccially if hc was working too hard and didn't watch his slccp habits.
5ut Rich had obviously rcmaincd scrious about his mcntal hcalth, hc
monitorcd his moods and saw his psychiatrist rcgularly. Most import-
ant, hc was making carccr dccisions that rcflcctcd his knowlcdgc of his
illncss. "I think thc pacc will bc slowcr hcrc than in cw York. I may
not bccomc a millionairc guitc as guickly,' hc said mischicvously, "but
thcrc will also bc lcss risk of gctting sick, blowing it all, and having to
start ovcr again. So . . . I had my last lithium lcvcl donc thrcc months
ago, and it was o. 8. Whcn do you want mc to gct anothcr
It lookcd as if thc suit had bccn a vcry yccdsign.

H 11LiLS1S L1 1PL1V 11SLV1V M j1
M80| 8
MyD080| 8
ND|08l 0DD0
M|l0 0|SS| D0
V| 0|SS| D0
Iiouer z-I Mood changcs in bipolar I.
5ipolar I is thc dcsignation fr thc classic varicty of bipolar disordcr,
charactcrizcd by mll-blown manic attacks and dccp, paralyzing dcprcs-
sions. A schcmatic rcprcscntation of thc moods of bipolar I appcars in hgurc
z-I. Tc pattcrn of abnormal mood cpisodcs sccms to vary widcly, and thc
rhythm of thc illncss is almost as individual as thc paticnt who has it. Symp-
toms of bipolar I usually bcgin in thc latc tccns or carly twcntics [hgurc z-z),
although onsct at latcr agcs i s not uncommon. '
5ipolar I i s what physicians rcfcr to as a rclapsing and rcmitting illncss,
during thc coursc of thc illncss, its symptoms comc and go. Tis fcaturc of
bipolar I-it is actually a fcaturc of a||mood disordcrs-makcs it dimcult to
diagnosc, dimcult to trcat, and hcndishly dimcult to study. Tis dcscrvcs a
closcr look.
Whcn wc think about illncsscs of thc body, wc usually think of discascs
that havc a bcginning, a middlc, and an cnd. Takc, fr cxamplc, pncumonia,
an infcction of thc lungs causcd by bactcria. Tc discasc bcgins whcn fcvcr,
cough, chcst pains, and brcathing problcms appcar. Tcsc symptoms build
and worscn ovcr a pcriod of hours or somctimcs days. 5cfrc thc antibiotic
cra, paticnts rcachcd what was callcd a cr|s|spoint, whcn thcir bodics' nat-
ural dcfcnscs had mountcd thcir bcst chort against thc bactcrial invadcrs,
and thc paticnt cithcr startcd gctting bcttcr or dicd. Lithcr thc paticnt killcd
oh thc bactcria or vicc vcrsa, but in any casc thc discasc proccss camc to an
cnd. [Iortunatcly wc can now administcr antibiotics that usually givc thc
paticnt's dcfcnscs thc crucial cdgc against a bactcrial invadcr. )
How about a discasc not causcd by a frcign invadcr likc bactcria but
instcad onc in which thc body sccms to turn on itsclf. a discasc likc canccr-
say, lcukcmia In this casc a whitc blood ccll in thc body dcvclops an abnor-
mality that causcs it to start rcproducing uncontrollably. Most of thc cclls in
thc body rcproducc hom timc to timc, rcplacing thosc that wcar out. It is
thought that most canccrs arc causcd by an crror during ccll duplication that
rcsults in an abnormality in thc control ccntcr of onc of thc ncw cclls. This
abnormality causcs thc ccll to start rcproducing continuously. Morc and
morc abnormal cclls arc produccd, and in thc casc of lcukcmia thcy hll thc
bloodstrcam and lymph nodcs such that thc normal cclls cannot do thcir job
propcrly, thc immunc systcm fils, and thc paticnt dics. Many typcs oflcukc-
mia arc now curablc. Thc curcs basically involvc using ingcnious mcthods to
cradicatc cvcry singlc canccr ccll, climinating thc abnormally rcproducing
cclls altogcthcr, whcn thc abnormality is climinatcd hom thc body, things
rcturn to normal. Again, thc illncss bcgins whcn somcthing gocs wrong in
thc body, and it cnds [is curcd) whcn thc abnormality is corrcctcd and clim-
inatcd. Thc illncss is hnishcd fr good.
5ipolar disordcr is vcry dihcrcnt hom thcsc discascs, bccausc it docs
not simply havc a bcginning, a middlc, and an cnd. r pcrhaps it is morc
! 00
unde| !0 ! 0- ! 9 20-29 30-39 40-49 50-59 0-9 /0and
O| der
Age OI Onset
licuar2-2 Agc of onsct of bipolar disordcr in I,o| paticnts. Thcsc data wcrc
compilcd hom tcn didcrcnt studics carricd out bctwccn Ipp and Ip8|. Noticc
that carly adulthood is thc pcak timc fr thc onsct of thc disordcr.
Scurce. Frcdcrck K. Goodwn and Kay KcdhcId [amson, Man|c-Deress|ve I||ness cw
York: Oxrd Lnvcrsty Ircss, o), jz. Copyrght o by Oxrd Lnvcrsty Ircss, !nc.
Lscd by pcrmsson oI Oxrd Lnvcrsty Ircss, !nc.
H 11LiLS1S L1 1PL1V 11SLV1V M jj
accuratc to say that thc illncss sccms to havc many bcginnings and cndings.
thc symptoms of bipolar disordcr can dcvclop in an individual, and thcn
w||bcu|any|rca|mcn|a|a||thc symptoms may go away fr ycars at a timc-
a pattcrn that is ncarly uniguc among thc discascs that amict humankind.
Sincc most pcoplc arc morc fmiliar with discascs that cnd whcn thcir
symptoms go away, it is ohcn vcry dimcult fr paticnts and thcir fmilics to
undcrstand that although thc symptoms of bipolar disordcr can go into rc-
m|ss|cnahcr trcatmcnt [or cvcn spontancously) , thcy almost incvitably will
comc back if trcatmcnt to prcvcnt thcir rcturn is not in placc. Thc hallmark
of bipolar illncss-cspccially bipolar I-is thc tcndcncy of thc illncss to rc-
|asc.o mattcr how wcll thc symptoms of any onc cpisodc arc trcatcd, thc
illncss docs not cnd but instcad sccms mcrcly to hibcrnatc-and sym|cms
ow, back to a dcscription of thc charactcristics of bipolar I. Iortu-
natcly, many cxccllcnt clinical studics about thc coursc of bipolar disordcr
wcrc donc in thc ycars bcfrc chcctivc trcatmcnts fr it wcrc availablc, thcsc
studics documcnt and illustratc thc pattcrn of bipolar- disordcr symptoms
that occurs if thc illncss is not trcatcd-what physicians call thc na|ura|b|s-
|cryof thc illncss. '
How many cpisodcs of illncss did paticnts havc in thc days bcfrc trcat-
mcnt was availablc How long did thcir cpisodcs last What was thc lcngth
of timc bctwccn cpisodcs
In a Iq2 study, thc rccords of sixty- six paticnts with "manic- dcprcssivc
psychosis wcrc studicd, somc of thcsc individuals had bccn fllowcd fr up
to twcnty- six ycars. Although a fcw paticnts sccmcd to havc had only onc
cpisodc of illncss in thc pcriod of study, about onc-third had two to thrcc
cpisodcs, about onc-third had fur to six cpisodcs, and about onc-third had
Tzeir2-I Numbcr of cpisodcs of illncss in sixty-six paticnts
wth bipolar disordcr
Num|cr c{ c/scdcs
Morc than ;
Pcrccn|ayc c{ a|/cn|s
Scurce Oata hom 1omas A. C. Kcnnc, "Irognoss n Manc-Ocprcssvc Isychoss, Amer|-
can )curna| c) Ps)ch|a| 8 (t|z). 8ot-t|.
Nc|e 1s study was donc bcrc any trcatmcnts wcrc avaIabIc r bpolar dsordcr.
morc than scvcn [tablc z- I ) . A fcw had twcnty or morc cpisodcs. ' Lnfr-
tunatcly, whcn a diagnosis of bipolar I is madc, thcrc is no way to know
whcthcr thc individual will havc anothcr two or thrcc cpisodcs during his
lifctimc or morc than twcnty.
How long did cpisodcs of mania or major dcprcssion last bcfrc chcc-
tivc trcatmcnts wcrc availablc In thc I(z study, thc avcragc duration was
about six and a half months. 5ut wc also know that dcprcssions and manias
wcrc somctimcs shortcr and somctimcs lastcd much longcr. Kracpclin, writ-
ing at a timc whcn thcrc wcrc csscntially no chcctivc trcatmcnts, notcd.
Thc duration of individual attacks is cxtrcmcly varicd. Thcrc arc somc
which last only cight to furtccn days, indccd wc somctimcs scc that
statcs of moodincss or cxcitcmcnt . . . do not continuc in thcsc paticnts
longcr than onc or two days or cvcn only a fcw hours. Ior thc most
part, howcvcr, a simplc attack usually lasts six to cight months. n thc
othcr hand, thc cascs arc not at all rarc, in which an attack continucs
fr two, thrcc or fur ycars, and a doublc attack can] doublc that timc.
I havc sccn manias, which cvcn ahcr scvcn ycars, indccd ahcr morc
than tcn ycars, rccovcrcd, and a statc of dcprcssion which ahcr fur-
tccn ycars rccovcrcd. '
Modcrn psychiatrists no longcr scc paticnts who arc manic fr ycars at a
timc. Lhcctivc modcrn trcatmcnts bring thcsc cpisodcs to a closc, and thc
paticnt is usually bcttcr in a fcw days-wccks at thc most. Modcrn psychia-
trists do, howcvcr, scc paticnts who sccm to bccomc manic again and again,
month ahcr month, ycar ahcr ycar-ohcn cvcry timc thcy stop taking mcdi-
cation. Oo thcsc paticnts havc many cpisodcs, or do thcy havc many rclapscs
of a singlc cpisodc of scvcral ycars' duration I tcnd to think it's thc lattcr, but
thc rhythm of thc illncss makcs rcscarch vcry dimcult.
How about thc timc bctwccn attacks Ior many pcrsons with bipolar
disordcr, modcrn trcatmcnts arc guitc chcctivc at kccping thc cpisodcs hom
rccurring. 5ut how long did rcmissions last in thc days bcfrc thcsc trcat-
mcnts wcrc availablc Kracpclin notcd that thc timc bctwccn cpisodcs could
bc ycars, cvcn dccadcs. Among ;o "intcrvals that hc studicd in his paticnts,
Kracpclin fund onc casc in which thcrc wcrc frty- fur ycars bctwccn onc
cpisodc of illncss and thc ncxt. ` Howcvcr, subscgucnt studics havc shown
that, if untrcatcd, cpisodcs of bipolar disordcr ohcn occur morc and morc
hcgucntly in individual paticnts [hgurc z- ) . Thc illncss sccms to accclcratc
if untrcatcd, and in thc days bcfrc trcatmcnt was availablc, mood cpisodcs
tcndcd to rccur morc and morc hcgucntly as paticnts agcd. This accclcration
has profund implications fr trcatmcnt and prognosis, as wc shall scc in
chaptcr zo.
Anothcr hnding in thcsc oldcr studics is that somc paticnts tcnd to
H 11LiLS1S L1 1PL1V 11SLV1V M jj
"switch`' hom a dcprcssion to a manic cpisodc with no intcrval of normal
mood. In a I6 study, thc coursc of onc hundrcd manic cpisodcs was dc-
scribcd. " Many individuals had a pcriod of dcprcssion lasting scvcral wccks
or months and thcn switchcd into a manic cpisodc, again of scvcral months'
duration. In a fcw of thcsc paticnts, thcrc fllowcd anothcr switch and a third
phasc of thc cpisodc sct in. a long pcriod of dcprcssion. In this study, about
half of thc paticnts' manic cpisodcs showcd at lcast onc switch-a dcprcs-
sion cithcr bcfrc or ahcr a manic cpisodc. Scvcral studics suggcst that pa-
ticnts who "switch`' hom dcprcssion to mania havc a morc dimcult- to- trcat
frm of illncss than thosc who switch hom mania to dcprcssion.
5ipolar I is thc classic manic- dcprcssivc illncss, with mlly dcvclopcd
manic cpisodcs and cpisodcs of scvcrc dcprcssion, and it is also charactcr-
izcd by long pcriods of "hibcrnation in which thc symptoms tcmporarily
40 -

30 -

`g 20
2 3 4
Lpi sOdeNumOer
5 7
licuar2-j Accclcration of illncss in onc hundrcd paticnts. Tis graph shows
that thc cyclc lcngth of cpisodcs of bipolar disordcr [thc timc hom thc onsct of
onc cpisodc to thc onsct of thc ncxt) bccomcs shortcr and shortcr in paticnts
whosc symptoms arc not wcll controllcd and who continuc to havc cpisodcs of
thc illncss.
Scurce Oata hom I. I. Koy-burnc, K. M. Iost, 1. W. Lhdc, 1. Iorcu, and O. Oavs, "1c Lon-
gtudnal Coursc oI Kccurrcnt Ahcctvc !llncss. Lh Chart Oata hom Iatcnts at thc !MI,
Ac|a Ps)ch|a|r|ca Scand|nav|a ;, suppI. j; 8): -jq.
Tzeirz-z Icaturcs of bipolar I
Fully developed manic episodes
Fully developed depressive episodes
O|bcr {ca|urcs
Untreated episodes average six months
Hallucinations and delusions hequently seen
Tree-phased episodes depression, mania, depression)
Relapses more hequent as patient ages
disappcar [ tablc z- z) . Thc numbcr of cpisodcs varics cnormously, but pa-
ticnts who havc only onc or two cpisodcs sccm to bc thc cxccption rathcr
than thc rulc. 5cfrc chcctivc trcatmcnts bccamc availablc, thc avcragc lcngth
of cach cpisodc if untrcatcd was about six months-but cpisodcs that lastcd
ycars wcrc not at all uncommon.
BpoIar II

Robcrt was a thirty-ninc-ycar- old accountant who had bccn sccing a
psychologist fr trcatmcnt of dcprcssion fr about thrcc months. 5oth
hc and his thcrapist wcrc hustratcd bccausc, dcspitc thc bcst chorts of
both, Robcrt's dcprcssion sccmcd to bc gctting worsc.
"I can usually pull mysclf out of thcsc things-or at lcast I can
usually slog through thcm until thcy hnish,' hc told mc at our hrst
appointmcnt. Right away, his dcscription of his dcprcssions as "thcsc
things madc mc fccl prctty ccrtain that this fcllow had a mood disor-
dcr. Robcrt's moods had an alicn, cxtcrnal guality to him, thcy camc
upon him likc a fg bank rolling in, lastcd fr a fcw wccks, and thcn
slowly dissipatcd. Whcrc thcy camc hom and whcrc thcy wcnt was a
complctc mystcry to Robcrt. Hc would slccp away thc wcckcnds, put
on wcight, fll bchind in his work. " This has bccn happcning to mc
sincc collcgc,' hc said, "and I rcally want it to stop.' In fct, this was
not thc worst his dcprcssions had cvcr gottcn. Shortly ahcr graduation,
Robcrt had had such a scvcrc dcprcssion that hc had spcnt most of thc
summcr at homc in his room. At onc point hc scriously contcmplatcd
suicidc. Thc only rcason hc didn`t gct into trcatmcnt thcn was bccausc
hc fclt hc was no worsc oh than his mothcr.
Robcrt's mothcr was a closct alcoholic. " Thcrc was always onc of
H 11LiLS1S L1 1PL1V 11SLV1V M j,
thosc hugc bottlcs of winc in thc rchigcrator,' hc told mc. "It always
sccmcd cithcr mll or half mll, and whcn I was in high school I rcal-
izcd that this was bccausc shc drank about a half a gallon cvcry day'
Robcrt's mothcr had ncvcr had any trcatmcnt fr cithcr hcr drinking
problcm or dcprcssion, but his dcscription of thc long "naps shc
took most ahcrnoons and thc "sick hcadachcs that put hcr in bcd fr
wccks soundcd likc morc than alcoholism-morc likc a smoldcring
dcprcssion complicatcd by alcohol addiction. Anothcr rcd flag fr a
mood- disordcr diagnosis. a positivc fmily history.
Robcrt had always blamcd his mclancholic moods on his child-
hood. Thc mcmorics of his shamc and worry about his mothcr sccpcd
back into his consciousncss during thcsc timcs, as did guilty fcclings
that hc had put hundrcds of milcs bctwccn himsclf and his mothcr
now, hadn`t sccn hcr in ovcr two ycars, and could bring himsclf to call
hcr only on holidays. Hcrc was morc cvidcncc pointing to a mood
disordcr . guilty fcclings and painml prcoccupations with thc past that
sccmcd rcally to bothcr him only whcn his mood changcd. Although
I wasn`t guitc hnishcd taking his history, I was alrcady thinking about
which antidcprcssant to rccommcnd to him, whcn Robcrt gavc mc
anothcr piccc of infrmation that changcd cvcrything.
"I cvcn fccl likc my thinking is slowcr than usual. I'll ncvcr gct
through tax scason unlcss I do somcthing to gct somc hclp-or unlcss
onc of my highs kicks in'
"nc of your . . .
"I call i t a high. 5ut it's not likc I'm manic- dcprcssivc or anything.
It's just that somctimcs whcn things gct back to normal I'm so rclicvcd
and happy that-oh, I don`t know, it just fccls so good not to bc dc-
"Oo you hnd that you'rc cspccially productivc during thcsc
timcs I askcd.
"h, dchnitcly. nc ycar I camc out of a dcprcssion just in timc fr
tax scason. I didn't fccl ovcrwhclmcd likc I usually do. It was spring,
and I wasn't dcprcsscd fr a changc, and I had just mct thc girl I was
going to marry-in fct wc got marricd that summcr, and so of coursc
things scttlcd back down. 5ut that was a grcat ycar'
"Oo othcr pcoplc noticc
"Lm, ycs, cspccially at thc omcc. ` Slow down, Rob ` Takc it casy,
Rob Somctimcs I gct irritatcd by that'
I had a fcw morc gucstions to ask, but I was bcginning to think
about how to tcll this fcllow that hc probably had "manic- dcprcssion
ahcr all.

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licuar2-q Mood changcs in bipolar II
5ipolar II is charactcrizcd by mlly dcvclopcd dcprcssivc cpisodcs and cpi-
sodcs of bycman|a. A schcmatic rcprcscntation of thc moods of bipolar II
appcars in hgurc 2-q.
Whcn lithium bccamc availablc i n thc Lnitcd Statcs i n thc I;os and
rcscarchcrs wcrc trying to hnd bcttcr diagnostic critcria fr bipolar disor-
dcr, scvcral of thcm noticcd that thcrc was a largc group of paticnts who
didn`t havc a history of mlly dcvclopcd manic cpisodcs but who sccmcd to
bc bipolar noncthclcss. Tcy had scvcrc dcprcssions, but thcir "highs ncvcr
dcvclopcd into mania. Wcrc thcsc paticnts "manic- dcprcssivcs who wcrc
still carly in thc coursc of thcir illncss and simply hadn't had timc to havc
a mlly dcvclopcd manic cpisodc Scvcral studics attcmpting to answcr this
gucstion concludcd that thcsc paticnts did nc|usually go on to mlly dcvcl-
opcd mania. In onc study, fcwcr than pcrccnt of thc paticnts with rccurrcnt
dcprcssions and hypomania cvcr bccamc manic.
It is firly clcar hom thc rcscarch litcraturc that bipolar II is not mcrcly a
prcludc to "mll-blown manic- dcprcssivc illncss-that is, bipolar II paticnts
arc not in thc carly stagcs of bipolar I.
5ipolar II i s somctimcs crroncously charactcrizcd as a mildcr frm of
bipolar I. 5ut although paticnts with bipolar II do not dcvclop thc most sc-
vcrc symptoms of mll-blown mania, thcy tcnd to bc symptomatic morc of
thc timc, and thcir long pcriods of dcprcssion can bc cvcn morc dcbilitating
than thc dramatic, but shortcr-livcd, cpisodcs of bipolar I illncss.
5ipolar II disordcr is morc common, morc gcnctically complcx, and
morc challcnging to trcat than bipolar I. Ocpcnding on thc critcria uscd
to makc thc diagnosis, this frm of thc illncss has bccn cstimatcd to amict
about pcrccnt of thc gcncral population, mcaning that it may bc hvc timcs
morc common than bipolar I disordcr. ' Scvcral studics show that bipolar
H 11LiLS1S L1 1PL1V 11SLV1V M j
Tzeirz- Icaturcs of bipolar II
Fully developed depressive episodes
Hypomanic episodes
O|bcr {ca|urcs
Increased sleep and appetite during depressions
Depressions sometimes more chronic
Bipolar II history in family members
Later age at nrst hospitalization
Fewer hospitalizations
Possible increased risk fr alcoholism
II paticnts ohcn havc rclativcs who also suhcr hom a bipolar mood dis-
ordcr charactcrizcd by major dcprcssions and hypomanias, but thcy also
ohcn havc fmily mcmbcrs who havc bipolar I as wcll as unipolar dcprcssivc
disordcrs [that is, symptoms of dcprcssion but without cithcr mania or hy-
pomania) . '" In onc study of bipolar I and II voluntccrs, z6 pcrccnt of bipolar
II paticnts had a rclativc with somc kind of psychiatric illncss [cspccially
anxicty disordcrs and addiction), as comparcd to only I pcrccnt of bipo-
lar I paticnts. ' ' This gcnctic infrmation i s not of acadcmic intcrcst alonc.
As you will scc in a latcr chaptcr, wc can think of thc brain`s mood-control
systcm as a vcry complcx and hncly tuncd clock with a myriad of intricatc
moving parts, cach of which is fbricatcd using instructions codcd in our
OA [gcncs) . Wc can think of bipolar I as bcing causcd by dcfccts in a fcw
of thc biggcr parts, causcd by glitchcs in thc instructions [thc gcncs) , thcn
bipolar II is causcd by many morc dcfccts in many morc of thc smallcr parts.
5ccausc morc parts nccd hxing, thcrc arc morc complicatcd symptoms and
a nccd fr morc complicatcd trcatmcnts.
And indccd, studics indicatc that thc symptoms and coursc of illncss of
bipolar II arc dihcrcnt hom thosc of bipolar I [tablc z- ) . 5ipolar II paticnts
havc morc problcms with dcprcssion-in fct, thc dcprcssion is somctimcs
so promincnt that many rcccivc a diagnosis of dcprcssivc disordcr and don`t
gct trcatmcnt fr bipolar disordcr at all. In a study hom thc ational Insti-
tutcs of Hcalth publishcd in I, paticnts diagnoscd with a dcprcssivc
disordcr wcrc fllowcd ovcr timc, somc fr up to clcvcn ycars. It was rcportcd
that almost pcrccnt of thcm dcvclopcd symptoms of bipolar II. ' ' Thc hrst
hypomanic cpisodc could usually bc documcntcd within scvcral months of
thc onsct of scvcrc dcprcssion, but somctimcs it took up to ninc ycars fr thc
corrcct diagnosis to bccomc clcar. Somc of thcsc "dcprcssion paticnts
also dcvclopcd a manic cpisodc-that is, thcy turncd out to havc bipolar I-
but this was fr lcss common [only . pcrccnt) . Thc study also fund that
bipolar II paticnts had longcr dcprcssivc cpisodcs [yz. z wccks) than bipolar
I paticnts [z(. wccks) and that, if untrcatcd, thcir symptom-hcc intcrvals
wcrc shortcr. This mcans that thcy had symptoms ovcr longcr strctchcs of
timc, thcy had what doctors call a cbrcn|ccoursc of illncss.
Pcrsons with bipolar II arc morc likcly to havc a scasonal variation in
thcir symptoms [thcy tcnd to gct dcprcsscd in thc fll and wintcr and fccl
bcttcr-or cvcn dcvclop hypomania-in thc spring and summcr), and thcy
havc morc rapid cycling [scc bclow) . Whcrcas paticnts with bipolar I hc-
gucntly havc irritablc manic symptoms, thc hypomanic pcriods of bipolar
II paticnts arc charactcrizcd by an clatcd mood-irritability is lcss common.
With rcgard to dcprcssivc symptoms, psycho motor agitation, guilty fcclings,
and thoughts of suicidc wcrc morc hcgucntly obscrvcd in bipolar II 5ipolar
II paticnts also havc a highcr incidcncc of phobias and cating disordcrs. ' '
CycIothymc sordcr
Cyclothymic disordcr - |bym|a, hom thc Crcck word fr "mind,' is uscd
in psychiatry to rcfcr to mood) is charactcrizcd by hcgucnt short pcriods
[days to wccks) of dcprcssivc symptoms and of hypomania scparatcd by pc-
riods [which also tcnd to bc short, on thc ordcr of days to wccks) of firly
normal mood. 5y dchnition, thc paticnt docs not havc cithcr mlly dcvclopcd
major dcprcssivc cpisodcs or mlly dcvclopcd manic cpisodcs. A schcmatic
rcprcscntation of thc moods of cyclothymia appcars in hgurc z-y .
Lmil Kracpclin bclicvcd that thcrc wcrc "ccrtain tcmpcramcnts which
could] bc rcgardcd as rudimcnts of manic- dcprcssivc insanity that might
continuc "throughout thc wholc of lifc as pcculiar frms of psychic pcrson-
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licuarz-y Mood changcs in cyclothymia.
H 11LiLS1S L1 1PL1V 11SLV1V M q1
ality without mrthcr dcvclopmcnt' Hc dcscribcd thc "cyclothymic tcmpcr-
amcnt as "charactcrizcd by hcgucnt, morc or lcss rcgular fluctuations of
thc psychic statc to thc manic or to thc dcprcssivc sidc''' Hc rcportcd that
j to q pcrccnt of his paticnts had thc cyclothymic tcmpcramcnt but spccu-
latcd that many morc pcrsons might havc similar illncsscs that "run thcir
coursc outsidc of institutions' Modcrn rcscarch on community populations
has provcd Kracpclin [as usual) guitc corrcct. Scvcral studics havc shown
that cyclothymic disordcr probably ahccts j to 6 pcrccnt of thc population. ' `
Clcarly, most of thcsc individuals arc ncithcr diagnoscd nor trcatcd fr thcsc
mood problcms [fcwcr than 6 pcrccnt of thc gcncral population cvcr rcccivc
trcatmcnt fr any psychiatric problcm) .
Kracpclin`s dcscriptions of thc symptoms of cyclothymia arc livcly and
vivid. " Thcsc arc thc pcoplc who constantly oscillatc hithcr and thithcr bc-
twccn thc two oppositc polcs of mood, somctimcs `rcj oicing to thc skics,
somctimcs `sad as dcath Today livcly, sparkling, bcaming, mll of thc joy of
lifc, thc plcasurc of cntcrprisc, and thc prcssurc of activity, ahcr somc timc
thcy mcct us dcprcsscd, cncrvatcd, ill-humorcd, in nccd of rcst, and again a
fcw months latcr thcy display thc old hcshncss and clasticity' ' "
Ior many ycars Amcrican psychiatric classihcation systcms rcgardcd
cyclothymia as a pcrsonality problcm. Thc conccpt of "tcmpcramcnt,' which
can bc thought of as a pcrson`s usual manncr of thinking, bchaving, or rc-
acting, capturcs thc samc idca. Cyclothymia was thought to bc bcttcr un-
dcrstood as an cxprcssion of a pcrson`s pcrsonality than as an illncss causcd
by an abnormality of brain chcmistry. In carly cditions of thc D|aycs||c
andS|a||s||ca|Manua|of thc Amcrican Psychiatric Association [thc DSM),
thc disordcr was callcd cyc|c|bym|ccrscna|||yd|scrdcr. In I8o cyc|c|bym|c
d|scrdcrmovcd ovcr to thc mood- disordcr scction of thc manual-whcrc it
rcmains today.
Individuals with cyclothymic disordcr havc vcry hcgucnt ups and downs
Tnsir 2-q Icaturcs of cyclothymic disordcr
Frequent alternation between mild depression and mild hyomania
Short, irregular cycles days)
Only short periods of normal mood
O|bcr {ca|urcs
Patients o6en wake up with mood changes
Pattern appears in late teens, early twenties
Frequently mistaken fr problem with personality''
Sometimes develops into bipolar I or II
Tzeirz- Mood, thinking, and bchavor pattcrns in frty-six
cyclothymic paticnts
Irritable periods lasting a few days
Explosive, aggressive outbursts
Sha| self-esteem alternating between lack
of self-conndence and overconndence
Periods of mental conmsion alternating with
periods of sharpened, creative thinking
Ac|/v/|y and |cbav/cr
Increased sleep alternating with decreased need fr sleep
Unevenness in quantity and quality of work
Buyng sprees, extravagance, or nnancial disasters
Repeated shi6s in work, study, interest, or mture plans
Drug or alcohol abuse
Extroversion alternating with introversion
Unelained promiscuity or extramarital anairs
}oining new movement with enthusiasm, rapidly
changing to disillusionment
Pcrccn|ayc c{ a|/cn|s
Scurce Oata hom I. AkskaI, M. K. Khan, and A. Scott- Strauss, "Cyclothymc 1cmpcr-
amcntaI Osordcrs, Ps)ch|a|r|c C||n|cs c) Ncr|h Amer|ca z ;): z;-q, guotcd n Frcd-
crck K. Goodwn and Kay Kcdhcld [amson, Man|c-Deress|ve I||ness cw York. Oxrd
Lnvcrsty Ircss, o), q.
of mood, with only comparativcly fcw pcriods of "normal mood [tablc z-() .
As Kracpclin notcd, thcy sccm to "constantly oscillatc . . . bctwccn thc two
oppositc polcs of mood' [Tis almost constant instability pcrhaps cxplains
why psychiatrists thought of this as a "pcrsonality charactcristic fr so
long.) As might bc cxpcctcd, constant mood instability causcs instability in
many arcas of thc paticnt's lifc. In a I study of frty-six paticnts with cy-
clothymia, thc paticnts dcmonstratcd a wholc varicty of oscillations of cmo-
tions and bchavior-hom slccp pattcrns t o work habits t o group amliations
[tablc z- ) . '
Cyclothymic disordcr bcgins carly i n lifc-in thc latc tccns or carly twcn-
tics . ' Although many pcrsons with cyclothymic disordcr ncvcr dcvclop
morc scvcrc mood symptoms, a signihcant numbcr of thcm cvcntually cxpc-
ricncc a mlly dcvclopcd dcprcssion or manic cpisodc-that is, thcy dcvclop
bipolar disordcr. In onc study, about 6 pcrccnt of paticnts with cyclothymic
disordcr cvcntually had a manic cpisodc, putting thcm in thc bipolar I cat-
H 11LiLS1S L1 1PL1V 11SLV1V M qj
cgory, but a highcr numbcr [zy pcrccnt) dcvclopcd scvcrc dcprcssion-that
is, thcy turncd out to havc bipolar II. ' ' Howcvcr, pcrhaps half of paticnts
with thc cyclothymic pattcrn ncvcr dcvclop symptoms of mll-blown bipolar
disordcr-a hnding that makcs cyclothymic disordcr a truc diagnosis in its
own right.
Iamily- history studics indicatc somc rclationship bctwccn cyclothymia
and othcr bipolar disordcrs. Paticnts with cyclothymia ohcn havc rclativcs
with bipolar disordcr but rarcly havc rclativcs suhcring hom dcprcssions
only.'" Trcatmcnt cxpcricnccs sccm to conhrm this rclationship. thc mood
swings of cyclothymic disordcr ohcn rcspond to many of thc samc trcat-
mcnt approachcs as thc bipolar disordcrs. This hnding also conhrms that
cyclothymia is just as much a "chcmical problcm as thc othcr bipolar disor-
dcrs and shows that thinking of thc mood swings of cyclothymia as arising
hom pcrsonality problcms is not hclpml in making trcatmcnt dccisions.
BpoIar Spcctrum sordcrs
If you look at thc cnd of thc scction on bipolar disordcrs in thc hhh
cdition of thc D|ayncs||candS|a||s||ca|Manua|of thc Amcrican Psychiatric
Association, you will scc thc catcgory "bipolar disordcr not clscwhcrc clas-
sihcd [also, simply, "bipolar LC) . This odd catcgory cxists bccausc thc
dcvclopcrs of thc DSMrccognizcd that thcrc arc paticnts who sccm to havc
somc kind of bipolar disordcr but who don't mcct thc diagnostic critcria fr
bipolar I or II or cyclothymia .

Maria is a violinist in thc local symphony orchcstra. Shc is ncarly scv-
cnty but looks much youngcr. 5orn in what is now thc Czcch Rcpublic,
shc dcfcctcd to thc Lnitcd Statcs during a tour of a chambcr music
group in thc I8os. Maria fund hcrsclf in cw York with only a small
suitcasc of clothcs, hcr violin, and a charming Luropcan acccnt. Shc
crcdits thc lattcr two with hcr succcss in hnding good work with scv-
cral Amcrican orchcstras ovcr thc ycars.
"I must tcll you, Ooctor, that my son has startcd taking Lamictal,
just likc mc. His psychiatrist askcd him about my mcdications and put
my son on thc samc onc. It's so good to know hc's bcing trcatcd by a
psychiatrist as brilliant as you'
"ow, now, it was hardly brilliant of mc to-
"h, ycs, so humblc, so modcst you arc, just likc all gcniuscs'
This was a littlc gamc wc had playcd fr ycars, cvcr sincc I had put
hcr on a mood stabilizcr instcad of an antidcprcssant, thc ncw mcdi-
cation had controllcd hcr mood symptoms fr thc hrst timc in many
5ccausc shc had movcd to a ncw city cvcry hvc ycars or so, Maria
had sccn many dihcrcnt profcssionals fr hcr mood problcms-mostly
dcprcssion. Ior many of thosc ycars shc rcccivcd no trcatmcnt at all
but simply sloggcd through hcr pcriods of dcprcssion on hcr own.
Ouring thc I;os, a physician gavc hcr a prcscription fr thc tranguil-
izcr Valium, and although it didn`t trcat hcr dcprcssion vcry wcll, it
numbcd Maria`s fcclings cnough to kccp hcr going. Whcn shc movcd
to a ncw community, shc would bc ablc to gct morc prcscriptions fr
Valium by rcporting to hcr ncw doctor that it hclpcd hcr-which, ahcr
a fshion, it did. Ouring thc rcally bad timcs, Maria uscd alcohol to
augmcnt thc Valium's chcct. 5y thc timc shc was in hcr mid-frtics,
shc was wcll on hcr way to chcmical dcpcndcncy. nc tcrriblc ycar,
shc lost a j ob bccausc of missing scvcral rchcarsals and an important
conccrt whilc in a wcck-long alcohol- and Valium- induccd fg during
a pcriod of dcprcssion. Hcr husband lch hcr, and a month latcr shc got
word that hcr son, also a talcntcd musician, had droppcd out of thc
prcstigious conscrvatory hc had bccn attcnding and had disappcarcd.
Maria`s dcprcssion worscncd to thc point that shc took a ncarly
ftal ovcrdosc of Valium and alcohol. It was only bccausc thc man-
agcr of thc apartmcnt building whcrc shc was living happcncd to go
into hcr apartmcnt that particular day that shc cndcd up in a hospital
rathcr than in thc city morguc.
It was in thc psychiatric hospital that shc startcd taking an anti-
dcprcssant fr thc hrst timc, but thc Lcxapro that shc startcd taking
madc things worsc rathcr than bcttcr. Within thrcc days of starting
thc antidcprcssant, Maria startcd to havc hypomanic symptoms. Shc
fclt "wircd and agitatcd and couldn`t slccp. Shc startcd staying up latc
at night writing music, bccoming convinccd that shc had discovcrcd
ncw musical frms and ncw harmonics that would makc hcr fmous.
Hcr antidcprcssant mcdication was immcdiatcly stoppcd, and shc was
startcd on lamotriginc. Within days thc agitation had stoppcd. It took
much longcr fr hcr dcprcssion to lih complctcly, but it cvcntually did.
"You wcrc thc hrst doctor to undcrstand that I nccdcd a mood
stabilizcr fr dcprcssion, and that makcs you truly brilliant,' Maria
continucd, a raiscd cycbrow cmphasizing hcr slightly tcasing tonc.
I was thc lucky rccipicnt of a lot of gratitudc-gratitudc shc
somctimcs archly cxaggcratcd to kccp mc hom taking mysclf too
scriously-bccausc hcr moods wcrc stablc fr thc hrst timc in ycars on
a mood stabilizcr.
H 11LiLS1S L1 1PL1V 11SLV1V M qj
Starting a paticnt with a history of manic symptoms on an anti-
dcprcssant is somcthing psychiatric tcxtbooks warn against-but
Maria had had manic symptoms only oncc in hcr lifc, at agc sixty-six,
whilc taking an antidcprcssant. Oid this rcally makc hcr bipolar Shc
didn`t havc thc history of manic or cvcn hypomanic cpisodcs that
would makc hcr ht thc bipolar I or II diagnosis-yct shc clcarly had
somc typc of bipolar disordcr.

Psychiatrists havc long rccognizcd that thcrc arc many frms of bipolar
disordcr. Kracpclin notcd that "it is mndamcntally and practically impossi-
blc to kccp apart in any way thc various frms of bipolar disordcr and that
"cvcrywhcrc thcrc arc transitions''' Ior many ycars various clinicians havc
dcscribcd various typcs of "soh bipolar disordcr [tablc z- 6) , mostly in pa-
ticnts who had comc to thcm to bc trcatcd fr dcprcssion but whosc illncss
sccmcd rclatcd to bipolar disordcr. '' Tcrms likc scudc-un|c|ardcrcss|cn
and ||c|arIIIhavc bccn coincd to dcscribc various typcs of scvcrc dcprcs-
sions that havc somc fcaturcs of bipolar disordcr but do not fll into tradi-
tional catcgorics fr bipolar diagnoscs. hcn thcsc paticnts havc had a long
history of dcprcssivc-likc or manic- likc fcaturcs in thcir usual mood statc, or
"tcmpcramcnt,' which arc punctuatcd by thc morc scvcrc mood symptoms
that causc thcm to scck trcatmcnt.
As morc trcatmcnts fr bipolar disordcr bccomc availablc and as morc
rcscarch on thc mood disordcrs is donc, it is bccoming clcar that many pa-
ticnts who suhcr hom mostly dcprcssivc symptoms can bcncht hom trcat-
mcnt with mcdications fr bipolar disordcrs and may in fct havc a typc of
bipolar disordcr .

athan is thc hhy- hvc-ycar-old cxccutivc dircctor of a philanthropic
fundation. Hc dcscribcs himsclf as a "workaholic who fr ycars has
workcd sixtccn- to cightccn-hour days and slcpt only fur to six hours
a night. athan is fmous around town fr his buoyant optimism and
thc boundlcss cncrgy that hc says comcs hom "making a living giving
away othcr pcoplc's moncy,' but his stah knows that hc can bc impa-
ticnt and drivcn whcn dcadlincs approach or pcrsonncl problcms dis-
tract him hom dcvoting himsclf Ho pcrccnt to his mission. Hc camc to
mc fr trcatmcnt of miscrablc, irritablc, rcstlcss fcclings that had both-
crcd him fr scvcral ycars but had bccomc much worsc in thc prcvious
fcw months.
athan had had problcms with dcprcssion bcfrc but had ncvcr
rcccivcd any trcatmcnt with mcdication. Whcn hc was twcnty-hvc, hc
bccamc dcprcsscd ahcr a hicnd dicd in a hcak accidcnt whilc both
of thcm wcrc skiing. athan was a graduatc studcnt at thc timc and
ncarly droppcd out of school. Whcn hc was in his frtics, hc wcnt
through scvcral months of dcprcsscd mood, troublc conccntrating
on his work, and appctitc and wcight loss that hc and his psychiatrist
at thc timc labclcd a "midlifc crisis cxaccrbatcd by somc unplcasant
changcs in his job. Hc was in thcrapy fr about thrcc months, and hc
startcd fccling bcttcr ahcr hc cmbarkcd on thc job scarch that cvcntu-
ally lcd to his currcnt position with a prcstigious fundation.
"r maybc i t was thc othcr way around,' hc muscd.
"What do you mcan I askcd.
"Maybc I was ablc to look fr a ncw job bccausc I was fccling
"Oo you know if othcr pcoplc in your fmily havc had troublc
with dcprcssion
"My fthcr lch us whcn I was thrcc, and thcy say hc was in and out
of psychiatric hospitals his wholc lifc. 5oth his sistcrs wcrc alcoholics.
nc committcd suicidc'
athan was proud that dcspitc his childhood in a brokcn, impov-
crishcd homc, hc now hcadcd a fundation, signcd chccks fr millions
of dollars cvcry ycar, and was courtcd by prcsidcnts of hospitals and
univcrsitics cvcry day of thc wcck. "So why do I fccl this way hc
askcd. "It can't just bc strcss, I thrivc on strcss. Thcsc hopclcss fcclings
comc ovcr mc, thcsc `what's thc point' fcclings. Why now

athan suhcrs hom onc of thc "soh bipolar disordcrs that somc rc-
scarchcrs call ||c|arIII.

` Thcsc paticnts havc a basclinc mood that is a

bit "highcr than that of most pcoplc, a pcrsonality charactcristic that has
bccn callcd bycr|bym|c |cmcramcn| [tablc z-;) . Thcir usual cncrgy lcvcl
is high, thcy arc chccrml, talkativc, conhdcnt, and sociablc. Thc down sidc
of thcir pcrsonality stylc is that thcy tcnd to bccomc irritatcd casily and can
bc impulsivc, cvcn rccklcss at timcs. Thcy usually havc a fmily history of
bipolar disordcr and arc bothcrcd by rccurrcnt dcprcssions. Antidcprcssant
Tzeirz- 6 Indicators of "soh" bipolar disordcrs
Family history of bipolar disorder
History of mania or hypomania caused by treatment with antidepressants
History of mixed" mood states
Depressive, hyper,' or cycling temperament
Recurrent depressions
H 11LiLS1S L1 1PL1V 11SLV1V M q,
Tzeir2-/ Icaturcs of bipolar III
Family history of bipolar disorder
Hyperthymic temperament.
Habitual short sleeperless than six hours per day
Cheerml, optimistic personality style
Tendency to become irritable easily
Extroverted and sociable
Recurrent depressions
mcdication alonc can makc thcm morc irritablc and miscrablc or provokc a
manic or hypomanic cpisodc, but mood stabilizcrs can bc vcry hclpml.
Ior about a half ccntury, psychiatry dividcd mood disordcrs into cascs
of unipolar dcprcssion, an illncss charactcrizcd by only dcprcssivc symp-
toms, and bipolar disordcrs, in which paticnts suhcr dcprcssivc cpisodcs but
also manic, hypomanic, or mixcd statcs as wcll. 5ipolar spcctrum disordcrs
sccm to challcngc this way of thinking, many of thcsc paticnts havc an ill-
ncss that is dominatcd by dcprcssivc symptoms and shows only thc slight-
cst colorings of mania. Thcy may havc pcriods of clcvatcd mood that thcy
don't fccl arc particularly abnormal but that, whcn cxamincd morc closcly,
bcar thc hallmarks of hypomania. dccrcascd nccd fr slccp, incrcascd cn-
crgy, uncharactcristic ovcrconhdcncc, and loss of inhibitions. As mcntioncd
prcviously, pcriods of agitation and irritability that last only a fcw hours
may rcprcscnt mild mixcd statcs. I havc sccn many paticnts who havc bccn
unsucccssmlly trcatcd with onc antidcprcssant ahcr anothcr fr what thcy
havc bccn told is "unipolar dcprcssion' Ior many of thcsc paticnts, thcrc arc
bipolar fcaturcs in thcir illncss that havcn't bccn rccognizcd as such. Whcn
onc of thc mcdications morc typically uscd to trcat bipolar disordcr is prc-
scribcd, thcsc paticnts hcgucntly havc a signihcant improvcmcnt in thcir
dcprcssivc symptoms.
Somc paticnts with this kind of problcm bccomc upsct whcn I try to cx-
plain that a bcttcr trcatmcnt approach fr thcir dcprcssion might bc to trcat
it as a frm of bipolar disordcr , thcy worry that a diagnosis of bipolar dis-
ordcr mcans that thcy havc a morc scrious problcm than "just dcprcssion
or that thcy arc "rcally crazy' This rcaction ovcrlooks a couplc of fcts. hrst,
dcprcssion is always a scrious illncss, and sccond, many pcoplc with bipolar
disordcr ncvcr dcvclop mll-blown mania or psychotic symptoms [which is
what most pcoplc arc thinking of whcn thcy usc thc pcjorativc tcrm cracy). I
somctimcs usc thc tcrm ccm| |ca|cddcrcss|cnto talk about thcsc illncsscs.
Thc important point to rcmcmbcr is that, dcspitc what you might gathcr
hom rcading short ncwspapcr or magazinc articlcs about dcprcssion and bi-
polar disordcr, wc havcn't yct hgurcd out how to classify thcsc illncsscs. It is
bccoming clcar that many cascs that sccm to bc "just dcprcssion arc rclatcd
in somc way to bipolar disordcr. Many dcprcsscd paticnts who don't sccm to
havc classic "manic- dcprcssivc illncss will ncvcrthclcss bcncht hom mcdi-
cations uscd to trcat bipolar disordcr.
Rapd-CycIng BpoIar sordcr
Soon ahcr lithium bccamc availablc fr thc trcatmcnt of bipolar dis-
ordcr, psychiatrists noticcd that somc of thc sickcst bipolar paticnts didn't
sccm to dcrivc much bcncht hom it. Thcsc paticnts clcarly suhcrcd hom a
bipolar mood disordcr-thcy had scvcrc manias and dcprcssions-but thcy
wcrc sct apart hom othcr bipolar paticnts by thc hcgucncy of thcir cpisodcs .
Currcntly, rapid- cycling bipolar disordcr is diagnoscd if thc paticnt has fur
or morc cpisodcs [mania, hypomania, dcprcssion, or mixcd statc) in onc
Larly imprcssions and casc rcports sccmcd to indicatc that thcrc wcrc
fcaturcs othcr than hcgucncy of cpisodcs that sct rapid- cycling bipolar dis-
ordcr apart hom othcr bipolar disordcrs. It sccmcd to occur morc ohcn in
fcmalcs, usually bcgan with a dcprcssivc cpisodc, and was lcss rcsponsivc to
lithium thcrapy. Thcrc also sccmcd to bc somc indication that paticnts with
this pattcrn of illncss wcrc morc likcly to havc a history of thyroid gland
problcms and to havc bccn trcatcd with antidcprcssant mcdications. '' Thcrc
wcrc suggcstions hom somc rcscarchcrs that thcsc last two fctors-thyroid
discasc and trcatmcnt with antidcprcssants-might causc "normal bipolar
illncss to switch into rapid- cycling illncss. '`
f thcsc two fctors, thc most intcrcst has bccn fcuscd on thc possi-
bility that trcatmcnt with antidcprcssant mcdications can causc thc switch
hom "normal bipolar disordcr into a rapid- cycling frm. nc study cxam-
incd thc casc rccords of II8 paticnts who wcrc rapid cyccrs [had had fur or
morc cpisodcs of abnormal mood in onc ycar). '" Thc rcscarchcrs fund that
86 of thcsc paticnts sccmcd to havc had a changc in thc coursc of thcir ill-
ncss-that is, thcy had "switchcd into a rapid- cycling pattcrn. Thc authors
statcd that "thc majority of thcsc switchcd ahcr thcy wcrc trcatcd with an
antidcprcssant mcdication. Thc rolc of antidcprcssants in thc trcatmcnt of
bipolar disordcr-whcthcr pcrsons with bipolar disordcr should cvcn takc
antidcprcssants-rcmains a mattcr of dcbatc among cxpcrts, onc that I will
rcturn to in latcr chaptcrs.
A morc rcccnt study casts somc doubt on thc uscmlncss of talking about
rapid cycling as a spccihc typc of bipolar disordcr. ' In this study, I pa-
ticnts wcrc fllowcd ovcr a hvc-ycar pcriod, and any who mct thc critcria fr
rapid cycling [having had at lcast onc cpisodc of mania or hypomania and
thrcc additional cpisodcs of any typc during onc ycar) wcrc studicd closcly.
H 11LiLS1S L1 1PL1V 11SLV1V M q
Iorty- hvc paticnts turncd out to mcct thc rapid- cycling critcria, and thcir
fmily history, trcatmcnt coursc, and coursc of illncss wcrc comparcd with
thosc of thc "normal bipolar paticnts.
Thc picturc that cmcrgcd hom thcsc paticnts suggcstcd that rapid cy-
cling is a tcmporary phasc of bipolar illncss that somc paticnts arc pronc
to-not a particular typc of bipolar illncss. Thc rapid cycling stoppcd ahcr
a pcriod of scvcral months in frty- fur of thc frty- hvc paticnts who wcrc
studicd. Thcsc paticnts did not havc rapid cyccrs in thcir fmily, although
thcy did havc fmily mcmbcrs with "normal bipolar illncss. As timc wcnt
on, thcir rapid cycling gradually stoppcd. Thc only hnding hom thc carlicr
rcports that was conhrmcd was that morc womcn than mcn had rapid cy-
cling, ncarly thrcc- guartcrs of thc paticnts with rapid cycling wcrc womcn
[bipolar disordcr usually ahccts both scxcs about cgually) .
Somc bipolar paticnts [I8.y pcrccnt in this study) sccm to go through a
pcriod of rapid cycling fr somc months, during which thcir symptoms arc
morc dimcult to control-morc womcn than mcn [I discuss this in morc
dcpth in chaptcr I() . Although thcrc continucs to bc suspicion among many
clinicians that antidcprcssant mcdications can causc somc paticnts to start
rapid cycling, thc cxact causcs of rapid cycling rcmain a mystcry, as do, un-
frtunatcly, thc trcatmcnt stcps that will prcvcnt it.
Schzoathctvc sordcr
Somc paticnts havc an illncss with fcaturcs both of mood disordcrs and
of a vcry dihcrcnt psychiatric illncss. schizophrcnia. In addition to mood-
disordcr symptoms such as dcprcssion, hypomania, or mania, thcsc paticnts
havc thc hallucinations, dclusions, and othcr bizarrc mcntal cxpcricnccs
typical of schizophrcnia, thcy ohcn rcccivc thc diagnosis of schizoahcctivc
As wc havc sccn in chaptcr I, many paticnts with bipolar disordcr dc-
vclop dclusional bclicfs or hallucinations. 5ut in thc mood disordcrs, thcsc
symptoms can bc undcrstood as arising out of thc mood statc. Ior cxamplc,
in a scvcrc dcprcssion a paticnt might havc thc dclusional bclicf that shc
has a tcrriblc illncss likc AIOS or has lost all of hcr moncy, or that fmily
mcmbcrs arc bcing torturcd by kidnappcrs, bclicfs that arc, wcll, dcprcssing.
Manic paticnts may hcar thc singing of angcls or thc voicc of Cod-again,
hallucinations that can bc undcrstood as coming out of thc cxpansivc, gran-
diosc mood of mania. Oclusions [flsc bclicfs and idcas) and hallucinations
[flsc scnsory pcrccptions such as thc hcaring of voiccs) arc said to bc mccd
ccnyucn|whcn thcy can bc undcrstood as bcing part of thc abnormal mood.
Pcrsons with schizophrcnia havc bizarrc dclusions and hallucinations
too, but thcy don't usually sccm to bcar any rclation to a changc in mood.
Lxamplcs of schizophrcnic dclusions would bc thc bclicf that onc's ncxt-
door ncighbors arc pumping poisonous gas into onc's housc, or that onc's
rcal spousc and childrcn havc bccn rcplaccd by cxact rcplicas, or that thc
I5I has implantcd a transmittcr in onc's brain. Paticnts with schizophrc-
nia somctimcs bclicvc that othcr pcoplc arc rcading thcir minds or putting
into thcir hcads thoughts that arc not thcirs. Thcy might hcar thcir own
thoughts rcpcatcd to thcm aloud or hcar thc voiccs of unsccn commcntators
dcscribing thcir actions to othcr unsccn pcrsons. onc of thcsc symptoms
havc much rclationship to mood changcs. Morc importantly, pcrsons with
schizophrcnia do not cxpcricncc cpisodcs of sustaincd abnormal changcs in
mood. Whcn a pcrson has bizarrc dclusions or hallucinations likc thcsc or
has thcsc kinds of symptoms during timcs whcn thcy do not sccm to bc in
an cpisodc of abnormal mood, thc diagnosis of schizoahcctivc disordcr is
ohcn madc.
What is this disordcr, and whcrc docs it bclong in thc classihcation of
psychiatric discasc Thcsc arc gucstions that havc plagucd psychiatry fr
many ycars, wc still don't havc vcry good answcrs to thcm.
Is schizoahcctivc disordcr truly a scparatc disordcr, an illncss that sharcs
symptoms with mood disordcrs and schizophrcnia but is ncithcr If it is, it
has bccn vcry dimcult fr rcscarchcrs to agrcc on its dchning symptoms.
In an carlicr vcrsion of thc DSM, thc Amcrican Psychiatric Association's
classihcation manual fr mcntal illncsscs, thc diagnostic catcgory of schizo-
ahcctivc disordcr was includcd without anylisting of thc symptoms that dc-
hncd it.
I havc sccn paticnts who havc bccn diagnoscd with schizoahcctivc dis-
ordcr who sccm to mc instcad to havc a scvcrc casc of a mood disordcr
that has bccn dimcult to trcat. Paticnts can bc dclusional and havc hallu-
cinations whcn thcy arc vcry dcprcsscd or vcry manic, and if thcy arc in a
phasc of ultra-rapid cycling, thcsc symptoms can changc rapidly and do not
sccm to makc much scnsc in rclation to thcir moods. I havc sccn paticnts
diagnoscd with schizoahcctivc disordcr bccausc thcy havc promincnt para-
noid symptoms-that is, thcy bclicvc thcy arc bcing watchcd or fllowcd or
talkcd about. Although paranoid symptoms arc vcry common in somc typcs
of schizophrcnia and not as common in thc mood disordcrs, closc gucstion-
ing ohcn rcvcals thc mood componcnt in thcsc paticnts. In a book writtcn
during thc twcnticth ccntury callcd AM|nd7a|IcundI|scqClihord 5ccrs
dcscribcd his battlc with a mcntal illncss that was almost ccrtainly bipolar
disordcr. In onc sccnc hc dcscribcs a train ridc to thc psychiatric hospital.
As thc train passcd through thc stations along thc way, 5ccrs noticcd pco-
pl c standing on thc station platfrms rcading thc ncwspapcr. Hc bccamc
convinccd that thcy wcrc rcading about him. At hrst glancc, this symptom
docsn't sccm to havc any mood componcnt, and in fct it is a rathcr typical
H 11LiLS1S L1 1PL1V 11SLV1V M j1
symptom of schizophrcnia callcd an |dca c}rc}crcncc.Iortunatcly, howcvcr,
5ccrs dcscribcs this symptom in grcat dctail in his book and writcs that
hc thought thc pcoplc on thc train platfrms wcrc rcading about his long
history of mcntal illncss and about what a filurc hc had bccn. With this
addcd dctail-thc thcmcs of shamc and filurc in thc symptom-thc mood
componcnt bccomcs obvious and thc rcal diagnosis clcar. a mood disordcr.
Anothcr possiblc cxplanation fr thc mingling of symptoms of a mood
disordcr and of schizophrcnia i n onc paticnt i s that thc paticnt may suhcr
hom |c|b illncsscs. If onc considcrs that bipolar I ahccts about 1 pcrccnt
of thc population and that about 1 pcrccnt of thc population suhcrs hom
schizophrcnia, thcn obviously, if thcrc arc no othcr fctors opcrating to prc-
vcnt thc illncsscs hom occurring togcthcr, as many as O. OI pcrccnt of thc
population will suhcr hom both disordcrs-that is, onc in tcn thousand. If
onc adds in othcr mood disordcrs such as bipolar II, cyclothymia, and thc
"soh bipolar disordcrs, thc numbcrs of pcrsons with schizophrcnia who
also havc a mood disordcr will bc cvcn grcatcr. Trcatmcnt cxpcricncc would
sccm to support this idca. paticnts with a diagnosis of schizoahcctivc disor-
dcr sccm to bc most chcctivcly trcatcd with mcdications fr mood disordcrs
uscd in combination with mcdications fr schizophrcnia.
Indccd, somc paticnts' illncss dchnitcly sccms to combinc two disordcrs.
thcy havc thc kind of bizarrc dclusions common in schizophrcnia, which
sccm to havc nothing to do with an abnormal mood, but also havc clcar- cut
cpisodcs of dcprcssion and mania. This sccms to bc a rarc occurrcncc, but
it is important not to miss it. I havc occasionally sccn paticnts whosc psy-
chiatrist sccmcd rcluctant to makc thc diagnosis of schizoahcctivc disordcr,
pcrhaps not wanting to hightcn paticnts and fmilics with thc diagnosis of
an illncss that is usually morc impairing and dimcult to trcat than a bipolar
disordcr. This rcluctancc to diagnosc, howcvcr, can rcsult in not trcating thc
illncss aggrcssivcly cnough.
I oncc saw a paticnt whosc psychiatrist had rcfcrrcd him fr consul-
tation bccausc what had bccn diagnoscd as scvcrc bipolar dcprcssion with
psychotic symptoms had rcspondcd poorly to many dihcrcnt trcatmcnts fr
mood disordcrs. This paticnt was ccrtainly dcprcsscd, but his illncss-which
had rcguircd multiplc hospitalizations and had bccomc so disabling that hc
could no longcr work or cvcn livc in his own apartmcnt-had othcr fcaturcs
consistcnt with schizophrcnia. Ior this paticnt, trcatmcnt fr dcprcssion
was hclpml only up to a point. nly whcn hc was also prcscribcd clozapinc
[Clozaril), a mcdication usually rcscrvcd fr paticnts with scvcrc schizo-
phrcnia who havc filcd to bcncht hom othcr mcdications, did hc havc a
substantial rccovcry. Making a changc in diagnosis and rccommcnding a
vcry dihcrcnt trcatmcnt approach was upsctting fr this paticnt and his fm-
ily at hrst-fr just thc rcasons mcntioncd abovc. 5ut thc paticnt's parcnts
also admittcd that thcy had long suspcctcd that thcir son had "morc than
just bipolar disordcr,' and ahcr morc carcml cxplanation of my rcasoning
and mrthcr discussions with thc paticnt and his fmily, wc shihcd thc coursc
of thc trcatmcnt plan, ultimatcly with positivc rcsults. This is a lcsson in thc
importancc of making thc corrcct diagnosis in mood disordcrs.
A diagnosis of schizoahcctivc disordcr is in many ways morc scrious
than that of bipolar disordcr, sincc this illncss sharcs somc of thc fcaturcs
of schizophrcnia and somc of thc trcatmcnt challcngcs of that illncss . Oc-
lusions and hallucinations may rcspond incomplctcly to mcdication trcat-
mcnt, and morc scvcrc [and somctimcs progrcssivc) social and occupational
impairmcnt is not uncommon. Ior this vcry rcason, howcvcr, it is cvcn morc
important, if a diagnosis of schizoahcctivc disordcr is bcing considcrcd, to
bc cxtra carcml in rcvicwing thc symptoms and coursc of illncss and to usc
infrmation hom as many sourccs as possiblc.
H 11LiLS1S L1 1PL1V 11SLV1V M jj
L M A 1 H J
1O1d1 I1SO1UO1 dDU O -
fcssional and who rcad thcir diagnosis in thcir mcdical rccords or insurancc
statcmcnts ohcn havc gucstions about thc diagnostic catcgorics and tcrms
that arc uscd. Psychiatry is onc of thc fcw mcdical spccialtics that has a morc
or lcss omcial list of disordcrs and diagnoscs, and in this chaptcr wc'll takc
a closcr look at thc latcst vcrsion of this list, thc hhh cdition of thc D|ay-
ncs||c and S|a||s||ca|Manua| c}Mcn|a| D|scrdcrs [thc DSM-) , dcvclopcd
and publishcd by thc Amcrican Psychiatric Association. I' ll prcscnt a bricf
ovcrvicw of thc DSMand cxplain somc of thc diagnostic tcrminology fr
bipolar disordcr.
What Is thc OSM?
Thc roots of thc DSM-go back at lcast as fr as thc L. S. Ccnsus of I8(o,
which includcd thc catcgory of "idiocy/insanity in its systcm fr classifying
Amcrican citizcns. 5y I88o thcrc wcrc scvcn catcgorics into which pcrsons
with mcntal illncss could bc placcd. mania, mclancholia, monomania, pa-
rcsis, dcmcntia, dipsomania, and cpilcpsy. ' In II; thc Amcrican Mcdico-
Psychological Association-thc frcrunncr of thc Amcrican Psychiatric As-
sociation-dcvclopcd a statistical manual fr usc in mcntal hospitals that
includcd various catcgorics of diagnoscs. As timc wcnt on, othcr organiza-
tions intcrcstcd in thc statistics of mcntal illncss, such as thc Vctcrans Ad-
ministration and thc L. S. Army, dcvclopcd thcir own statistical manuals.
Ahcr World War II, thc World Hcalth rganization includcd a long scction
on mcntal disordcrs in thc sixth cdition of its In|crna||cna|C|ass]ca||cnc}
D|scascs[thc ICD6) .
In Iyz thc Amcrican Psychiatric Association publishcd thc D|aycs||c
andS|a||s||ca|Manua|:Mcn|a|D|scrdcrs [thc DSA ], which dihcrcd hom
prcvious statistical manuals in that it containcd a glossary dcscribing thc
symptoms of thc dihcrcnt disordcrs. Thus, in addition to an omcial list of
catcgorics of mcntal illncss, thc DSA Iprovidcd guidancc to thc clinician in
making psychiatric diagnoscs. 5y thc timc thc third cdition of thc manual
appcarcd in I8o, cach catcgory of psychiatric disordcrs had a list of d|ay-
ncs||ccr||cr|athesymptoms and othcr charactcristics of cach disordcr that
wcrc thought to dchnc it and sct it apart hom othcr psychiatric disordcrs.
Pcrhaps thc most valuablc usc of thc DSA is in rcscarch into thc causcs
and trcatmcnt of mcntal illncsscs. Lsc of thc DSA in rcscarch mcans that
whcn you hnd a study of somc particular psychiatric disordcr in a profcs-
sional j ournal and rcad that "thc paticnts mct thc DSA diagnostic critcria
fr that disordcr, you can bc surc that thc paticnts all had a ccrtain wcll-
dchncd collcction of symptoms and othcr charactcristics in common, that
thc rcscarchcrs wcrc not mixing, as it wcrc, psychiatric applcs and orangcs
in thcir study.
Thcrc arc problcms with thc DSA, howcvcr, and many cxpcrts havc bccn
cxtrcmcly critical of it. Thc DSA is csscntially a collcction of chccklists of
sym|cmsfr cach diagnostic catcgory and is not bascd on an undcrstand-
ing of thc causcsof cmotional problcms. This might sccm likc a guibbling
acadcmic gucstion at hrst, but it's not. As an cxamplc, a DSA-typc classihca-
tion systcm fr physical illncsscs might classify discascs bascd on thc scvcr-
ity and location of symptoms such as pain or fcvcr. A momcnt's thought rc-
vcals how usclcss such a systcm would bc. Paticnts coming to an cmcrgcncy
dcpartmcnt with symptoms of abdominal pain and a fcvcr might bc diag-
noscd with "Hot Painml 5clly Oisordcr.' 5ut sincc thcsc samc symptoms
can bc causcd by a myriad of dihcrcnt problcms, ranging hom appcndicitis
to gall stoncs to porphyria, to makc a diagnosis of "Hot Painml 5clly Oisor-
dcr is complctcly usclcss fr dcciding how to trcat thc paticnt. Switching
back to psychiatric diagnosis, good clinicians know that two paticnts might
havc ncarly idcntical symptoms of dcprcssion hom many dihcrcnt causcs
that rangc hom normal bcrcavcmcnt, to rcactions to long-tcrm dcprcssing
lifc circumstanccs such as povcrty or ongoing physical abusc, to biologically
and gcnctically causcd mood disordcrs. Cataloging thc sym|cmsis only a
hrst stcp in dcciding what to do fr thc paticnt. A list of symptoms docsn't
hclp dccidc whcthcr thc paticnt nccds gricf counscling, social work intcr-
vcntion to allcviatc conscgucnccs of povcrty, protcction hom an abusivc
partncr, or a prcscription fr an antidcprcssant.
1PL1V 11SLV1V i1 H DSM-j M jj
5ccausc thc DSM contains a list of psychiatric diagnoscs fllowcd by
succinct and clcarly writtcn "critcria' fr making thosc diagnoscs, it also
has thc unfrtunatc chcct of making psychiatric diagnosis look dcccptivcly
casy. It is tcmpting fr individuals who havc no psychiatric training to usc
this scrics of symptom chccklists to diagnosc mcntal illncss. Wcll, why not
Iirst of all, it is only with an cnormous amount of training and cxpc-
ricncc that onc can gain an apprcciation fr thc vcry widc rangc of ncrma|
cmotions and bchaviors and havc a scnsc of what flls outsidc this normal
rangc. Signihcant clinical cxpcricncc and judgmcnt arc nccdcd to dccidc
what constitutcs an "cxpansivc mood or an "incrcasc in cncrgy that is clin-
ically signihcant. I havc bccn callcd to scc "manic paticnts rcfcrrcd by thcir
counsclors or thcir fmily mcmbcrs and fund that thc paticnts, though a
bit morc intcnsc in manncr than most pcoplc, havc a mood statc pcrfcctly
within thc normal rangc. Thc DSM is mll of diagnostic critcria that usc
gualihcrs likc "clinically signihcant,' "markcd impairmcnt,' and "cxccssivc
involvcmcnt in . . . , all of which rcguirc judgmcnt bascd on cxpcricncc to
makc a dctcrmination. Lvcn somc counscling and thcrapy profcssionals, if
thcy havc not traincd in a sctting whcrc thcy havc had thc opportunity to
scc vcry sick paticnts, may not havc an apprcciation fr what constitutcs
"scvcrc -simply bccausc thcy havc ncvcr sccn and workcd with "scvcrcly
dcprcsscd or manic paticnts. onprofcssionals will, of coursc, usually havc
cvcn lcss cxpcricncc with thc rangc of normal and abnormal moods. With-
out thc cxpcricncc of sccing many paticnts with scvcrc mcntal illncsscs and
trcating thcm, it is impossiblc to accuratcly scparatc normal hom abnormal
mcntal cxpcricnccs or "clinically signihcant mood changcs hom thosc that
arc within thc rangc of thc normal. In psychiatry as pcrhaps in no othcr hcld,
thc dictum "A littlc lcarning is a dangcrous thing holds guitc truc.
Morcovcr, as wc shall scc in chaptcr I8, many mcd|ca| conditions can
mimic abnormal mood statcs, dozcns of pharmaccuticals can causc dcprcs-
sion or cuphoric statcs in somc pcrsons, and drugs of abusc can causc all
kinds of mood statcs and psychoscs in almost anyonc. Almost all thc DSM
diagnoscs contain "cxclusion critcria' fr mcdical conditions, such as "thc
symptoms arc not duc to a gcncral mcdical condition' A physician will prob-
ably noticc thc abnormalitics in thc fcial appcarancc of a paticnt with
Cravcs' discasc or Cushing's syndromc as soon as thc paticnt walks into thc
room, thc nonphysician probably has ncvcr hcard of thcsc illncsscs and
docsn't know that thcy can causc psychiatric symptoms practically idcntical
to thosc of a maj or dcprcssion cpisodc. Thc physician knows wcll thc typical
walk of thc paticnt with Parkinson's discasc and thc subtlc languagc prob-
lcms of thc paticnt who has had a silcnt strokc-both ncurological condi-
tions that can causc mood symptoms. bviously, only a clinician traincd in
thc diagnosis and trcatmcnt of physical illncss will bc ablc to pick up thcsc
sorts of problcms.
Iinally, just as thc rangc of normal cxpcricnccs and bchaviors is cnor-
mous, so is thc rangc [ and complcxity) of abnormal mcntal cxpcricnccs and
bchaviors, thcy cannot bc containcd in any onc book and ccrtainly cannot
all bc dcscribcd in a fcw dozcn diagnostic catcgorics. Alhcd Kinscy, a grcat
studcnt of human bchavior and thc pionccring rcscarchcr on scxuality, oncc
said, "Thc world is not dividcd into shccp and goats . . . . aturc rarcly dcals
with discrctc catcgorics. nly thc human mind invcnts catcgorics and trics
to frcc fcts into scparatcd pigconholcs' ' To paraphrasc Kinscy, bipolar
disordcr is probably not dividcd simply into bipolar I and bipolar II, cithcr-
and paticnts ohcn don't ht into DSMpigconholcs. Thcrc is also thc fct that
many paticnts with onc psychiatric disordcr also suhcr hom anothcr-pa-
ticnts with mood disordcrs ohcn havc addiction problcms, paticnts with dc-
vclopmcntal disordcrs such as autism hcgucntly gct dcprcsscd or anxious-
not to mcntion that symptoms of onc disordcr arc ohcn sccn in anothcr.
thc "critcria fr attcntion- dchcit hypcractivity disordcr [AOHO) arc ncarly
idcntical to thosc of hypomania, fr cxamplc. Many paticnts with bipolar
disordcr also havc panic attacks, but to say that thcsc paticnts suhcr hom a
mood disordcr andan anxicty disordcr simply isn't accuratc. In fct, trcat-
ing anxious and dcprcsscd paticnts with anti- anxicty mcdications such as
clonazcpam [Klonopin) and othcr scdativcs ohcn makcs things worsc rathcr
than bcttcr.
Ior all thcsc rcasons, I am not going to list hcrc thc DSMdiagnostic cri-
tcria fr thc bipolar disordcrs. I don't want to tcmpt nonclinicians to cngagc
in sclf- diagnosis or diagnosis of fmily mcmbcrs. Thc DSMis casily availablc
in librarics, but it should bc considcrcd a rcfcrcncc book fr rcscarchcrs and
clinicians, not a tcxtbook of psychiatry.
BpoIar Catcgorcs n mc OSM-5
nly two subtypcs of bipolar disordcr havc bccn charactcrizcd wcll
cnough to havc bccn assigncd thcir own DSMcatcgorics. bipolar I and bi-
polar II As wc saw in chaptcr 2, in thc scction on bipolar spcctrum disor-
dcrs, thcrc arc probably othcr frms of thc illncss that will cvcntually bc dc-
scribcd and undcrstood wcll cnough to bc dcmarcatcd with thcir own labcls
as wcll, but fr now a paticnt having onc of thcsc "soh bipolar disordcrs
would bc diagnoscd with "bipolar disordcr not clscwhcrc classihcd [bipolar
disordcr LC) ,' according to thc DSM.Cyclothymic disordcr is includcd in
thc DSM-as a diagnosis as wcll.
1PL1V 11SLV1V i1 H DSM-j M j,
L M A 1 H J
and thc many frms thc illncss can takc, I want to takc a momcnt to rcvicw
just how fr wc'vc comc in our undcrstanding of this illncss-and whcrc
wc'vc comc }cm. I think thc undcrstanding of any subj cct is incomplctc
unlcss you know a littlc about its history, and thc history of thinking about
bipolar disordcr not only is a fscinating story in its own right but also will
providc valuablc insights into how psychiatrists vicw thc diagnostic proccss
and approach thc trcatmcnt of psychiatric disordcrs. [This is a chaptcr that
may bc of morc intcrcst to studcnts and mcntal hcalth profcssionals than to
paticnts and thcir fmilics. You can skip it without any loss of continuity.)
Bcmrc "BpoIar"
Thc ancicnt Crccks bclicvcd that all maladics of mind and body wcrc
causcd by imbalanccs among fur vital bodily huids, or "humors' nc of
thc tcrms wc still usc to dcscribc dcprcssion, mc|ancbc| |a, is dcrivcd hom
thc Crcck word fr onc of thcsc humors. black bilc. According to humoral
thcory, dcprcssion was thought to bc causcd by an cxccss of black bilc and
mania by an cxccss of ycllow bilc.
Although thcy wcrc incorrcct about thc causcs of thc two oppositc
mood statcs of bipolar disordcr, scvcral ancicnt physicians had rcmarkablc
insight into thc conncction bctwccn thcm. Arctaius of Cappadocia [ca. Iy o)
dcscribcd thc syndromc of dcprcssion i n which paticnts bccamc "pccvish,
dispiritcd, slccplcss and "complaincd] of lifc and dcsirc d] to dic' In othcr
paticnts hc dcscribcd manic symptoms. "At thc hcight of thcir] discasc thcy]
havc impurc drcams, and irrcsistiblc dcsirc s] . . . . If rouscd to angcr by ad-
monition or rcstraint, thcy bccomc wholly mad' 5ut most rcmarkably, hc
statcd, "In my opinion, mclancholia is without any doubt thc bcginning and
cvcn part of thc disordcr callcd mania'
Paul of Acgina [ 6zy -6o) madc a
similar conncction bctwccn thc two syndromcs, basing his thinking on hu-
moral thcory. Likc othcr Crccks, Paul assumcd that mclancholia was causcd
by too much ordinary black bilc, but hc postulatcd that mania was causcd by
an cxccss of "ycllow bilc which, by too much hcat,' had bccomc burncd
black bilc.
Considcrations of possiblc physical causcs fr thc symptoms of bipo-
lar disordcr morc or lcss ccascd ahcr thc fll of thc Roman Lmpirc, and thc
symptoms and bchaviors that wc now rccognizc as arising hom psychiat-
ric conditions wcrc usually attributcd to witchcrah or dcmonic posscssion
rathcr than to disruptions of a pcrson's physiology. Whcn mcdicval timcs
gavc way to thc Rcnaissancc and thc Lnlightcnmcnt, mcntal illncss again
bccamc thc purvicw of physicians rathcr than pricsts, and modcrn attcmpts
to undcrstand and classify discascs bcgan. Mclancholia and mania wcrc ohcn
considcrcd to bc two scparatc disordcrs by thcsc carly physicians. How-
cvcr, a fcw insightml clinicians, such as thc Lnglish physician Robcrt [amcs
[I;oy -I;;6) , conncctcd thc two syndromcs. "Thcrc is an absolutc cccssity
fr rcducing Mclancholy and Madncss mania] to onc Spccics of Oisordcr,
and conscgucntly considcring thcm in onc j oint Vicw . . . . Wc hnd, that
thcy both arisc hom thc samc common Causc and rigin, that is, an cx-
ccssivc Congcstion of thc 5lood in thc 5rain . . . . Wc hnd that mclancholic
Paticnts . . . casily fll into Madncss, which, whcn rcmovcd, thc Mclancholy
again discovcrs itsclf.'

Mclancholia and "madncss wcrc thought by most
carly physicians who wrotc about mcntal discasc to prcdisposc to cach othcr
but ncvcrthclcss to bc cntircly dihcrcnt conditions.
ot until thc middlc of thc ninctccnth ccntury was thc idca that dc-
prcssion and mania might bc cxprcssions of a singlc mcntal illncss hrst pro-
poscd. It was suggcstcd by two Ircnch a||cn|s|s [a tcrm-hom a||n, thc
Ircnch word fr "insanc-that was uscd in Irancc and in Lnglish- spcak-
ing countrics at onc timc to dcnotc physicians spccializing in mcntal dis-
ordcrs) . [ulcs 5aillargcr [I8o-I8o) publishcd a papcr in I8y ( dcscribing
an illncss hc callcd |a}c| |c u dcu||c}crmc, and two wccks latcr [can-Picrrc
Ialrct [ I;(-I8;o) rushcd a papcr into print in thc samc j ournal in which
hc insistcd that hc had bccn tcaching his studcnts about |a}c||cc|rcu|a|rcat
thc Salpctricrc hospital fr tcn ycars. [This was, incidcntally, thc samc hos-
pital whcrc scvcral ycars latcr thc young Sigmund Ircud bcgan to frmulatc
his own thcorics about mcntal phcnomcna. ) 5oth mcn dcscribcd a mcn-
tal illncss charactcrizcd by altcrnating pcriods of mclancholia and mania
that wcrc ohcn scparatcd by pcriods of normal mood. Ahcr thc appcarancc
of thcir original papcrs, 5aillargcr and Ialrct wrotc scvcral "mc hrst| "no,
mchrst| lcttcrs to thc Bu||c||n of thc Impcrial Acadcmy of Mcdicinc, cach
claiming to bc thc originator of this idca. Which of thcm dcscrvcs crcdit as
thc hrst to dcscribc bipolar disordcr is a mattcr upon which scholars still
disagrcc. ' 5ut mcdical historians do nc|disagrcc about thc idcntity of thc
psychiatrist who publishcd thc hrst comprchcnsivc dcscription of thc mood
disordcrs and cstablishcd thc basis of thc classihcation systcm fr mcntal
illncsscs that wc still usc today.
r. KracpcIn and "Manc-cprcssvc Insan"
It was thc Ccrman psychiatrist Lmil Kracpclin [I8y6-Iz6) who, in I8,
solidihcd thc modcrn conccpt of bipolar disordcr in thc sixth cdition of his
cnormously inhucntial tcxtbook on mcntal illncsscs, Psycb|a|r|c:|n Icbr-
|ucb}rS|ud|rcndcundArc|c.Kracpclin had bccn working fr scvcral ycars
to dcvclop a logical and comprchcnsivc classihcation systcm fr major mcn-
tal illncsscs, and succcssivc cditions of his 7cx||cc/c}Psycb|a|ry documcnt
thc dcvclopmcnt of his thinking.
In thc hhh cdition, hc dividcd scvcrc frms of mcntal illncss into two
broad catcgorics . thosc that had a dctcriorating coursc of illncss and thosc
that wcrc "pcriodic' Thcsc two groups arc still rccognizablc in modcrn
classihcations of psychiatric disordcrs, thc "dctcriorating group contain-
ing thc various frms of schizophrcnia and rclatcd disordcrs and thc "pcri-
odic group containing thc mood disordcrs. Although hc was not thc hrst
to suggcst that mania and dcprcssion wcrc both cxprcssions of onc disordcr,
Kracpclin was thc hrst to articulatc, clcarly and convincingly, thc idca that
a||disordcrs of mood wcrc rclatcd to onc anothcr . "Manic- dcprcssivc insan-
ity . . . includcs on thc onc hand thc wholc domain of so- callcd pcriodic and
circular insanity, on thc othcr hand simplc mania, and] thc grcatcr part of
thc morbid statcs tcrmcd mclancholia . . . . In thc coursc of thc ycars I havc
bccomc morc and morc convinccd that all thc abovc-mcntioncd statcs only
rcprcscnt manifcstations of a singlc morbid proccss'

Kracpclin's "manic-
dcprcssivc synthcsis was a major brcakthrough in thc undcrstanding and
classihcation of major mcntal illncsscs. "
5ut Kracpclin was morc than an acadcmic and a thcorctician, hc was a
clinician who saw cnormous numbcrs of paticnts and rccordcd his obscr-
vations of thcir illncsscs in supcrb dctail. As you know hom rcading thcm
in prcvious chaptcrs, his dcscriptions of thc symptoms of bipolar disordcr
arc vivid and insightml, and thcy havc ncvcr bccn surpasscd. A frmcr pro-
fcssor oncc told mc that "anyonc who thinks thcy'vc discovcrcd somcthing
ncw in psychiatry simply hasn't rcad thc Ccrman psychiatric litcraturc' I
think it's fir to say that anyonc who thinks hc has discovcrcd somcthing
ncw about bipolar disordcr-at lcast, about its symptoms and diagnosis-
simply hasn't rcad Kracpclin.
Kracpclin's contributions, although trcmcndously signihcant fr thosc
intcrcstcd i n thc classihcation of mcntal disordcrs, ohcrcd littlc practical
bcncht in his timc to thosc amictcd with thcm. I would imaginc that Or.
Kracpclin's paticnts wcrc morc accuratcly infrmcd about thcir illncss than
most paticnts of that timc and had morc rcliablc prognostic infrmation,
but thcrc was rcally nothing hc could do to hclp thcm with thcir symptoms.
Thcrc was still no trcatmcnt fr anypsychiatric condition that ohcrcd much
hopc of allcviating thc symptoms or altcring thc coursc of thc discasc. Al-
though thc Lnglish translation of thc chaptcr on "manic-dcprcssivc insan-
ity in thc cighth cdition of Kracpclin's tcxtbook is morc than two hundrcd
pagcs long, thc " Trcatmcnt scction is lcss than hvc pagcs long-and most of
that consists of warnings about thc suicidal bchaviors of dcprcsscd paticnts
and cautions against discharging thcm too soon hom thc hospital. In thc
abscncc of trcatmcnts fr manic- dcprcssivc illncss, paticnts spcnt months,
cvcn ycars, in hospitals and asylums .
As thc study of mcntal disordcrs cntcrcd thc twcnticth ccntury, hopcs
fr morc chcctivc trcatmcnt of psychiatric disordcrs rosc whcn scicntihc
discovcrics shcd somc light on thc causcs of scvcral mcntal illncsscs. In Io6
thc Ccrman microbiologist August Wasscrmann discovcrcd a mcthod to
dctcct in human spinal huid antibodics to thc microorganism that causcs
syphilis . This may not sound likc a discovcry that had anything to do with
psychiatry, unlcss you know that syphilitic infcction of thc ccntral ncrvous
systcm was at this timc onc of thc most common causcs of scvcrc psychiatric
symptoms, and that ncarly half of thc paticnts in mcntal institutions suhcrcd
hom "gcncral parcsis of thc insanc,' as syphilis with psychiatric manifcsta-
tions was known. With thc dcvclopmcnt of thc Wasscrmann tcst, it bccamc
possiblc to diagnosc thc illncss with a vcry high dcgrcc of rcliability. Ior thc
hrst timc, a causc of a frm of "madncss had bccn discovcrcd. That samc
ycar anothcr Ccrman microbiologist, Paul Lhrlich, dcvclopcd thc hrst chcc-
tivc trcatmcnt fr syphilis, using arscnic compounds. Although thc trcat-
mcnt was crudc and dangcrous, it was chcctivc cnough in thc carly stagcs
of thc discasc to rcducc thc incidcncc of thc illncss by yo pcrccnt in scvcral
Luropcan countrics.
Wc hardly think of syphilis as a mcntal illncss today, but paticnts with
syphilitic infcction of thc brain can suhcr hallucinations, dclusions, and
mood changcs not vcry dihcrcnt hom thosc sccn in bipolar disordcr and
schizophrcnia. An carly-twcnticth-ccntury psychiatric tcxt dcscribcs thc
mania- likc cxcitcmcnt that was somctimcs sccn in pcrsons with ccntral ncr-
H ALL1 11SS M 1
vous systcm syphilis. "Thc intcnsity of thc cxcitcmcnt is cxtrcmc, thcrc is
absolutc slccplcssncss and] inccssant rcstlcssncss. Thc grandiosc dclusions
arc thc controlling fcaturc of thc parctic's thought. Thc paticnt . . . comcs bc-
frc us trcmulous with cmotion, his cyc bright, as thc ovcrpowcring visions
of wcalth and grandcur hoat bcfrc his mind' Thc discovcry of rcliablc and
chcctivc diagnostic tcchnigucs fr gcncral parcsis of thc insanc-unfrtu-
natcly, arscnicals had littlc chcct on thc advanccd ccntral ncrvous systcm
discasc-was sccn by many as an cnormous advancc in thc undcrstanding
of psychiatric disordcrs. Clinicians chargcd with thc carc of psychiatric pa-
ticnts had grcat hopcs that thc causcs of othcr psychiatric disordcrs would
soon bc fund.
As morc and morc powcrml microscopcs wcrc invcntcd and spccial tis-
suc stains wcrc dcvclopcd fr brain tissucs, various microscopic structurcs
of thc brain-thc many dihcrcnt typcs of ncurons and thc microscopic ar-
chitccturc of thc dihcrcnt parts of thc brain-bccamc visiblc fr thc hrst
timc. Anatomical and chcmical abnormalitics wcrc fund to charactcrizc
scvcral othcr discascs with promincnt mcntal symptoms. In Io6 thc Swiss
ncuropathologist Alois Alzhcimcr, who was a studcnt of Kracpclin, discov-
crcd abnormal microscopic plagucs and tanglcs of ccllular dcbris in thc
brains of pcrsons who had dicd hom thc progrcssivc brain discasc that was
cvcntually namcd fr him. Individuals with crc||n|sm, a particularly scvcrc
frm of mcntal rctardation, wcrc fund to havc abnormally low lcvcls of thy-
roid hormoncs. In IIy c||ayra,anothcr mystcrious discasc charactcrizcd by
skin lcsions and gradual mcntal dctcrioration, was discovcrcd to bc causcd
by a dchcicncy of vitamin 5.
5ut blood tcsts and brain studics rcvcalcd nothing about manic- dcprcs-
sivc illncss. Try as thcy might, pathologists and anatomists could hnd noth-
ing dihcrcnt or abnormal in thc brain structurcs of individuals with bipolar
disordcr, using thc tools that wcrc availablc to thcm.
cw ways of thinking sccmcd ncccssary to undcrstand thc mcntal ill-
ncsscs fr which no physical causc could bc fund, and shortly ahcr thc
bcginning of thc twcnticth ccntury, ncw thcorics wcrc advanccd, most no-
tably by Sigmund Ircud, that sccmcd to havc considcrablc powcr to cxplain
thc basis of thcsc still- mystcrious illncsscs. Thcsc thcorics, boilcd down to
thcir csscncc, hcld that mcntal symptoms wcrc rcactions to lifc cvcnts in vul-
ncrablc individuals-not discasc statcs causcd by disruptions in biological
mnctioning. Thc ncw thcorics of mcntal illncss instructcd psychiatrists to
usc "talking curcs to trcat thcir paticnts .
5y carcmlly cxploring paticnts' biographics in minutc dctail, physicians
attcmptcd to undcrstand what conhicts and lifc cvcnts thcir paticnts wcrc
rcacting to with symptoms of dcprcssion or mania. It was thc cxpcctation
that thc propcr combination of undcrstanding, rcintcrprctation, and cn-
couragcmcnt could allcviatc paticnts' symptoms. Ircud, morc than any othcr
carly psychiatrist, dcvclopcd claboratc thcorics about normal and abnormal
childhood psychological dcvclopmcnt that hc fclt could cxplain why somc
pcoplc dcvclopcd cxtrcmc psychological symptoms in rcsponsc to dimcult
lifc situations and cvcnts whilc othcrs did not. Manic- dcprcssivc illncss and
schizophrcnia camc to bc callcd }unc||cna||||ncsscsbccausc it was bclicvcd
that paticnts with dcprcssion or mania or symptoms of schizophrcnia had
ncrma|brain and ncrvous systcm mnctioning. Although Ircud and his dis-
ciplcs did not totally discount biological agcnts as having somc rolc in thc
causation of thcsc problcms, thcy did not scc thcir paticnts as suhcring hom
d|scascs.A "mnctional illncss was bclicvcd to bc an illncss of thc mind, not
of thc brain. Thcsc conccpts dominatcd Amcrican psychiatry until wcll into
thc I6os.
Ouring thcsc dccadcs most psychiatrists bclicvcd that abnormal mcn-
tal phcnomcna wcrc causcd by traumatic childhood cvcnts, poor parcnting,
rcprcsscd scxual fcclings, and intcrpcrsonal conflicts. Thcy lost intcrcst in
thc classihcation and catcgorization of psychiatric illncsscs, thc vcry idca of
trying to makc a diagnosis in a psychiatric paticnt sccmcd a wastc of timc
bccausc thc frm as wcll as thc causc of a psychiatric problcm sccmcd to bc
as individual as thc biography of thc paticnt i n whom it occurrcd. Thcn in
I( an unknown Australian psychiatrist publishcd an articlc in thc Mcd|-
ca|)curna|c}Aus|ra| |acallcd "Lithium Salts in thc Trcatmcnt of Psychotic
r. Cadc and Lthum
5y thc I os and I(os, most physicians intcrcstcd in thc trcatmcnt of
mcntal disordcrs had j oincd psychoanalytic institutcs to lcarn thc thcory
and practicc of psychiatry according to thc tcachings of Ircud and his fl-
lowcrs. Thcy traincd and practiccd mostly in thc big citics, mostly trcating
paticnts with mild dcprcssion or anxicty, paticnts who had thc timc, mo-
tivation, and moncy to attcnd thcrapy scssions fur or hvc days a wcck, to
cxplorc thcir past and rcintcrprct thcir prcscnt to bccomc hcalthicr, happicr,
and bcttcr "adjustcd' Thc thcorics of Ircud rcvolutionizcd thc undcrstand-
ing of many aspccts of human bchavior, and thcy continuc to frm thc basis
fr thc practicc of psychothcrapy. 5ut thcrc wcrc many paticnts who bcnc-
htcd littlc hom thcsc ncw idcas. Thcy wcrc thc paticnts Or. Kracpclin had
carcd fr. thc victims of schizophrcnia and manic- dcprcssivc illncss.
Ior thcsc paticnts, houscd fr months or ycars in [mostly public) hos-
pitals and asylums, thc thcrapcutic armamcntarium had not changcd much
in two hundrcd ycars. bcd rcst fr thc dcprcsscd, physical rcstraint fr thc
agitatcd, baths, tranguilization with morphinc and bromidcs, and thc usc of
H ALL1 11SS M j
licuar- I [ohn [. Cadc.
Scurce Statc Lbrary oI Vctora.
numcrous othcr substanccs thought to havc bcnchcial chccts, among thcm
guininc and cvcn cod-livcr oil. onc of thcsc intcrvcntions had any but thc
most insignihcant chccts on scrious mcntal illncss.
[ohn [. Cadc, M.O. , scnior mcdical omccr in thc Mcntal Hygicnc Oc-
partmcnt of Victoria, Australia, was convinccd that manic- dcprcssivc illncss
was a biological disordcr, not a psychological onc [hgurc (-I) . Working in
his laboratory to dctcrminc whcthcr somc toxin might bc prcscnt in thc
urinc of paticnts with manic- dcprcssivc illncss, Cadc bccamc cspccially in-
tcrcstcd in urca and uric acid, by-products of protcin mctabolism fund in
urinc. Hc was tcsting thc toxicity of thcsc compounds by inj ccting small
amounts of thcm into guinca pigs.
nc of thc tcchnical problcms with this work was that uric acid is rathcr
insolublc in watcr, making it dimcult to prcparc inj cctablc solutions at high
conccntrations. Looking fr a solublc uratc salt to usc instcad of uric acid,
Cadc consultcd prior rcscarch and discovcrcd that uric acid was casicst to
dissolvc in watcr whcn it was combincd with a lithium ion as lithium uratc.
Hc inj cctcd small amounts of lithium uratc into thc guinca pigs and noticcd
that uric acid sccmcd to bc much lcss toxic in this frm. Tis suggcstcd to
Cadc that thc lithium componcnt of thc compound might havc somc sort
of protcctivc chcct against uratc toxicity. To dctcrminc what thc chcct of thc
lithium ion might bc, hc inj cctcd lithium carbonatc-thc carbonatc ion is
harmlcss and is fund in substanccs such as baking soda-and discovcrcd
that "ahcr a latcnt pcriod of about two hours thc animals, although mlly
conscious, bccamc cxtrcmcly lcthargic and unrcsponsivc to stimuli fr onc
to two hours bcfrc oncc again bccoming normally activc'

Cadc admits in his original papcr that "it may sccm a long distancc hom
lcthargy in guinca pigs to cxcitcmcnt in psychotics,' but asylum doctors of
thc timc wcrc dcspcratc fr ncw trcatmcnt possibilitics, so Cadc dccidcd to
administcr lithium prcparations to scvcral paticnts who wcrc chronically
agitatcd. Thc chcct on paticnts with mania was dramatic.
Casc I-W. 5. , a malc agcd hhy- onc ycars, who had bccn in a statc of
chronic manic cxcitcmcnt fr hvc ycars, rcstlcss, dirty, dcstructivc,
mischicvous and intcrfcring, had long bccn rcgardcd as thc most
troublcsomc paticnt in thc ward. His rcsponsc was highly gratiing.
Irom thc start of trcatmcnt on March z, I(8, with lithium citratc hc
stcadily scttlcd down and in thrcc wccks was cnj oying thc unaccus-
tomcd surroundings of thc convalcsccnt ward. As hc had bccn ill so
long and conhncd to a "chronic ward,' hc fund normal surroundings
and libcrty of movcmcnt strangc at hrst. Hc rcmaincd pcrfcctly wcll
and lch thc hospital on indchnitc lcavc with instructions to takc a
dosc of lithium carbonatc, hvc grains, twicc a day. Hc was soon back
working at his old job. Howcvcr, hc bccamc morc lackadaisical about
his mcdicinc and hnally ccascd taking it. His rclativcs rcportcd that
hc had not takcn any fr at lcast six wccks prior to his rcadmission on
[anuary jO, I( and was bccoming stcadily morc irritablc and crratic.
n rcadmission to thc hospital hc was at oncc startcd on lithium car-
bonatc, tcn grains thrcc timcs a day, and in a frtnight had again sct-
tlcd down to normal. Hc is now [Icbruary z8, I() rcady to rcturn to
homc and work.
Casc VIII-W. M. , a man of hhy ycars, was suhcring hom an
attack of rccurrcnt mania, thc hrst of which hc had had at thc agc of
twcnty. Thc prcscnt attack had lastcd two months and showcd no signs
of abating. Hc was garrulous, cuphoric, rcstlcss and unkcmpt whcn hc
startcd taking lithium. Two days latcr hc was rcportcd to bc guictcr.
5y thc ninth day hc was dchnitcly scttling down and thc fllowing
day commcnccd work in thc gardcn. 5y thc cnd of two wccks hc was
practically normal-guict, tidy, rational, with insight into his prcvious
condition. This was in markcd contrast to his condition a frtnight
bcfrc whcn hc had to bc lockcd in a singlc room at night . . . and was
H ALL1 11SS M j
too rcstlcss to cat in thc dining room owing to his unscttling chcct on
thc othcr paticnts.

Or. Cadc had trcatcd tcn manic paticnts with lithium, and all tcn had shown
thc samc dramatic improvcmcnt. Hc had also givcn lithium to six paticnts
with "dcmcntia praccox [schizophrcnia) and thrcc paticnts with "chronic
dcprcssivc psychoscs,' but with lcss chcct. Thc agitatcd paticnts with schizo-
phrcnia bccamc lcss agitatcd but had "no mndamcntal improvcmcnt, thc
dcprcsscd paticnts had "no improvcmcnt'
It is ohcn cmphasizcd in tcxtbooks and articlcs on thc history oflithium
trcatmcnt that Cadc's discovcry of lithium`s cmcacy in bipolar disordcr was
purc accidcnt-an obscrvation that misscs an important point. Cadc, likc
many hospital psychiatrists, but unlikc pcrhaps many othcr psychiatrists of
his timc, was pursuing a biological intcrvcntion fr what hc bclicvcd was
a biological disordcr. His casc dcscriptions rcvcal that cvcn though hc had
littlc spccihc thcrapy to ohcr thcm, hc had takcn a complctc history of his
paticnts' coursc of illncss, carcmlly cxamincd thcm, and, fllowing in thc
fotstcps of Lmil Kracpclin, madc a d|aycs|sbascd on his cxamination and
history- taking. Cadc's approach to thcsc scvcrcly ill paticnts-his assump-
tion that thcy suhcrcd hom discascs rathcr than hom cmotional rcactions-
providcd thc thcorctical undcrpinning that madc his discovcry possiblc. A
psychiatrist who bclicvcd in "rcactions and "mnctional illncss would havc
bccn unlikcly to dividc paticnts into thc diagnostic catcgorics of mania,
schizophrcnia, and dcprcssivc psychosis and rcport on thc dihcrcntial cm-
cacy of a pharmaccutical in cach group. Such a psychiatrist would havc bccn
cvcn lcss likcly to look fr toxins in thc urinc of paticnts with mania. '"
nc would think that thc ncws of Cadc's discovcry would havc sprcad
likc wildhrc. It did not. In fct, scvcral dccadcs clapscd bcfrc lithium was
approvcd fr thc trcatmcnt of bipolar disordcr by thc L. S. Iood and Orug
Administration. Why this incrcdiblc dclay
Part of thc rcason was thc statc of world psychiatry fllowing thc cnd
of World War II Ccrman psychiatry, which had produccd supcrb clinicians
likc Kracpclin and Ircud and many othcr pionccrs in thc scicncc of mcntal
disordcrs, was in ruins, litcrally and hgurativcly. Thc Ccrman psychiatric
cstablishmcnt had bccn mcsmcrizcd by thc azi movcmcnt, and promincnt
Ccrman psychiatrists had cnthusiastically participatcd in thc cxpulsion of
[cwish collcagucs hom thc profcssion and cvcn in thc murdcr of thc paticnts
thcy had bccn chargcd to carc fr. Thousands of mcntally rctardcd and mcn-
tally ill individuals wcrc gasscd in thc ycars lcading up to thc war and during
thc war. Whcn Cadc wrotc of his work with lithium, Ccrmany was no longcr
providing lcadcrs in psychiatric mcdicinc, rathcr, Ccrman psychiatry was in
dirc nccd of rchabilitation.
i i
In thc Lnitcd Statcs and Lngland, psychoanalytic thcorics had rcplaccd
thc traditional mcdical practiccs of cvaluation, diagnosis, and trcatmcnt
with thc prcscription of thc "talking curc fr all cmotional problcms. Accu-
ratc psychiatric diagnosis simply didn`t cxist, any paticnt with scvcrc symp-
toms was usually callcd "schizophrcnic and admittcd to a statc psychiatric
hospital fr littlc morc than custodial carc. Ronald Iicvc, thc Amcrican psy-
chiatrist who championcd thc usc oflithium in thc Lnitcd Statcs in thc I;os
and who was instrumcntal in gctting Amcrican psychiatrists to prcscribc
i t fr thcir paticnts, obscrvcd that during thc latc I(os and thc Iyos in
cw York, hc "rarcly mct with thc diagnosis of manic-dcprcssion . . . . It had
virtually disappcarcd. Most cascs of cxcitablc, talkativc, and clatcd bchavior
wcrc bcing diagnoscd as schizophrcnia' ' '
5ut a Oanish psychiatrist, Morgans Schou, rcalizcd that Cadc's discov-
cry rcprcscntcd a rcal brcakthrough. Hc notcd in a Iy ( papcr, "It is rathcr
astonishing that Cadc's] obscrvation has filcd to arousc grcatcr gcncral in-
tcrcst among psychiatrists'
Schou and his collcagucs did thc carcml clini-
cal trials that cvcntually rcsultcd in thc dcvclopmcnt of rccommcndcd dos-
agcs and prcparations of lithium fr thc trcatmcnt of symptoms of bipolar
disordcr. Pcrhaps morc than any othcr clinical rcscarchcr, Schou cstablishcd
thc cmcacy of lithium trcatmcnt fr mania. Lvcn morc important was his
discovcry that lithium could prcvcnt thc rccurrcncc of symptoms in paticnts
with bipolar disordcr.
In Iy; anothcr brcakthrough occurrcd in thc trcatmcnt of mood dis-
ordcrs whcn Roland Kuhn, a Swiss psychiatrist, dcscribcd how a compound
originally dcvclopcd as an antihistaminc had rcmarkablc chccts on dc-
prcsscd paticnts. Hc rcportcd his rcsults in a Swiss mcdical j ournal, and his
papcr was rcprintcd thc ncxt ycar in Lnglish as " Thc Trcatmcnt of Ocprcssivc
Statcs with C zzyy [Imipraminc Hydrochloridc) ' 5ut Kuhn also noticcd
that in somc paticnts imipraminc simply rcplaccd onc mood problcm with
anothcr. "In markcd manic-dcprcssivc psychosis, i. c. , if thc dcprcssions arc
casily and hcgucntly rcplaccd by manic-likc phascs or actual manic statcs,
thc rcaction is lcss fvorablc . . . . Thc tcndcncy ariscs fr thc dcprcssion to
switch ovcr into a manic phasc'
i +
I n onc of thcir hrst papcrs on thc usc oflithium in manic paticnts, Schou
and his collcagucs had pointcd out that "thc bcnchcial chcct of lithium in
cascs of mania appcars to ohcr ncw possibilitics fr a study of thc a|bcbys-
|c|cg i. c. , thc discasc mcchanism] of thc manic- dcprcssivc psychoscs'
Thc discovcry of thc thcrapcutic chccts of imipraminc on dcprcsscd paticnts
and thc obscrvation that it could prccipitatc mania in paticnts with "man-
ic- dcprcssivc psychosis wcrc two morc clucs that bipolar disordcr might bc
morc than a psychological "rcaction'
Thc fct that a chcmical [lithium) madc thc symptoms of mania go away
H ALL1 11SS M ,
indicatcd that mania had at lcast somc biochcmical basis. Thc discovcry of
thc dihcrcnt chccts of imipraminc on dcprcsscd pcrsons with and without a
history of mania rcinfrccd thc discasc modcl fr bipolar disordcr. Pcrsons
with a history of mania bccamc manic if thcy took imipraminc, pcrsons who
did not havc a history of mania [usually) did not. Imipraminc was not sim-
ply a "manio- gcnic drug, a drug that produccd cuphoria in cvcryonc who
took it. Thc fct that only bipolar individuals bccamc manic hom it sug-
gcstcd that thcir illncss had a dihcrcnt biochcmical basis hom othcr cascs
of dcprcssion. Thc modcrn agc of psychiatry had bcgun, as had thc scarch
fr morc and bcttcr pharmaccutical trcatmcnts and fr thc physical basis of
thcsc disordcrs.
A H 1
Scvcral ycars ago I hcard a classical guitarist bcing intcrvicwcd on
thc radio. Hc said hc was ohcn askcd by strangcrs, usually pcoplc
who didn't know much about classical music, whcthcr hc playcd thc
c|cc|r|cor thc accus||cguitar. "I hatc that tcrm, accus||cyu||ar.I'd
rathcr just say I playcd thc guitar,' hc said. "5ut ahcr thc clcctric guitar
was invcntcd, I supposc somcbody had to comc up with a tcrm fr a
non- clcctric guitar'
Thcrc is a tcrm fr psychiatric problcms that many nonpsychia-
trists usc that I dislikc, and that's cbcm|ca||m|a|ancc.It's a tcrm that
wc startcd hcaring uscd in thc I;os to dcscribc psychiatric problcms
that wcrc not psychological rcactions or "mnctional problcms [as I
dcscribcd thcm in chaptcr () but rathcr wcrc illncsscs causcd by somc
malmnction of brain physiology. To paraphrasc thc guitarist, I supposc
somcbody had to invcnt a tcrm fr psychiatric illncsscs as opposcd
to purcly psychological conditions, but cbcm|ca||m|a|anccimplics scv-
cral things about psychiatric illncsscs that arc vcry mislcading.
Iirst is thc idca that all disturbanccs of mcntal lifc fll into two
mutually cxclusivc catcgorics. "chcmical and "nonchcmical [or
pcrhaps "chcmical and "psychological might work bcttcr) . As wc
shall scc in this ncxt group of chaptcrs, such a division is not possi-
blc, bccausc thc "chcmical and "psychological aspccts of mcntal lifc
intcract and ovcrlap. Sccond, to say that a psychiatric problcm likc
bipolar disordcr is simply an "imbalancc of brain chcmicals is a mon-
umcntal ovcrsimplihcation of what rcally lics at thc root of thcsc prob-
lcms. Thc fntastically complcx human brain i s not simply a canta-
loupc-sizcd organ bathcd in a soup of "chcmicals that can bc adjustcd
by thc addition of mcdications to achicvc a "balancc [as a chcf adds a
littlc morc salt or anothcr pinch of caycnnc to makc a fvoritc rccipc
comc out right) .
In chaptcr I'll do my bcst to cxplain what causcs bipolar disor-
dcr and also touch on how wc think thc mcdications uscd to trcat thc
illncss work. Thc dctails hcrc arc a bit complicatcd, but thc basics arc
not dimcult to grasp. This chaptcr might rcguirc a slowcr, morc carcml
rcading pacc fr thosc unfmiliar with tcrms likc ncurc|ransm|||crs,
but thc chort will pay oh latcr, allowing you to undcrstand thc usc of
mcdications in bipolar disordcr much bcttcr.
Thcn in subscgucnt chaptcrs wc'll talk about trcatmcnt morc spc-
cihcally, bcginning with a rcvicw of thc pharmaccuticals uscd in thc
trcatmcnt of thc disordcr. Wc'll also covcr clcctroconvulsivc thcrapy
and othcr ncwcr brain-stimulation tcchnigucs and, last but ccrtainly
not lcast, thc important rolc of counscling and psychothcrapy in thc
trcatmcnt of thc illncss. Wc' ll cnd part II with a bricf ovcrvicw of thc
trcatmcnt approachcs and somc principlcs of trcatmcnt that I think arc
important to rcmcmbcr.
,0 M VAi
O I1dS11C 1d1D
L M A 1 H

if that scntcncc scnds shivcrs up your spinc, you can skip this chaptcr. You'll
still bc ablc to undcrstand thc chaptcrs that fllow. Although no onc rcally
knows fr surc cxactly what causcs bipolar disordcr, wc havc somc thcorics,
bascd on rcscarch, that makc scnsc. If you arc intcrcstcd in thosc thcorics,
rcad on. If you'rc not, you can skip ahcad to thc mcdication chaptcrs.
Somc ycars ago, thc psychiatrist and ncuroscicntist ancy Andrcascn
wrotc a book, 7cBrc/cn Bra|n,' about thc ncw discovcrics in biological
psychiatry. Thc titlc makcs thc point that psychiatric illncsscs such as bi-
polar disordcr and schizophrcnia arc causcd by biological malmnctions of
thc brain, not by rcprcsscd mcmorics or traumatic childhoods. Although
wc still don`t know cxactly what thosc malmnctions arc, wc arc gctting vcry
closc to undcrstanding somc of thc biological mcchanisms that might bc
involvcd. I n this ovcrvicw of brain mnctioning, I want t o tcll you about what
scicntists think might bc "brokcn`' in bipolar disordcr.
Many pcoplc imaginc that thc human brain is a kind of wondcrml com-
putcr. Although this is a vast ovcrsimplihcation of thc truc capabilitics of
thc brain, it's a good placc to start in trying to undcrstand how this fntastic
organ of thc mind works.
Likc thc computcr that I'm using to writc thcsc words, a human brain
rcccivcs input, proccsscs thc infrmation it rcccivcs, and thcn dclivcrs out-
put. Likc a computcr, it storcs infrmation and ohcn uscs this storcd infr-
mation to hclp proccss mrthcr input. Thc human brain rcccivcs its input
licuar-I Synapsc.
Na0|OI |a0sm|IIa|
| 0vas| c| a
Sy0apI| cc| aII
Na|va I | ba|


. Sy0apsa
hom thc scnsc organs-thc cycs, cars, tastc buds, touch rcccptors, and so
frth-and dclivcrs output in tcrms of bchavior.
You may know that a computcr computcs by mcans of many thousands
of microscopic switchcs cmbcddcd in its proccssing chip. Thc pattcrn of "on
and "oh in thc switchcs is what storcs infrmation, thc control of thc flow of
signals through thcsc switchcs is thc proccssing. Thc human brain contains
about II billion ncrvc cclls, or ncurcnsbutas powcrml as a computcr with
II billion switchcs might bc, our brain is many ordcrs of magnitudc morc
imprcssivc than that. This is bccausc thc ncuron is not just a switch that is
cithcr "on or "oh,' but rathcr is an imprcssivc microproccssor in its own
right. Lach ncuron rcccivcs input hom many othcr ncurons, proccsscs this
infrmation, and scnds output to many othcrs. Thc brain, thcn, is not likc a
computcr with billions of switchcs, it is morc likc thc Intcrnct. a nctwork of
billions of computcrs, all capablc of bcing individually programmcd. Lach
ncuron in thc brain may rcccivc input and thcn transmit signals to up to hhy
thousand othcr ncurons. Thc numbcr of all thc possiblc conncctions in thc
human brain is incomprchcnsibly largc, a hypcrastronomical numbcr on thc
ordcr of thc numbcr of molcculcs in thc univcrsc.
I' m going to jump thc gun a littlc and tcll you that thcrc is a lot of cvi-
dcncc that bipolar disordcr [and pcrhaps all mood disordcrs, as wcll as anx-
icty disordcrs) is causcd by somc dcfcct in thc mcchanisms by which thc
individual ncurons arc programmcd. curons havc thc ability to bc "rcpro-
grammcd in rcsponsc to various situations [strcss is onc) , this capability is
callcd ncurc|as||c||y [rcmcmbcr that thc original mcaning of |as||crcfcrs
to a matcrial that can bc shapcd and rcshapcd, likc modcling clay) . 5ut bc-
frc wc gct to that, wc nccd to talk about ncurotransmittcrs.
Although thc human ncrvous systcm uscs clcctrical signals to do much
of its work, it uscs chcmical signals as wcll, molcculcs callcd ncurc|rans-
m|||crs arc thc mcans by which ncrvc cclls communicatc with cach othcr.
curons scnd thcsc chcmical signals to cach othcr at thc synasc, an arca
whcrc two ncurons ncarly touch. Thc hrst ncuron rclcascs ncurotransmit-
tcrs, which flow across this narrow spacc to link up with targcts callcd rccc-
|crson thc ncxt ncuron [hgurc y- I ) . Whcn cnough of thc rcccptors arc oc-
cupicd by ncurotransmittcr molcculcs, which ht into thc rcccptors likc kcys
ht into locks, thc rccipicnt ncrvc ccll is activatcd and hrcs oh its own signal.
Thcrc nccds to bc somc mcchanism fr this signaling systcm to bc turncd
oh and rcsct, of coursc. Ahcr ncurotransmittcr molcculcs link up with rc-
ccptors across thc synapsc, thcy must somchow bc rcmovcd in prcparation
fr thc ncxt batch. This happcns in a varicty of ways in dihcrcnt cclls, but
onc of thc most important mcchanisms is by rcuptakc into thc ncuron that
rclcascd thcm. A rcu|a/cum on this ncuron rcmovcs ncurotransmittcr
H P1S1L V1i M ,j
molcculcs hom thc synapsc and transports thcm back into thc intcrior of
thc ccll, whcrc thcy can bc rcpackagcd fr rcrclcasc.
curons arc continually communicating with cach othcr. curotrans-
mittcr molcculcs passing hom onc ncuron to anothcr across synapscs main-
tain a stcady tonc of chcmical signal, with thc signal gctting strongcr, or
pulsing up, at timcs and thc ncuron dctccting and rcacting to thcsc pulscs.
Thus, as I notcd carlicr, ncurons arc not just switchcs that can only bc sct to
"on or "oh but rathcr arc tiny infrmation-proccssing units that arc con-
stantly communicating with othcr ncurons to which thcy arc mnctionally
Soon ahcr Roland Kuhn discovcrcd that C 22j was an chcctivc anti-
dcprcssant [scc chaptcr (), ncuroscicntists startcd to invcstigatc thc chcct of
this pharmaccutical on brain chcmistry. Thcy discovcrcd that imipraminc is
a powcrml inhibitor of onc typc of rcuptakc pump, blocking thc rcuptakc of
a group of ncurotransmittcrs callcd ncurcycn|cam|ncs[or ncurcam|ncs). Rc-
mcmbcr that ncurons turn oh thcir chcmical signals ["turn down is prob-
ably morc accuratc) by scooping up ncurotransmittcr molcculcs hom thc
synapsc and rcpackaging thcm. [ust as partly closing thc drain in a bathtub
whilc thc watcr is running will causc thc tub to bcgin to hll, if you block
thc rcuptakc of ncurotransmittcr molcculcs into cclls, thc nct chcct will bc
an incrcasc of ncurotransmittcrs in thc synapsc. curoscicntists fund that
ncarly all thc mcdications that arc chcctivc antidcprcssants causc a block-
adc of ncurotransmittcr rcuptakc in brain cclls. This obscrvation lcd to thc
"aminc hypothcsis of thc mood disordcrs. This thcory basically statcd that
dcprcssion was causcd by an abnormally low lcvcl of thc ncurotransmittcr
ncrc|ncbr|ncand that mania was causcd by too high a lcvcl. [This may bc
whcrc thc unfrtunatc tcrm cbcm|ca||m|a|ancchad its origins. )
Iurthcr work soon indicatcd, howcvcr, that too littlc norcpincphrinc was
too simplistic an cxplanation. As morc antidcprcssant mcdications wcrc dis-
covcrcd, rcscarchcrs fund that somc vcry chcctivc oncs sccmcd to havc
littlc chcct on norcpincphrinc. Iluoxctinc [Prozac) is onc of a fmily of
pharmaccuticals that arc powcrml inhibitors of thc rcuptakc of a dihcrcnt
ncurotransmittcr, scrc|cn|n,thcy havc vcry littlc dircct chcct on norcpincph-
rinc. thcr antidcprcssants sccm to ahcct yct othcr ncurotransmittcrs.
Anothcr argumcnt against a simplistic thcory involving too much or
too littlc norcpincphrinc comcs hom an obscrvation about thc timc coursc
of thcsc chcmical changcs in thc brain. Antidcprcssant- induccd changcs in
ncurotransmittcr lcvcls at thc synapsc occur almost immcdiatcly ahcr thc
drug is takcn-in a mattcr of hours. 5ut, as is wcll known, it takcs scvcral
wccks fr thcsc agcnts to start allcviating thc symptoms of dcprcssion. If thc
problcm wcrc simply too littlc ncurotransmittcr in thc synapscs of ccrtain
brain circuits, why would it takc scvcral wccks ahcr thc drug raiscd ncu-
,q M VAi
rotransmittcr lcvcls at thc synapsc fr thc symptoms of dcprcssion to im-
provc Wc now bclicvc that antidcprcssant trcatmcnt, by artihcially changing
lcvcls of ncurotransmittcrs in thc brain, triggcrs somc rcaction in ncurons
that cnhanccs ncuroplasticity, a rcaction that takcs wccks to occur.
It has bccn shown in animal studics that ahcr scvcral wccks of cxpo-
surc t o an antidcprcssant drug, thcrc i s an incrcasc i n thc proccss by which
stcm cclls in thc brain dcvclop into maturc ncurons. Thcsc ncw ncurons
must thcn intcgratc thcmsclvcs into brain circuits. Thc rcason antidcprcssant
mcdications takc scvcral wccks to work is that it simply takcs timc fr thcsc
ccllular proccsscs to play out. This chcct is thc most dramatic in an arca of
thc brain callcd thc b|ccamus, a brain ccntcr known to bc important in
thc rcgulation of cmotions.
Antidcprcssants changc ncurotransmittcr lcvcls in thc brain, but that
is just a hrst stcp, thc triggcr fr morc complicatcd changcs that involvc thc
growth of ncw ncurons and also thc sprouting of ncw conncctions bctwccn
ncrvc cclls.
5ccausc of thc uniguc thcrapcutic chccts of lithium in bipolar disordcr,
thcrc has naturally bccn a lot of chort to hgurc out whcrc this mcdication is
activc in thc brain and what its chcct is on brain chcmistry. Lithium docsn`t
sccm to ahcct ncurotransmittcr lcvcls in thc synapsc and docsn't intcract
with ncurotransmittcr rcccptors or ahcct thc rcuptakc pumps. In fct, it has
nonc of thc typcs of dircct chccts on cclls that thc antidcprcssants havc. nly
in thc past fcw ycars has thc probablc sitc of lithium action bccn fund, and
it's not at thc synapsc at all. Lithium [and pcrhaps thc ncwcr mood stabi-
lizcrs as wcll) sccms to work at a dihcrcnt ccllular lcvcl. |ns|dcthc ncuron.
Scvcral small molcculcs insidc thc ncuron, with odd namcs likc 5OI [fr
brain- dcrivcd ncurotrophic fctor) and CRL5 [fr cAMP rcsponsc clcmcnt
binding protcin), arc thought to bc vcry important fr maintaining ncuro-
plasticity. Lithium has bccn fund to havc dramatic chccts on thc lcvcls of
thcsc molcculcs in ncurons.
Thcrc is also incrcasing intcrcst in anothcr ncurotransmittcr, y|u|ama|c,
which docsn't sccm to bc ahcctcd by antidcprcssants at all, although it is
ahcctcd by lamotriginc [Lamictal) and othcr mood stabilizcrs, glutamatc
sccms to bc vcry important in ncuroplasticity.
nc way to think about ncuroplasticity is that it undcrlics thc brain`s rc-
sponsivcncss to thc cnvironmcnt and its ability to rcact to changc and strcss.
curoplasticity is also thought to bc involvcd in mcmory and lcarning. If
you considcr thc symptoms of bipolar disordcr, which includc thinking and
conccntration problcms in addition to mood changcs, and considcr how cp-
isodcs of thc illncss can bc triggcrcd by strcsscs of various typcs, this idca
that ncuroplasticity is disruptcd in bipolar disordcr bcgins to makc scnsc.
curoplasticity may bc a ncccssary part of maintaining mood within a nor-
H P1S1LV1i M ,j
mal rangc, somchow "tuning thc rcsponsivcncss of our mood statc to cx-
pcricnccs and cnvironmcnt, allowing us to rcact to and thcn rccovcr hom
Thcrc is strong cvidcncc that chronic strcss impairs ncuroplasticity. This
last hnding is cxtrcmcly intcrcsting bccausc it may cxplain why strcss trig-
gcrs mood cpisodcs in pcrsons with mood disordcrs. [Much morc on strcss
and bipolar disordcr is to comc in chaptcr I8. )
Takcn togcthcr, thcsc hndings on thc importancc of ccll plasticity and
growth cxplain why mcdications that hclp with symptoms of bipolar dis-
ordcr, cspccially bipolar dcprcssion, takc scvcral wccks to do so.'
It may bc a whilc bcfrc wc undcrstand how all thc molccular and ccl-
lular picccs of this complicatcd story ht togcthcr, but thc work to unravcl thc
basic causc [or causcs) of bipolar disordcr is procccding vcry rapidly. And
whcn wc undcrstand cxactly what is "brokcn in bipolar disordcr, thc job of
hxing it will bccomc much casicr.
, M VAi
L M A 1 H
and antidcprcssant chccts. Pcrhaps an cvcn morc important chcct of this
class of mcdications is thcir ability to dccrcasc thc hcgucncy and scvcrity of
cpisodcs of thc illncss. Thus, thc vast majority of paticnts with bipolar dis-
ordcr arc trcatcd with onc or anothcr of thcsc mcdications, and somctimcs
with scvcral.
Wc'vc alrcady lcarncd about [ohn Cadc's discovcry in thc I(os of thc
thcrapcutic chccts of lithium in bipolar disordcr. 5ut lithium has an cvcn
oldcr history as a pharmaccutical, and it is just as intcrcsting as thc story of
Or. Cadc and his guinca pigs. In thc sccond ccntury AO, thc Crcck physician
Scranus Lphisios rccommcndcd that physicians who trcatcd paticnts suhcr-
ing hom mania should prcscribc "natural watcrs, such as hom] alkalinc
springs.' ' Wc now know that thc watcr hom many alkalinc springs is rich
in lithium. Roman physicians rccommcndcd that thcir paticnts "takc thc
watcrs at various springs fr various physical and mcntal ailmcnts. Oown
through thc ccnturics, ccntcrs fr hcaling grcw up around natural springs
all ovcr Luropc, hom thc littlc town in castcrn 5clgium callcd Spa to 5ath
in Lngland, Wicsbadcn in Ccrmany, and dozcns of othcr towns in Italy and
Crcccc. As thc scicncc of analytic chcmistry dcvclopcd, curious chcmists
and physicians cvaluatcd thcsc various springs and fund that thc watcrs of
many wcrc rich in lithium.
In thc middlc of thc ninctccnth ccntury, lithium compounds wcrc tricd
as trcatmcnts fr gout and kidncy stoncs. Cout is a painml arthritic con-
dition causcd by abnormally high lcvcls of uric acid in thc body, thc uric
acid is dcpositcd in thc frm of uratc crystals in thc j oints and othcr tis-
sucs. Kidncy stoncs arc also usually madc up of uratc compounds. It was
hopcd that lithium would somchow dissolvc thc uratc crystals in thc j oints
of gout paticnts and also dissolvc uratc kidncy stoncs. [Rcmcmbcr that Or.
Cadc pickcd lithium uratc to work with bccausc it is thc most solublc of thc
uratc compounds. ) Lnfrtunatcly, lithium did not turn out to bc hclpml fr
thcsc problcms, and thc approach was abandoncd. 5ut this work lcd to thc
frmulation of pharmaccutical prcparations of lithium compounds and to
infrmation on thc rangc of safc doscs fr lithium prcparations in humans.
In thc latc I(os, lithium camc to mcdical attcntion again whcn lithium
chloridc was introduccd as a salt substitutc fr paticnts with mcdical prob-
lcms such as hcart discasc and high blood prcssurc that rcguircd thcm to bc
on a low- sodium dict. 5ut whcn hcart paticnts wcrc givcn saltshakcrs mll of
lithium salts to sprinklc on thcir fod, thc rcsults wcrc catastrophic fr somc.
5ccausc lithium is toxic in surprisingly low conccntrations, substituting
lithium chloridc fr sodium chloridc turncd out to bc a disastcr. Thcrc wcrc
many rcports of scvcrc lithium poisoning and cvcn scvcral dcaths among
thcsc paticnts. Thc usc of lithium as a salt substitutc cndcd. This cpisodc had
thc chcct of giving lithium a vcry bad rcputation among physicians, and it
may havc bccn anothcr rcason fr thc dclay in acccpting Cadc's discovcry of
lithium as a trcatmcnt fr bipolar disordcr.
In thc Iyos, thc Oanish psychiatrist Morgans Schou bcgan what turncd
out to bc his lifc work. thc dcvclopmcnt and rchncmcnt of thc thcrapcutic
usc of lithium fr thc trcatmcnt of bipolar disordcr. Schou vcry guickly bc-
camc convinccd of thc chcctivcncss of lithium in trcating acutc mania, and
hc was onc of thc hrst clinical rcscarchcrs to bccomc convinccd of anothcr
thcrapcutic chcct of thc drug. its ability to prcvcnt mrthcr cpisodcs of illncss
[lithium`s prcvcntivc or rcby|ac||c chcct) . Schou had a hardcr timc con-
vincing his collcagucs around thc world that lithium could prcvcnt rccur-
rcnccs of bipolar disordcr, that paticnts should takc it cvcn ahcr thcir acutc
symptoms had subsidcd. In I6; Schou and his collcaguc Paul Christian
5aalstrup rcportcd on cighty-cight paticnts who had takcn lithium fr scv-
cral ycars and who had a dramatic rcduction in thc hcgucncy and duration
of thcir mood cpisodcs [hgurc 6- I shows a samplc of thcir rcsults) . Scvcral
paticnts who had bccn sick fr scvcral wccks out of cvcry ycar cxpcricnccd
a complctc rcmission of thcir illncss that lastcd morc than hvc ycars, thcir
illncss had csscntially ccascd. '
, M VAi
1 90 1 91 1 9Z 1 93 1 94 1 9
B l


|SS| D0

M80| 8
L|l0| U0 800| 0|Sl|8l|D0
licuar- i This graph illustratcs data hom six paticnts in 5aalstrup and
Schou`s carly study on thc prophylactic cdccts of lithium on bipolar symptoms.
Lach horizontal linc rcprcscnts thc symptom coursc of onc paticnt. In all thcsc
paticnts, whcn lithium was startcd, cpisodcs of mania and dcprcssion stoppcd
Scurce Oata hom IauI baaIstrup and Morgans Schou, "Lthum as a IrophyIactc Agcnt. !ts
Lhcct aganst Kccurrcnt Ocprcssons and Manc-Ocprcssvc Isychoss, Arch|ves c) Cenem|
Ps)ch|a|r) 6, no. z 6;). 6z-;z.
As thcy trcatcd morc and morc paticnts with thc mcdication, it bccamc
so apparcnt to Schou and his collcagucs that lithium fvorably altcrcd thc
coursc of bipolar illncss that thcy had cthical gualms about doing a morc
rigorous placcbo- controllcd study-onc in which bipolar paticnts would bc
dividcd into two groups, somc to rcccivc lithium and thc othcrs a placcbo.
I n a rathcr cranky I68 articlc titlcd "Prophylactic Lithium. Anothcr Thcra-
pcutic Myth scvcral 5ritish psychiatrists scoldcd thc Oancs fr rcporting
thcir rcsults without a placcbo group. ' So 5aalstrup and Schou did a lithium
discontinuation study in which thcy took paticnts who had bccn stablc on
lithium fr at lcast a ycar, dividcd thcm into two roughly cgual groups, and
in onc group substitutcd a placcbo fr thc lithium.
This was a dcu||c-|||nds|udy, thc most powcrml typc of clinical trial
possiblc-and now a rcguircd tcst fr ncw mcdications. In this typc of study,
paticnts who arc similar as to agc, diagnosis, scvcrity of illncss, and so frth
and who agrcc to bc in thc study arc dividcd into two groups. nc group
gcts thc mcdication that is bcing tcstcd, and thc othcr group [thc ccn|rc|
group) gcts a placcbo [or in somc studics thc control group rcccivcs a stan-
dard mcdication fr thc disordcr bcing studicd). Thc paticnts do not know
ALL1~S111Z1iL A11L1LiS M ,
whcthcr thcy arc taking thc ncw mcdication or thc placcbo, and ncithcr do
thc clinicians who cxaminc thcm fr improvcmcnt, hcncc thc tcrm dcu||c-
blind. It is only ahcr thc trial is ovcr that thc group mcmbcrship of thc pa-
ticnts is rcvcalcd and thc rcsults of thc two groups comparcd. Improvcmcnt
is mcasurcd obj cctivcly by using chccklists of symptoms and various rating
scvcrity scalcs that havc bccn vcrihcd as bcing rcliablc and valid.
Thc rcsults of thc 5aalstrup and Schou study wcrc dramatic. of thc thirty-
ninc paticnts whosc lithium was rcplaccd with thc placcbo, twcnty- onc rc-
lapscd within hvc months, of thc frty- hvc othcr paticnts, thosc whosc lith-
ium was not rcplaccd, ncnc had a rclapsc. In I;o 5aalstrup and Schou
publishcd thcir rcsults in thc samc 5ritish j ournal in which thcir critics'
papcr had appcarcd, cstablishing oncc and fr all that lithium`s prophylactic
chcct on bipolar disordcr was no myth.'
It has now bccn shown in many morc studics that lithium is not only
chcctivc in thc trcatmcnt of mania and dcprcssion, it also rcduccs thc sc-
vcrity, duration, and hcgucncy of manic and dcprcssivc cpisodcs of bipolar
Lithium is a naturally occurring clcmcnt fund in mincral springs, sca-
watcr, and ccrtain orcs. Likc its closc cousin sodium, it is ncvcr fund in its
purc frm in naturc but only combincd with othcr ions as a salt of onc typc
or anothcr. It is mincd on an industrial scalc fr usc in thc manufcturc
of ccramics and battcrics. Thcrapcutic lithium prcparations usually contain
lithium carbonatc [thc carbonatc ion combincd with lithium, whcn thc car-
bonatc ion is combincd with thc closcly rclatcd sodium, it frms sodium
carbonatc, which is common baking soda) .
5ccausc it is an clcmcnt, lithium is not chcmically transfrmcd [mctab-
olizcd) within thc body, and bccausc lithium atoms arc so similar to sodium
atoms, thc body handlcs lithium in much thc samc way it handlcs sodium.
Lithium is rapidly absorbcd through thc gastrointcstinal tract, cntcrs thc
bloodstrcam, and is climinatcd hom thc body by bcing hltcrcd out by thc
kidncys. [Tablc 6- I summarizcs thc thcrapcutic prohlc. )
Ocscriptions of thc chccts of a pharmaccutical in thc body always in-
cludc onc vital statistic. thc mcdication`s baq|{c. This is a mcasurc of how
guickly thc body gcts rid of thc pharmaccutical. Spccihcally, it is thc timc
rcguircd fr half thc amount of thc drug to bc climinatcd or mctabolizcd by
thc body. Put anothcr way, it is thc timc it takcs fr thc body to rcducc thc
lcvcl of thc mcdication by half. Thc half- lifc of lithium in adults is bctwccn
furtccn and thirty hours. ` Anothcr uscml numbcr that can bc dcrivcd hom
thc half-lifc statistic fr any mcdication is thc timc it takcs fr thc lcvcl of
mcdication to build up to a constant lcvcl in thc body, or in othcr words thc
0 M VAi
Tzeir- I Thcrapcutic pronlc of lithium
Medication class.
Brand names.
Other considerations.
Mood stabilizer
Eskalith, Eskalith CR, Lithobid, Lithonate, Lithotabs
:-o hours
Blood levels exremely important
timc it takcs fr thc amount bcing takcn in to cgual thc amount bcing clim-
inatcd. thc cqu||||r|umc| n|. 5y a scrics of mathcmatical stcps that wc don't
nccd to dctail hcrc, it can bc shown that thc cguilibrium point is always thc
samc fr all mcdications. hvc half-livcs. This mcans that sincc thc half-lifc
of lithium is roughly onc day, it will takc roughly hvc days fr a paticnt who
starts on lithium to rcach a stcady lcvcl of lithium in thc bloodstrcam. It also
mcans that if thc lithium dosc is changcd, it will takc about hvc days fr thc
blood lcvcl to stabilizc at thc ncw lcvcl.
5ccausc of thc toxicity and cvcn dcaths that wcrc rcportcd whcn hcart
paticnts sprinklcd it hccly on thcir fod as a salt substitutc, thcrc was a sig-
nihcant dclay in thc acccptancc of lithium as a thcrapcutic agcnt. Lithium
is a powcrml pharmaccutical, onc that must bc trcatcd with rcspcct. It has a
vcry low |bcracu||c |ndcx, mcaning that thc dihcrcncc bctwccn thc thcra-
pcutic dosc and a toxic dosc is small. " Iortunatcly, lithium can bc mcasurcd
in thc bloodstrcam accuratcly and chcaply, and thc dosagc can bc adjustcd
according to thc rcsults.
It is important to pay attcntion to lithium blood lcvcls not only to prc-
vcnt toxicity but also bccausc it has bccn clcarly dcmonstratcd in clinical
studics that lithium nccds to bc prcscnt in thc bloodstrcam at a ccrtain lcvcl
to bc chcctivc in most paticnts. [Wc spcak of a "thcrapcutic lcvcl in dis-
cussing thc chcctivc rangc of lithium in thc bloodstrcam fr trcatmcnt, not
a "normal lcvcl' Lithium is a tracc clcmcnt in thc body, normally prcscnt in
undctcctablc conccntrations. 5ipolar disordcr is not a lithium dchcicncy| )
[ust what that lcvcl should bc has bccn a mattcr of dcbatc, and thc dchnition
has shihcd ovcr thc ycars. 5ut an important study hom Massachusctts Ccn-
cral Hospital fund that a lcvcl of bctwccn o. 8 and I. o mcg/L [this stands
fr millicguivalcnts pcr litcr and is a chcmical mcasurc of conccntration)
was most chcctivc. In this doublc-blind study, bipolar paticnts wcrc di-
vidcd into two groups, a "standard- dosc group, whosc lithium lcvcls wcrc
kcpt bctwccn o. 8 and I. o mcg/L, and a "low- dosc group, whosc lcvcls wcrc
maintaincd bctwccn O. qand o. 6 mcg/L. Thc rcscarchcrs fund that thc rc-
lapsc ratc in thc "low- dosc group was morc than doublc that in thc "stan-
dard-dosc group [tablc 6- z) .
ALL1~S111Z1iL A11L1LiS M 1
Tzeir- z Comparison of highcr and lowcr lithium lcvcls in rclapsc ratcs of
bipolar disordcr
1rca|mcn| Any Man/c/ {cm
yrcu rc|asc Dcrcsscd m/xcd Hycman/c s|udy
Standard rangc :z) ) ) o z| :)
o. -:. o meq/L)
Low rangc z: ||) : z) :; ) ) :: z)
o. |-o. meq/L)
Scurce Oata hom Alan Gclcnbcrg, [ohn Kanc, Martn Kcllcr, IhIlp Lavor, [crroId Koscn-
baum, KaryI Colc, and [anct Lavcllc, "Comparson oI Standard and Low Lcvcls oI Lthum
r Mantcnancc 1rcatmcnt oI bpoIar Osordcr, New Eny|and ]curna| c) Med|c|ne zt, no. zz
(t8). t|8-.
Tcrc's morc to thcsc data than may initially mcct thc cyc, howcvcr.
Many morc paticnts hom thc "standard- dosc group than hom thc "low-
dosc group droppcd out of thc study bccausc of sidc chccts. Tc takc- homc
mcssagc sccms to bc that lcvcls closcr to I. o mcg/L arc morc protcctivc-but
that many pcoplc havc troublc taking that high a dosc bccausc of sidc chccts.
Many psychiatrists compromisc and try to maintain thcir paticnts at lcvcls
bctwccn thc "standard and thc "low rangc. Or. Schou, whom many con-
sidcr to bc thc fthcr of lithium thcrapy, rccommcndcd lcvcls of O. to o. 8
mcg/L. Howcvcr, it's vcry clcar that somc pcoplc havc good control of thcir
symptoms on cvcn lowcr lcvcls-cldcrly paticnts, fr cxamplc. Lithium lcv-
cls thus nccd to bc individualizcd to thc paticnt, and Or. Schou also points
out that "changcs in lithium lcvcls as small as O. I to o. z mcg/L] , upward or
downward, may substantially improvc paticnts' guality of lifc during main-
tcnancc trcatmcnt''
Tc lithium lcvcl in thc bloodstrcam riscs ahcr cvcry dosc, pcaks in
about two hours, thcn bcgins to fll again. If a paticnt takcs his lithium two
or thrcc timcs a day, thcrc will bc scvcral pcaks and vallcys. 5ccausc thc lcvcl
is rising and flling throughout thc day, it is important that thc blood fr a
lithium-lcvcl tcst bc drawn at a timc whcn it can bc corrcctly intcrprctcd.
Tc convcntion that has bccn adoptcd is to usc a twclvc-hour lcvcl, making
it convcnicnt to draw blood in thc mornings. Ior most paticnts this mcans
gctting to thc lab twclvc hours ahcr thcir bcdtimc dosc-fr cxamplc, by
II. OO a. m. if thc bcdtimc dosc was takcn at II. OOp. m. thc night bcfrc-with
thcir usual morning dosc in thcir pockct or pursc.
Lithium is unigucly chcctivc fr somc paticnts with bipolar disordcr,
fr whom it is truly a miraclc drug. In many of thcsc paticnts, othcr mcd-
ications simply don't control thcir symptoms as wcll. At thc consultation
2 M VAi
clinic at [ohns Hopkins, wc rcgularly scc paticnts who havc bccn told thcy
can no longcr takc lithium bccausc of mcdical issucs [usually bccausc thcy
havc dcvclopcd kidncy discasc, a complication of high blood prcssurc and
diabctcs as wcll as othcr mcdical disordcrs) . Many of thcsc paticnts havc
takcn lithium fr dccadcs with complctc control of thcir illncss. Somc havc
bccn so stablc that thcy havcn`t sccn a psychiatrist in ycars, gctting thcir
lithium trcatmcnt and monitoring hom thcir fmily doctor instcad. Thcsc
paticnts comc to us dcspcratc to start taking lithium again bccausc othcr
mcdications thcy'vc tricd sincc stopping lithium simply havcn`t kcpt thcm
wcll. Iortunatcly, most of thcm can rcsumc lithium trcatmcnt dcspitc thcir
kidncy discasc [thcrc havc cvcn bccn casc rcports of paticnts with such sc-
vcrc kidncy filurc that thcy rcguirc dialysis bcing safcly trcatcd with lith-
ium) . ' " Thcir dcspcration and thc grcat lcngths thcsc paticnts go to in ordcr
to gct back on lithium arc cxplaincd by its uniguc chcctivcncss fr thcm.
Lsually thcy arc paticnts with classic bipolar I disordcr, charactcrizcd by
scvcrc manias rcguiring hospitalization, ohcn with psychotic fcaturcs. An-
othcr illncss charactcristic is that thcir bctwccn- cpisodc rccovcry is usually
guitc complctc, that is, thcy do not havc smoldcring rcsidual mood symp-
toms fr long pcriods whcn thcy arc not acutcly ill. This group of paticnts,
fr whom lithium is fntastically chcctivc and fr whom nothing clsc works
guitc so wcll, has promptcd a numbcr of rcscarch proj ccts scarching fr gc-
nctic markcrs fr lithium`s thcrapcutic chcct. Thc hopc is that this rcscarch
will cvcntually lcad to a tcst that will hclp physicians sclcct mcdications fr
individual paticnts with mood disordcrs. In this casc, physicians want a tcst
that will prcdict whcthcr a particular paticnt is or is not likcly to bcncht
hom taking lithium.
Individuals vary widcly in thcir scnsitivity to thc sidc chccts of lithium
[and all othcr mcdications, fr that mattcr) . Somc paticnts will havc no sidc
chccts, othcrs will havc scvcral. Iortunatcly, almost all thc sidc chccts of
lithium can bc climinatcd or managcd [tablc 6- ) .
Many of lithium`s sidc chccts arc dcsc-rc|a|cd, mcaning that thc highcr
thc dosc, thc morc scvcrc thc sidc chcct. nc sidc- chcct managcmcnt strat-
cgy, thcn, is to lowcr thc lithium dosc. Thc advantagcs of highcr lcvcls arc
clcar, as notcd abovc, but most physicians will try to maintain paticnts at thc
lowcst dosc that controls thcir symptoms.
5ccausc of its similarity to sodium, lithium has somc of thc samc cf-
fccts that an incrcascd sodium [salt) intakc would havc. incrcascd thirst,
incrcascd urination, and watcr rctcntion. Thcsc sidc chccts arc ohcn tcm-
porary and subsidc as thc body adjusts to thc mcdication. Many paticnts
noticc this slight and tcmporary incrcasc in urination and thirst whcn thcy
ALL1~S111Z1iL A11L1LiS M j
Tzeir- Trcatablc sidc edects of lithium
S/dc c_cc|
Nausea, diarrhea
Take immediately a6er meals
Switch preparations
Weight gain Diet and exercise
Tirst, hequent urination Diuretics helpml, but must be prescribed
by an M.D. see text)
Tremor Beta-blocker medications
Flareup of preexisting dermatologic Dermatologic preparations
Hypothyroidism Tyroid medications
start taking lithium. Ior somc paticnts, howcvcr, it's ahcr taking lithium fr
many ycars that thcy noticc thcy nccd to urinatc much morc ohcn and hnd
that thcy arc hcgucntly thirsty. This occurs bccausc lithium can ahcct thc
mnctioning of thc kidncys ovcr timc. Rcmcmbcr that thc kidncys' job is to
rcmovc wastc products hom thc bloodstrcam, thcy hltcr ncarly twcnty gal-
lons of blood cvcry hour to do this, and thcy rccyclc ncarly all of this fluid
back into thc bloodstrcam. Whcn takcn fr many ycars, lithium can impair
this rccycling mnction, so that largc amounts of urinc arc produccd. Thc
tcrm fr this problcm is d|a|c|cs|ns||dus[which has nothing to do with di-
abctcs mcllitus, thc common "sugar diabctcs). This problcm dcvclops vcry
slowly, is casy to diagnosc with a fcw laboratory tcsts, and is trcatablc with
amiloridc, a drug that changcs how thc kidncy rcabsorbs watcr and othcr
agcnts. Whcn caught carly on, this problcm is usually complctcly rcvcrsiblc,
so it's vcry important that paticnts taking lithium lct thcir doctor know if
thcy hnd thcmsclvcs awaking morc ohcn to urinatc during thc night.
Whcn lithium was hrst bcing prcscribcd, conccrn arosc bascd on casc
rcports that lithium disruptcd thc kidncys' hltcring systcm, causing thc kind
of damagc that can rcsult in thc nccd fr dialysis . This has now bccn shown
to bc cxtrcmcly rarc, occurring almost cntircly in pcrsons who arc alrcady
at risk fr kidncy damagc hom othcr causcs, such as poorly controllcd high
blood prcssurc or diabctcs. Iortunatcly this problcm is also vcry slow to
dcvclop. ' '
5ccausc of thcsc potcntial problcms, blood tcsts that mcasurc kidncy
mnctioning arc routincly ordcrcd fr paticnts taking lithium, in addition to
blood tcsts to monitor thcir lithium blood lcvcls.
Lithium is irritating to thc gastrointcstinal tract and can causc nausca
or diarrhca. Taking it on a mll stomach can casc thcsc problcms considcr-
ably. A hnc shaking in thc hands [trcmor) can occur at highcr dosagc lcvcls.
q M VAi
Thcsc problcms can somctimcs bc allcviatcd with slow- rclcasc prcparations
of lithium, which rcducc thc pcak blood lcvcl that occurs ahcr cach dosc.
Mcdications uscd to trcat trcmors, callcd |c|a ||cc/crs, arc hcgucntly prc-
scribcd and can bc vcry hclpml. Wcight gain can bc an annoying sidc chcct
and unfrtunatcly has an cgually annoying rcmcdy. dict and cxcrcisc.
5ctwccn and , pcrccnt of paticnts trcatcd with lithium dcvclop dc-
prcsscd thyroid gland mnctioning [hypothyroidism) . ' ' Whcn hypothyroid-
ism dcvclops, it sccms to bc ablc to causc an incrcasc in mood cycling in
addition to thc symptoms of too littlc thyroid hormonc [low cncrgy, dry
skin, scnsitivity to hcat, and pumncss around thc cycs arc somc of thc carly
signs). If a pcrson's lithium sccms to "stop working-that is, if thc pcrson
suddcnly sccms to havc an accclcration in hcr illncss-hypothyroidism
should bc suspcctcd. Whcn it docs occur, hypothyroidism can bc trcatcd by
thyroid- rcplaccmcnt mcdications. A tcst of thyroid mnctioning is thc third
in thc battcry of blood tcsts routincly ordcrcd fr lithium paticnts .
Lithium can causc flarcups of prccxisting skin conditions but only rarcly
causcs ncw dcrmatological problcms. Paticnts with psoriasis, acnc, and othcr
such problcms may nccd closcr fllow- up hom thcir dcrmatologist.
Anothcr sidc chcct that troublcs a signihcant numbcr of paticnts taking
lithium is a noticcablc dulling of mcntal mnctioning and coordination. Pa-
ticnts complain that thcir ability to mcmorizc and lcarn is ahcctcd and that
thcy havc a dimcult- to- cxplain scnsc of mcntal sluggishncss. Ior ycars thcsc
complaints wcrc downplaycd by clinicians, many of whom tosscd thcm oh
as coming hom paticnts who simply wcrcn't uscd to fccling "normal,' who
misscd thc mcntal alacrity of hypomania. This vicw sccmcd to bc supportcd
by rcscarch using psychological tcsts on bipolar paticnts taking lithium, rc-
scarch that has bccn inconclusivc. 5ut whcn nonpaticnt voluntccrs wcrc
givcn lithium and similarly tcstcd, thcrc was a small but dchnitc drop- oh
i n thcir pcrfrmancc, proving that lithium- induccd mcntal sluggishncss i s a
vcry rcal problcm fr somc paticnts. ' ' This is a dosc-rclatcd sidc chcct and is
anothcr rcason to strivc fr thc lowcst possiblc maintcnancc dosc of lithium
that still controls mood symptoms adcguatcly.
Lithium has bccn associatcd with birth dcfccts, cspccially ccrtain hcart
dcfccts. At onc timc, it was rccommcndcd that womcn ncvcr gct prcgnant
whilc taking lithium, but morc rcccnt rcscarch has shown that whilc lithium
incrcascs thc risk of scrious hcart problcms in thc fctus, thc risk is still vcry
low. What to do about taking lithium during prcgnancy is a complicatcd
dccision that should bc discusscd wcll bcfrchand with your psychiatrist
and your obstctrician. [Scc chaptcr i fr a morc complctc discussion of
mcdications and prcgnancy.) Lithium is sccrctcd in brcast milk, so paticnts
taking lithium should not brcast-fccd.
ALL1~S111Z1iL A11L1LiS M j
Lamotrgnc [LamctaI]
Scvcral ycars ago, I was riding in a cab with a collcaguc of minc as wc rc-
turncd to our hotcls ahcr spcnding thc day at an intcrnational confcrcncc on
bipolar disordcr in Pittsburgh. Wc wcrc talking about thc scminars wc had
attcndcd that day, discussing how wc might bcttcr classify bipolar disordcrs,
whcthcr lithium is safc during prcgnancy, and othcr bipolar topics of that
day's scssions. Ouring a pausc in our convcrsation, thc cab drivcr lookcd
back at us in his rcarvicw mirror and askcd, "Oo cithcr of you guys prcscribc
Lamictal Wc wcrc both a bit surpriscd by thc gucstion, sincc lamotriginc
had not yct bccn approvcd by thc Iood and Orug Administration [IOA) to
trcat bipolar disordcr, but wc rcplicd that ycs, wc had prcscribcd thc ncw
drug fr scvcral of our paticnts at [ohns Hopkins . Thc cabbic pauscd fr a
short momcnt and thcn said, "That's good . . . . Ya know, Lamictal savcd my
Lamotriginc [brand namc Lamictal) is somcthing of a child prodigy
among mcdications uscd to trcat bipolar disordcr. Lnlikc othcr mcdications,
which bccamc common trcatmcnts fr bipolar disordcr only ahcr many ycars
of invcstigation and tcsting, lamotriginc provcd its valuc in trcating bipolar
disordcr vcry guickly. As a rcsult it wcnt hom an uncommonly uscd drug
prcscribcd mostly at rcscarch mcdical ccntcrs to a mainstay of thc trcatmcnt
of bipolar disordcr in only a fcw ycars . Likc scvcral othcr mcdications wc
will discuss, lamotriginc was introduccd as a mcdication to trcat scizurc dis-
ordcrs. Thc hrst studics on lamotriginc appcarcd in thc I8os, dcscribing it
as a uscml "add- on thcrapy fr cpilcpsy paticnts who wcrc alrcady taking
othcr antiscizurc mcdications. Ouring thc carly invcstigations of this usc,
rcscarchcrs notcd that paticnts who took lamotriginc fr scizurc control rc-
portcd an improvcmcnt in thcir mood and scnsc of wcll-bcing-cvcn if it
hadn't hclpcd much with thcir scizurcs. Thcsc obscrvations lcd to clinical
trials in paticnts with mood disordcrs, which guickly rcvcalcd that lamotrig-
inc is an chcctivc mcdication fr many such paticnts.
Lamotriginc has scvcral chccts on thc brain that might cxplain its cm-
cacy in bipolar disordcr. It inhibits thc rclcasc of thc ncurotransmittcr glu-
tamatc, an amino acid that causcs stimulation of various ncural circuits.
Clutamatc is also thc signal that thc ncrvous systcm uscs to triggcr a kind of
ccllular suicidc callcd ac|cs|s that inactivatcs and rcmovcs malmnction-
ing ncurons. Thcrc is cvidcncc that abnormally high lcvcls of glutamatc arc
prcscnt in scvcral brain arcas of pcrsons with bipolar disordcr, suggcsting
that lamotriginc's chcctivcncss is duc to a dialing back of glutamatc activity
in thc brain to morc normal lcvcls. ''
Thc most cxciting aspcct of lamotriginc's prohlc is its chcctivcncss in
bipolar dcprcssion. nc of thc hrst rcports on its usc in thc trcatmcnt of
bipolar disordcr told of a paticnt who had suhcrcd hom rapid- cycling bi-
polar I disordcr sincc hc was furtccn ycars old. '` In thc ycar bcfrc start-
ing lamotriginc, hc had bccn cithcr dcprcsscd or manic continuously, with
no pcriod of normal mood. Whcn thc rcscarch tcam hrst saw him, hc had
bccn scvcrcly dcprcsscd and had not rcspondcd to lithium, to othcr mood
stabilizcrs, or cvcn to antidcprcssants. Ahcr bcginning to takc lamotriginc,
his dcprcssivc symptoms gradually improvcd, and clcvcn months latcr hco
had no rccurrcncc of cithcr dcprcssivc or manic symptoms. Casc rcports
and studics of lamotriginc as a mcdication addcd to othcr agcnts startcd to
accumulatc and continucd to look promising.
In zootwo largc studics wcrc publishcd that comparcd thc cmcacy of
lamotriginc with lithium [and also with a placcbo) in kccping paticnts with
bipolar disordcr hom having anothcr mood cpisodc, cach study lastcd cigh-
tccn months. In onc study, thc paticnts wcrc rccovcring hom a manic or
mixcd cpisodc as thcy cntcrcd thc study, in thc othcr, paticnts wcrc rccovcr-
ing hom a dcprcssion. ' " In thc scction on lithium, I mcntioncd that thc bcst
way to tcll whcthcr a mcdication is truly chcctivc is to do a doublc-blind,
placcbo-controllcd study. 5oth of thcsc studics comparing lamotriginc with
lithium and a placcbo wcrc carricd out in just this way, thcy also wcrc largc
studics that includcd hundrcds of paticnts, and thcy lastcd fr a ycar and a
half-much longcr than most mcdication trials. So whcn both studics rc-
portcd that lamotriginc was just as chcctivc as lithium in kccping paticnts
wcll, this ncw mcdication suddcnly camc into thc spotlight and bccamc onc
of thc fundations of thc trcatmcnt of bipolar disordcr.
Thc cxciting hnding hom thcsc studics was that lamotriginc is cspccially
chcctivc against dcprcssion in bipolar disordcr-cxtrcmcly good ncws. This
was such an important hnding bccausc, as you will scc latcr, thc dcprcssion
of bipolar disordcr is much morc dimcult to trcat than manic or mixcd statcs
[scc "Trcating 5ipolar Ocprcssion`' in chaptcr ;). You may rcmcmbcr hom
chaptcr zthat individuals with bipolar II disordcr havc morc problcms with
dcprcssion than with mania and that thcsc dcprcssions can bc cspccially
long, dcbilitating, and dimcult to trcat. Lamotriginc can ohcn hll an import-
ant thcrapcutic nccd fr thcsc paticnts, bccausc fr thcm lithium is ohcn
lcss chcctivc.
Lamotriginc has a half- lifc of about twcnty- fur hours, and its mctab-
olism i s ahcctcd by taking carbamazcpinc and valproatc [tablc 6- () . 5lood-
lcvcl tcsts arc not routincly ordcrcd fr lamotriginc bccausc of its low toxic-
ALL1~S111Z1iL A11L1LiS M ,
Tzeir- | TerapeutiL pronlc of lamotriginc
Medication class.
Brand name.
Other considerations.
Mood stabilizer anticonvulsant)
:-z| hours
Anected by carbamazepine, valproate
Rarely causes severe skin rashes, but otherwise has
good side- enect pronle
ity and bccausc thcrapcutic chccts havc not bccn corrclatcd with particular
amounts in thc blood.
In contrast to thc othcr mood stabilizcrs, lamotriginc causcs only mini-
mal sidc chccts. Paticnts taking it may havc somc initial nausca or gastroin-
tcstinal upsct and thc sort of sidc chccts that many mcdications ahccting thc
brain can causc. slccpincss, light- hcadcdncss or dizzincss, and hcadachcs. At
highcr doscs, somc paticnts complain of conccntration problcms similar to
thosc ohcn rcportcd by paticnts taking lithium. In my cxpcricncc, lowcring
thc dosc usually takcs carc of this problcm.
A vcry rarc but vcry scrious problcm that has bccn associatcd with la-
motriginc is a dangcrous typc of allcrgic skin rash callcd |cx|c c|dcrma|
nccrcs|s TLD) . TLD is thc most cxtrcmc frm of a group of allcrgic skin
rcactions that arc lumpcd togcthcr undcr thc tcrm crythcma multiformc.
Thcsc problcms wcrc rcportcd right ahcr lamotriginc was introduccd as a
trcatmcnt fr cpilcpsy in thc carly Ios. Whcn rcscarch was donc to scc
which paticnts wcrc at highcst risk fr thcsc scrious rcactions, it was discov-
crcd that childrcn and paticnts who startcd thc drug at high doscs wcrc morc
likcly than othcrs to dcvclop a scrious rash. Subscgucntly, thc drug's man-
ufcturcr rccommcndcd against prcscribing lamotriginc to childrcn cxccpt
undcr spccial circumstanccs and also changcd thc dosing rccommcndations
fr starting thc drug in adults. ow paticnts start lamotriginc at a vcry low
dosc and gradually incrcasc it ovcr a pcriod of wccks. Although this mcans
that it may takc hvc wccks or morc to gct to thc usual thcrapcutic dosc of
zoo to (oo mg/day, thc risk of scrious skin rcactions to lamotriginc has vir-
tually bccn climinatcd. Sincc thcsc dosing rccommcndations wcrc put into
chcct, thc numbcr of paticnts dcvcloping scrious rashcs has droppcd to thc
numbcr in thc gcncral population. In thc pivotal clinical trials whcrc lam-
otriginc was prcscribcd to scvcral thousand paticnts fr thc trcatmcnt of
bipolar disordcr, nonc of thc paticnts dcvclopcd a scrious rash. '
cvcrthclcss, many individuals dcvclop minor skin rcactions to mcd-
Tzeir6- Te Stanford protocol fr paticnts starting lamotriginc
Do not start lamotrigine within z weeks of any rash, vral infection, vaccination
During nrst months of treatment, avoid new
Medicines, fods
Soaps, cosmetics, conditioners, deodorants
Detergents, mbric so6eners
During nrst months of treatment, avoid
Poison ivy/oak, sunburn
ications and lots of othcr things as wcll, so it's important whcn a pcrson
starts taking lamotriginc to takc prccautions against dcvcloping a rash hom
anothcr sourcc. If a rash dcvclops in a paticnt taking lamotriginc, it prcscnts
somcthing of a thcrapcutic dilcmma. Is thc paticnt's rash crythcma multi-
frmc or a minor skin rcaction If thc rash is a scrious onc, is lamotrig-
inc thc culprit Thc paticnt might bc told to stop thc drug unncccssarily,
pcrhaps missing out on a mcdication that might bc vcry chcctivc. Ior this
rcason, paticnts starting on lamotriginc should considcr thc protocol dcvcl-
opcd at Stanfrd Lnivcrsity to prcvcnt skin rashcs hom othcr sourccs [ tablc
6-y ) . I had onc paticnt who had bccn told by hcr prcvious psychiatrist to stop
lamotriginc, which up to that point had sccmcd vcry hclpml fr hcr bipolar
dcprcssion, bccausc shc had dcvclopcd what in rctrospcct was probably a
rcaction to poison ivy. Shc was ablc to rcstart lamotriginc and movc up to
a thcrapcutic dosc with no problcms. I tcll my paticnts as I hand thcm thc
prcscription, "o gardcning, no hiking, no ncw rcstaurants or shampoos or
clothcs dctcrgcnts, stay out of thc sun and takc carc of your skin|
A corollary t o thc start- low protocol fr lamotriginc i s that a pcrson
who stops taking it fr a pcriod of timc should not rcsumc taking it at thc
samc dosc. Lxpcrts rccommcnd that paticnts who arc oh lamotriginc fr
onc wcck or morc should rcstart thc drug at thc low bcginning dosc.
VaIproatc [cpakotc, cpakcnc, EpvaI]
Thc dcvclopmcnt of valproatc [brand namcs includc Ocpakotc and Oc-
pakcnc) fr thc trcatmcnt of bipolar disordcr is anothcr convolutcd study in
scrcndipity. Valproic acid is a carbon compound similar to othcrs that arc
fund in animal fts and vcgctablc oils. it is a ftty acid. It was hrst synthc-
sizcd in I88z and was uscd fr many ycars as an organic solvcnt fr a vari-
cty of purposcs. [Rcmcmbcr that a solvcnt is a liguid that othcr substanccs
casily dissolvc into. ) Many dccadcs ago pharmacists uscd it as a solvcnt fr
bismuth salts, which wcrc uscd to trcat stomach and skin disordcrs.
In thc carly I6os, scicntists looking fr trcatmcnts fr cpilcpsy wcrc
ALL1~S111Z1iL A11L1LiS M
working with a group of ncw pharmaccutical compounds that appcarcd
promising but wcrc dimcult to dissolvc. [Is this bcginning to sound f-
miliar) Thcy discovcrcd that valproic acid was an chcctivc solvcnt fr thc
compounds thcy wcrc tcsting, and thcy startcd using it to dissolvc thcir tcst
drugs fr animal cxpcrimcntation. As thcy tcstcd various ncw pharmaccu-
ticals, thc rcsults thcy obtaincd sccmcd to bc conmsing-until somconc rc-
alizcd that it didn`t mattcr wb|cb of thc ncw pharmaccuticals was uscd. As
long as anyof thcm was dissolvcd in valproic acid, thc drug was fund to bc
chcctivc i n stopping cpilcptic scizurc activity. It s oon bccamc obvious that it
was thc valproic acid that was stopping thc scizurcs, not what was dissolvcd
in it. 5y I;8 valproatc had bccn approvcd by thc Iood and Orug Adminis-
tration fr usc in trcating cpilcpsy. '
In thc I6os thcrc wcrc somc rcports that valproatc might bc hclpml in
trcating mood disordcrs, and throughout thc latc I6os and carly I;os, a
Ircnch psychiatrist namcd Lambcrt publishcd a scrics of papcrs about using
it to trcat bipolar disordcrs. Ahcr thc discovcry that anothcr anti-cpilcpsy
mcdication, carbamazcpinc, was chcctivc in trcating mania [scc thc ncxt
scction of this chaptcr), intcrcst in thc possibilitics of valproatc as a mood
stabilizcr grcw. I n thc mid-I8os, thcrc wcrc scvcral studics by Amcrican
psychiatrists of thc usc of valproatc in trcating bipolar disordcr, and tcn
ycars latcr valproatc had bccomc hrmly cstablishcd as an chcctivc antimanic
mcdication and a mood stabilizcr.
Valproatc's thcrapcutic action in bipolar disordcr-or in cpilcpsy, fr
that mattcr-is still unknown. It is known to improvc ncuronal transmission
in thc brain that is mcdiatcd by thc ncurotransmittcr gamma aminobutyric
acid [CA5A) . CA5A sccms to havc an inhibitory or modulating chcct on
many brain circuits, and valproatc's chcct may bc to cnhancc this modulator
in somc way.
Thc half-lifc of valproatc is bctwccn six and sixtccn hours in adults
[tablc 6- 6) . Thus, it rcachcs cguilibrium in thc body morc guickly than lith-
ium, in two to thrcc days. Valproatc sccms to havc somc advantagcs ovcr
lithium in thc trcatmcnt of acutc manic cpisodcs. Iirst, it appcars to work
morc guickly. Whcrcas lithium may takc up to thrcc wccks to havc its mll
chcct, valproatc has bccn shown to start working within hvc days. Sccond,
valproatc also sccms to bc morc chcctivc than lithium fr ccrtain subgroups
of manic paticnts. paticnts with rapid cycling [fur or morc mood cpisodcs
pcr ycar) and paticnts with mixcd mania [a mixturc of manic hypcractivity
and prcssurcd thinking with dcprcsscd or unplcasant mood) . ' ' Third, val-
proatc is much lcss toxic than lithium.
Controllcd studics of thc usc of val pro atc to trcat acutc dcprcssion and
0 M VAi
Tzeir - Tcrapcutic pronlc of valproatc
Medication class.
Brand names.
Other considerations.
Mood stabilizer anticonvulsant)
Depakene, Depakote, Epival
-: hours
Anected by other antiepilepsy drugs
Blood-level tests helpml, blood tests fr liver
inammation are needed
to prcvcnt rccurrcnccs of bipolar disordcr havc bccn lcss imprcssivc. '" In
fct, if onc sticks to thc morc rigorous controllcd studics, it can bc said that
valproatc should bc uscd only to trcat acutc mania and that thc lack of strong
cvidcncc fr its bcncht in dcprcssion or fr maintcnancc trcatmcnt argucs
against any othcr usc in bipolar disordcr. '' cvcrthclcss, any psychiatrist
with cxpcricncc in trcating mood- disordcr paticnts will tcll you that somc
paticnts nccd and bcncht hom valproatc and that fr thcm it is cxtrcmcly
and somctimcs unigucly chcctivc. It may bc that thcsc paticnts havc an un-
usual variant of bipolar disordcr and that thc bcncht of valproatc fr thcsc
paticnts gcts lost in largc studics, whcrc thcy arc vastly outnumbcrcd by pa-
ticnts who do not rcspond to valproatc.
Likc lithium, valproatc can bc mcasurcd in thc bloodstrcam, blood lcvcls
abovc (y mcg/ml [micrograms pcr millilitcr) havc bccn shown to bc ncccs-
sary fr thc thcrapcutic chcct to occur, and sidc chccts bccomc morc prob-
lcmatic at lcvcls grcatcr than Izy mcg/ml. '' Scvcral studics show that val-
proatc is hclpml in cyclothymia, bipolar II, and "soh bipolar disordcrs and
that lowcr doscs and lowcr blood lcvcls arc rcguircd than in thc trcatmcnt
of bipolar I. '' As with lithium, blood fr a tcst of valproatc lcvcls should bc
drawn twclvc hours ahcr thc last dosc of mcdication.
Sidc chccts that arc common as a paticnt starts taking valproatc includc
stomach upsct and somc slccpincss. Thcsc problcms usually go away guickly.
Incrcascd appctitc and wcight gain arc pcrhaps thc most scrious sidc chccts.
Mild trcmor occurs as wcll and can bc trcatcd with bcta-blockcr mcdication.
A fcw paticnts rcport hair loss, usually tcmporary, which rcsolvcs cvcn morc
guickly with thc usc of shampoos and vitamin prcparations containing thc
mincrals zinc and sclcnium. ''
Scvcral cascs of scvcrc livcr problcms havc bccn rcportcd in paticnts
taking valproatc, but thcsc havc occurrcd almost cxclusivcly in childrcn tak-
ing thc drug fr control of cpilcpsy, most of whom had othcr mcdical prob-
lcms and wcrc taking scvcral dihcrcnt mcdications. A I8 rcvicw articlc
ALL1~S111Z1iL A11L1LiS M 1
statcs that no ftalitics hom livcr problcms causcd by valproatc had cvcr
bccn rcportcd in paticnts ovcr thc agc of tcn who wcrc taking only val pro atc.
[ust to bc on thc safc sidc, howcvcr, paticnts taking valproatc fr thc hrst
timc arc givcn a blood tcst that can dctcct livcr inflammation and thc tcst is
rcpcatcd at appropriatc intcrvals whilc thcy arc taking it. Sincc valproatc can
also, in rarc cascs, causc a drop in blood counts, a complctc blood count is
usually donc as wcll. Thcsc arc vcry rarc problcms, and cvcn whcn thcy do
occur, thcy dcvclop slowly and usually during thc hrst sb months of thcrapy.
Thus, thcy can bc dctcctcd with routinc blood tcsts. cvcrthclcss, paticnts
on valproatc should bc on thc lookout fr signs oflivcr or blood- count prob-
lcms, which includc unusual blccding and bruising, j aundicc [ycllowing of
thc cycs and skin) , fcvcr, and watcr rctcntion.
Valproatc has bccn associatcd with birth dcfccts, and womcn of child-
bcaring agc should practicc birth control whilc taking valproatc if thcrc is
any possibility of bccoming prcgnant.
Carhamazcpnc [TcgrctoI, Equctro, EptoI]
Ahcr thc introduction of carbamazcpinc fr thc control of cpilcpsy in
thc I6os, scvcral rcports appcarcd indicating that cpilcpsy paticnts taking
carbamazcpinc who also had mood problcms not only had good control of
thcir scizurcs but had improvcmcnt in thcir psychiatric symptoms as wcll. It
was a small stcp to tcst carbamazcpinc in paticnts with mood problcms who
did not havc cpilcpsy. Much of thc carly work on thc usc of carbamazcpinc
in bipolar disordcr was donc by [apancsc clinicians looking fr an altcrna-
tivc to lithium, which was not approvcd fr usc in [apan until ycars ahcr it
was availablc in thc Lnitcd Statcs. In I8o a study appcarcd in thc Amcr|can
)curna|c}Psycb|a|ry titlcd "Carbamazcpinc in Manic- Ocprcssivc Illncss. A
cw Trcatmcnt,' and thc racc was on to rchnc thc usc of this mcdication
in bipolar disordcr and to dchnc thc group or groups of paticnts whom it
hclpcd thc most. '`
Although carbamazcpinc has bccn uscd to trcat bipolar disordcr fr scv-
cral dccadcs, lcss rcscarch has bccn donc on its cmcacy in this illncss than
fr othcr mcdications. This gap is slowly bcing hllcd, howcvcr, and ncwcr
studics havc appcarcd, promptcd by thc dcvclopmcnt of a sustaincd- rclcasc
prcparation of carbamazcpinc.
Lvcry oncc in a whilc a paticnt of minc rcgucsts that I prcscribc thc
"bcst mood stabilizcr or antidcprcssant mcdication thcrc is. I usually rc-
spond by saying that if thcrc wcrc a "bcst mcdication in a particular class
of mcdications, it would bc thc only pharmaccutical manufcturcd and prc-
2 M VAi
scribcd. What would bc thc point of using anything clsc Thc rcason thcrc
arc so many drugs of a particular typc is that somc work bcttcr or havc fcwcr
sidc chccts in particular paticnts. Many ncwcr mcdications don't sccm to bc
morc chcctivc than availablc oncs whcn studicd in largc groups of paticnts,
but thcy arc clcarly bcttcr fr ccrtain paticnts who can`t takc or don`t rcspond
to an oldcr agcnt.
Carbamazcpinc is onc such mcdication. it docsn`t sccm to havc any big
advantagc in most studics of groups of paticnts, but it works vcry wcll-
in fct, works whcn othcr mcdications do not-fr somc paticnts . In onc
wcll- dcsigncd doublc-blind study, manic paticnts who took carbamazcpinc
actually sccmcd to do worsc than paticnts taking lithium. '" 5ut most psychi-
atrists havc had a paticnt likc "Ms. 5. ,' whosc casc history was rcportcd in a
papcr hom thc ational Institutc of Mcntal Hcalth [IMH) in I8 .
Ms. 5. , a y-ycar- old woman, had a history of trcatmcnt rcsistant, rapid
cycling manic- dcprcssivc illncss that rcguircd continuous statc hospi-
talization hom Iy6 to hcr admission to IMH in I;8. Shc had bccn
non-rcsponsivc to antipsychotic mcdications, tricyclic antidcprcs-
sants] and lithium . . . . Ahcr institution of carbamazcpinc, both mood
phascs improvcd dramatically and shc was ablc t o bc dischargcd . . . .
Ouring a subscgucnt hospitalization hcr scvcrc mania again did not
rcspond to antipsychotic mcdications] and shc was not ablc to lcavc
thc hospital until shc was trcatcd with carbamazcpinc. '
In this study thc authors notcd that "additional improvcmcnt appcarcd to
occur whcn antipsychotic mcdications] wcrc uscd in conjunction with car-
bamazcpinc or whcn lithium and carbamazcpinc wcrc uscd in combina-
tion'' This had bccomc carbamazcpinc's nichc. a sccond-linc mood- stabil-
izing agcnt fr paticnts who do not rcspond to othcr agcnts, it was ohcn uscd
in combination with othcr agcnts. Howcvcr, at lcast onc placcbo- controllcd
study using carbamazcpinc alonc to trcat paticnts hospitalizcd with mania
supportcd thc idca that this mcdication may bc undcruscd and can bc hclp-
ml fr many paticnts. ''
Likc thc othcr mood- stabilizing mcdications, carbamazcpinc can bc mca-
surcd in thc bloodstrcam, and blood-lcvcl tcsts can bc uscd to adjust thc
dosc. Lnfrtunatcly, not much work has bccn donc on carbamazcpinc blood
lcvcls i n bipolar paticnts, so thc thcrapcutic rangc uscd fr thc trcatmcnt of
cpilcpsy i s usually thc targct that psychiatrists aim fr i n thcir paticnts.
Carbamazcpinc is mctabolizcd in thc livcr [tablc 6-;), and likc somc
othcr drugs, it causcs thc livcr to incrcasc thc lcvcl of thc cnzymcs that mc-
tabolizc it. This mcans that thc longcr a pcrson takcs carbamazcpinc, thc
morc guickly thc livcr gcts rid of it. So ahcr a fcw wccks, thc blood lcvcls
may go down and thc dosc may nccd to bc incrcascd. This incrcasc in livcr
ALL1~S111Z1iL A11L1LiS M j
Tnsir - ; Tcrapcutic pronlc of carbamaZepine
Medication class.
Brand names.
Other considerations.
Mood stabilizer anticonvulsant)
Tegretol, Equetro, Epitol
:-: hours shortens over time)
Complex, anects and is anected by other drugs
Blood-level tests helpml, blood tests fr liver
inammation and blood abnormalities needed
cnzymcs can also ahcct othcr mcdications that thc paticnt might bc tak-
ing, including ccrtain tranguilizcrs, ccrtain antidcprcssants, othcr cpilcpsy
mcdications, and somc hormoncs. Thc changc in hormonal lcvcls is vcry
important fr womcn using birth control, sincc somc oral contraccptivcs
that usc vcry low hormonc lcvcls losc thcir chcctivcncss if takcn with car-
bamazcpinc. It is vcry important that all physicians involvcd in a pcrson's
carc know whcn thc pcrson has startcd taking carbamazcpinc so that dosagc
adjustmcnts fr othcr mcdications can bc madc.
Carbamazcpinc can causc thc samc sort of gcncral sidc chccts as many
othcr mcdications that ahcct thc brain. slccpincss, lighthcadcdncss, and
somc initial nausca. Thcsc problcms tcnd to bc short- livcd and dosc-rclatcd.
As with valproatc, thcrc havc bccn rarc cascs of livcr problcms associ-
atcd with carbamazcpinc, so blood tcsts fr livcr inflammation arc routincly
donc. Thcrc havc bccn cvcn rarcr rcports of dangcrous changcs in blood
counts, so blood ccll counts arc also donc, cspccially i n thc hrst scvcral
wccks of thcrapy. Cascs of a dangcrous skin rcaction callcd Stcvcns- [ohnson
syndromc havc bccn attributcd to carbamazcpinc, this is anothcr of thc sc-
vcrc variants of crythcma multifrmc that I mcntioncd in thc discussion of
lamotriginc. All thcsc problcms arc guitc rarc, but paticnts should bc on thc
watch fr thc dcvclopmcnt of a rash, j aundicc, watcr rctcntion, blccding or
bruising, or signs of infcction.
Oxcarhazcpnc [TrIcpta]
As its namc suggcsts, oxcarbazcpinc [brand namc Trilcptal) is vcry sim-
ilar to carbamazcpinc. It is anothcr mcdication uscd to trcat cpilcpsy, and it
sccms to work similarly to carbamazcpinc but has scvcral advantagcs ovcr it.
xcarbazcpinc is not associatcd with thc blood-count problcms that can bc
causcd by carbamazcpinc or with thc changcs i n livcr cnzymcs that ahcct thc
mctabolism of othcr drugs. This makcs it signihcantly casicr to takc, with lcss
q M VAi
nccd fr monitoring blood tcsts and changcs in dosagc. It also appcars lcss
likcly to causc Stcvcns- [ohnson syndromc. Much of thc carly work on oxcar-
bazcpinc in bipolar disordcr was donc in Luropc, and studics by Ccrman in-
vcstigators in thc mid-I8os suggcstcd it was as bcnchcial as carbamazcpinc
in trcating mania. Morc rcccntly, Amcrican clinicians havc also publishcd
fvorablc rcports on its safcty and cmcacy, cspccially as an "add- on`' to othcr
mood stabilizcrs, and thc chcctivcncss of oxcarbazcpinc fr brcakthrough
manic symptoms has bccn cspccially wcll cstablishcd. '"
Many clinicians havc bccn rcluctant to prcscribc oxcarbazcpinc's parcnt
compound, carbamazcpinc, bccausc of thc possibility of scvcrc advcrsc rcac-
tions. Civcn thc much lcss signihcant problcms associatcd with oxcarbazc-
pinc, wc will probably scc it prcscribcd morc ohcn and studicd morc closcly.
Omcr Mood StahIzcrs
Scvcral othcr agcnts show promisc fr thc trcatmcnt of bipolar disor-
dcr. Ior thc most part, thc promisc of thcsc mcdications is bascd on clinical
trials in which thc mcdication is addcd to thc rcgimcn of paticnts alrcady
taking an cstablishcd mood stabilizcr such as lithium, but somctimcs a fcw
casc rcports of a thcrapcutic chcct arc cnough to attract thc attcntion of
Pramipcxolc [Mirapcx) is a mcdication that is usually uscd to trcat Par-
kinson`s discasc and rcstlcss- lcg syndromc, it activatcs dopaminc circuits in
thc brain. Scvcral studics havc shown pramipcxolc to bc an chcctivc add-on
trcatmcnt fr bipolar dcprcssion not rcsponding to mood stabilizcrs alonc. ''
As with othcr trcatmcnts that arc cspccially hclpml fr bipolar dcprcssion,
thcrc is a risk of dcvcloping hypomanic or manic symptoms hom taking
5ccausc this mcdication has alrcady bccn approvcd to trcat othcr disor-
dcrs, physicians may prcscribc it to paticnts with bipolar disordcr, a practicc
known as "oh- labcl prcscribing. nc of thc rolcs of thc IOA is to approvc
how manufcturcrs markct pharmaccuticals to physicians. Companics may
only advcrtisc drugs to physicians fr thc trcatmcnt of spccihc symptoms
or a particular diagnosis, and cvcn thcn only ahcr thc agcncy has bccn prc-
scntcd with mountains of data supporting thc drug's chcctivcncss fr that
condition. Thc dctails of that data arc uscd to prcparc thc "labcl of thc drug,
actually a pamphlct- sizcd documcnt callcd thc "packagc inscrt' 5ut sincc
thc IOA docs not rcgulatc thc practicc of mcdicinc, physicians may prc-
scribc any availablc drug fr othcr conditions if, bascd on thcir rcvicw of
availablc rcscarch and thcir judgmcnt and cxpcricncc, thc drug is appropri-
atc to trcat thc paticnt. Whcn thcy usc it to trcat a condition not listcd in thc
IOA "labcl,' this practicc is callcd "oh-labcl prcscribing'
ALL1~S111Z1iL A11L1LiS M j
If taking a mcdication fr an oh-labcl disordcr sccms risky, it may rcas-
surc you to lcarn that most ncw mood stabilizcrs, including valproatc and
lamotriginc, wcrc widcly prcscribcd "oh- labcl fr ycars bcfrc thcy rcccivcd
IOA labcling fr bipolar disordcr.
Thcrc is cvidcncc that - acctyl cystcinc [AC) , an amino acid availablc
in vitamin storcs as a nutritional supplcmcnt, may bc uscml as a mood stabi-
lizcr. '' A small handml of studics cxamining AC as an add-on mcdication
to othcr mood stabilizcrs havc shown vcry promising rcsults, cspccially in
bipolar dcprcssion. This discovcry is cspccially cxciting bccausc thc mccha-
nism of action of AC is vcry dihcrcnt hom that of any othcr mood stabi-
lizcr. AC is a mctabolic prccursor to glutathionc, a powcrml antioxidant
that occurs in brain tissuc, suggcsting that AC, likc othcr mood stabilizcrs,
may work through ncuroprotcctivc mcchanisms.
Anothcr promising agcnt i s riluzolc [Rilutck), a mcdication approvcd
fr thc trcatmcnt of amyotrophic latcral sclcrosis [ALS, somctimcs known
as Lou Cchrig's discasc, ahcr thc fmous bascball playcr of thc I os who
suhcrcd hom it) . Riluzolc has a protcctivc chcct on ncurons, and this is why
it hclps slow thc progrcssion of ALS, a discasc charactcrizcd by progrcssivc
dctcrioration of thc ncrvc cclls that control musclcs. [ Lithium has long bccn
known to havc a similar protcctivc chcct. ) Riluzolc works through thc samc
chcmical pathways that lamotriginc docs. Somc of thc most promising stud-
ics on thc usc of riluzolc in bipolar disordcr havc bccn thosc showing that it
is hclpml in bipolar dcprcssion. ''
Tiagabinc [ Cabitril) and zonisamidc [Zoncgran) arc othcr anti- cpilcpsy
drugs that havc attractcd thc intcrcst of clinical rcscarchcrs on bipolar disor-
dcr. ngoing work may rcsult in thcsc drugs also bcing introduccd as mood-
stabilizing mcdications.
On thc Horzon. Promsng Mcw Approachcs
In thc past dccadc, scicncc has madc almost unbclicvablc progrcss in
undcrstanding thc intricatc workings of thc human brain. This ncw undcr-
standing mcans that, fr thc vcry hrst timc, pharmaccuticals arc bcing dc-
vclopcd bascd on how thcy intcract with spccihc biological systcms in thc
brain. Thanks to work in thc hclds of gcnctics and ncuroscicncc, molccular
pathways havc bccn idcntihcd that sccm to bc involvcd in thc dcvclopmcnt
of thc symptoms of mood disordcrs. Many ncw pharmaccutical agcnts now
bcing tcstcd havc bccn sclcctcd bccausc thcy arc known to havc ccrtain mo-
lccular chccts. In somc cascs, clinical trials arc bcing carricd out on oldcr
mcdications that havc bccn uscd fr dccadcs to trcat othcr mcdical prob-
lcms. o onc suspcctcd that thcsc pharmaccuticals might hclp pcrsons with
bipolar disordcr, but thcy arc substanccs that arc known to work through
somc particular biochcmical proccss that wc now know can go awry in
mood- disordcr paticnts.
A good cxamplc of this "old bccomcs ncw approach is thc intcrcst in
allopurinol, a drug introduccd in thc I6os to trcat gout. Scvcral small clin-
ical trials havc dcmonstratcd that it hclps somc pcoplc with bipolar dcprcs-
sion. '' An cvcn oldcr agcnt is scopolaminc, a drug originally cxtractcd hom
a fmily of poisonous plants in thc nightshadc fmily [jimsonwccd is onc)
that was hrst uscd at thc bcginning of thc twcnticth ccntury as an obstctrical
ancsthctic and is now uscd to trcat motion sickncss. A zoo6 study at thc a-
tional Institutc of Mcntal Hcalth dcmonstratcd "rapid, robust antidcprcssant
rcsponscs in paticnts with bipolar dcprcssion who wcrc givcn scopolaminc
intravcnously. '` In both of thcsc cascs, clinical scicntists wcnt looking fr an
agcnt that was known to ahcct a particular biological pathway in ncurons
ahcr studics by ncuroscicntists implicatcd that pathway in thc dcvclopmcnt
of bipolar disordcr. Thcy wcrc frtunatc to hnd just thc mcdications thcy
wcrc looking fr, though pcrhaps not whcrc thcy cxpcctcd to hnd thcm.
among oldcr trcatmcnts fr, of all things, gout and motion sickncss .
Lntircly ncw pharmaccuticals arc bcing dcvclopcd as wcll, drugs that,
fr now at lcast, bcar only codc namcs assigncd to thcm by thc pharmaccu-
tical companics working on thcm, namcs likc AZO6;6y and LVT IoI. '"
Maybc thc days of accidcntally stumbling upon chcctivc trcatmcnts fr
bipolar disordcr, as happcncd in thc casc of lithium and valproatc, arc com-
ing to an cnd. ldcr drugs arc bcing rcdcploycd and cntircly ncw drugs arc
bcing dcvclopcd bascd on knowlcdgc and undcrstanding of thc biochcmis-
try of bipolar disordcr. Ahcr dccadcs of ncarly aimlcss scarching in thc dark
fr ncw trcatmcnts, bright lights arc indccd on thc horizon.
ALL1~S111Z1iL A11L1LiS M ,
L M A 1 H 7
dcprcssion of bipolar disordcr has bccn dcbatcd fr scvcral dccadcs now.
This is bccausc thcsc mcdications can push a bipolar paticnt hom dcprcs-
sion into a manic statc. [Thc dcvclopmcnt of manic symptoms in paticnts
bcing trcatcd fr tubcrculosis with a mcdication callcd iproniazid is what lcd
to thc dcvclopmcnt of thc class of antidcprcssants callcd mcncam|nccx|dasc
|nb||||crs. )In somc paticnts, antidcprcssants sccm to incrcasc thc cycling of
thcir illncss.
Yct, dcspitc thc risks associatcd with antidcprcssants fr pcrsons with
bipolar illncss, somc paticnts with bipolar disordcr appcar to bcncht hom
thcm and can takc thcm safcly. Lnfrtunatcly, wc don`t yct havc any way of
idcntiing who thosc paticnts arc, so caution is thc byword whcn it comcs
to prcscribing thcsc drugs.
TrcycIc Antdcprcssants
Although tricyclics arc now lcss hcgucntly uscd as antidcprcssants, our
discussion starts with this group bccausc thcsc wcrc thc hrst antidcprcs-
sant mcdications dcvclopcd and bccausc thcy still providc thc standard by
which all promising ncw pharmaccuticals fr thc trcatmcnt of dcprcssion
arc judgcd.
Thcsc drugs arc callcd |r|cyc||csbccausc of thc thrcc rings in thcir chcm-
ical structurc. Although somc tricyclics havc an chcct on scrotonin systcms
in thc brain, thcir primary chcct in thc brain sccms to bc inhibiting rcuptakc
of thc ncurotransmittcr norcpincphrinc by ncurons. Rcmcmbcr that thc rc-
uptakc of ncurotransmittcrs into thc ncuron ahcr thcy havc bccn rclcascd
into thc synaptic clch, and havc donc thcir work signaling thc ncxt ccll, is
thc mcans by which thc synapsc is "rcsct' orcpincphrinc is usually guickly
rcmovcd hom thc synapsc and pumpcd back into thc ccll that rclcascd it in
ordcr to turn oh and rcsct thc systcm. 5y blocking thc rcmoval of norcpi-
ncphrinc, tricyclics sccm to prolong or intcnsify norcpincphrinc's mcssagc
to thc ncxt ccll in somc way.
This chcct of tricyclics on norcpincphrinc in ncurons was onc of thc
hrst chcmical chccts of a mcdication activc in thc brain to bc mcasurcd in thc
laboratory. Thc obscrvation that tricyclics |ncrcascd thc amount of norcpi-
ncphrinc in thc synapsc, along with thc discovcry that ccrtain othcr mcdica-
tions uscd to trcat high blood prcssurc rcduccdnorcpincphrinc-and wcrc
obscrvcd to causc dcprcssion in somc paticnts-lcd to thc carly aminc hy-
pothcsis of thc mood disordcrs. thc thcory that dcprcssion was causcd by
too littlc norcpincphrinc and mania, prcsumably, by too much. Howcvcr,
mrthcr rcscarch indicatcd that tricyclics incrcascd amincs in thc synapsc
within bcursof taking thcm but took wcc/sto bcgin to hclp with dcprcssivc
symptoms, and this lcd to a scarch fr an altcrnativc cxplanation. That scarch
is still going on. Tablc - I lists thc common tricyclics.
Thc principal rcason that tricyclic antidcprcssants arc now lcss hc-
gucntly prcscribcd is thcir many sidc chccts . As with all mcdications, somc
paticnts can takc tricyclics casily and without unplcasant sidc chccts, but
many paticnts havc to put up with a fcw days or cvcn wccks of troublcsomc
sidc chccts to gct thc bcnchts. Iortunatcly, all thc sidc chccts arc dosc- rclatcd,
and most arc tcmporary.
You may rcmcmbcr that Roland Kuhn fund imipraminc, thc hrst tri-
Tnsir /-I Tricyclic antidcprcssants
Pbarmaccu|/ca| namc
rand namc
Asen din
i11PVSSi A11L1LiS M
cyclic, among a group of compounds that had somc antihistaminc chccts.
It's not surprising, thcn, that thcsc mcdications ahcct somc pcoplc thc way
antihistamincs do, causing mild slccpincss and somctimcs what somc of my
paticnts havc callcd a "wcird or "spaccy fccling fr thc hrst day or two
ahcr starting thcm. Tricyclics block anothcr ncurotransmittcr callcd acc|y|-
cbc||nc,which is uscd in thc part of thc ncrvous systcm that rcgulatcs many
"automatic mnctions of thc body such as digcstion. Thcsc an||cbc| |ncry|c
sidc chccts includc a slowing down of thc gastrointcstinal tract, causing con-
stipation and dry mouth. Thc fcusing of thc lcns of thc cyc and cmptying
of thc urinary bladdcr arc also controllcd by this systcm, and tricyclics can
causc blurry vision and urination dimcultics also, although usually only at
high doscs. Paticnts with a history of glaucoma or urinary- tract problcms
should bc monitorcd closcly by thcir physician whilc taking thcsc mcdica-
tions. Tricyclics also causc wcight gain in many paticnts.
Tricyclics arc toxic in largcr amounts and ovcrdoscs arc vcry dangcrous.
Although thc lcthal ovcrdosc is up to twcnty timcs thc normal dosc fr an
adult, childrcn arc morc scnsitivc to thc toxic chccts of thcsc mcdications,
just a handml of tablcts can bc ftal in a small child. Ior this rcason, tricyclic
mcdications must bc scrupulously safcguardcd in houscholds with childrcn.
ScIcctvc Scrotonn Rcuptac Inhhtors
It will comc as no surprisc that a ncw pharmaccutical that had nonc of
thc tricyclic sidc chccts listcd abovc and was not toxic in ovcrdosc causcd
somcthing of a scnsation whcn it was introduccd in I88. That pharmaccuti-
cal was fluoxctinc [Prozac) . Ior a timc it sccmcd that cvcryonc you talkcd to
was cithcr taking Prozac or rcading about it. A Prozac capsulc showcd up on
thc covcrs of Ncwswcc/and Ncwcr/magazincs, and thc drug was fcaturcd
in innumcrablc othcr magazinc and ncwspapcr articlcs.
Lnlikc thc tricyclics, this class of antidcprcssants has littlc dircct cf-
fcct on norcpincphrinc in thc brain but instcad blocks thc rcuptakc of an-
othcr ncurotransmittcr, scrotonin, into ncurons. Thc vcry potcnt and spccihc
scrotonin-rcuptakc-blocking chccts of thcsc agcnts givc this class its namc.
sc|cc||vcscrc|cn|n rcu|a/c|nb||||crs, or SSRIs[tablc ;- z) .
Thc sidc- chcct prohlc of thc SSRIs i s vcry bcnign. Somc paticnts cxpc-
ricncc nausca fr thc hrst couplc of days ahcr starting onc of thc SSRIs, and
a vcry fcw havc diarrhca or vomiting. Hcadachcs arc not uncommon. Thcsc
problcms can ohcn bc allcviatcd by rcstarting thc mcdication at a lowcr dosc,
and thcy tcnd to pass guickly. SSRIs can bc somcwhat stimulating in somc
pcoplc, and whilc this is just what is nccdcd by somc dcprcsscd paticnts,
othcrs fccl unplcasantly ncrvous or "wircd whcn taking thcsc mcdications.
Thc convcrsc can also bc sccn, and slccpincss is somctimcs a sidc chcct. Many
100 M VAi
Tzeir/-2 Sclcctivc scrotonin rcuptakc inhibitors
Pbarmaccu|/ca| namc
rand namc(s)
Celexa Cipramil)
Lexapro Cipralex)
Prozac, Sarafem Erocap, Fluohexal, Lovan, Zactin,
and others)
Paxil, Paxil CR* Aropax, Seroxat, and others)
Zolo6 Altruline, Aremis, Gladem, Besitran, Lustral,
Sealdin, and others)
Nc|e amcs n parcnthcscs arc brands markctcd outsdc thc Lntcd Statcs.
*Slow-rclcasc prcparaton.
paticnts rcport that SSRIs sccm to curb thcir appctitc a bit and noticc somc
wcight loss, cspccially soon ahcr thcy bcgin taking an SSRI. Wcight gain can
also bc a problcm, howcvcr. All of thcsc sidc chccts arc usually noticcd by
paticnts prctty much immcdiatcly, if thcy arc going to occur, nonc of thcm
sncak up ahcr a pcrson has bccn on an SSRI fr wccks or months.
nc problcm that might not bc noticcablc to paticnts until thcy'vc bccn
taking an SSRI fr wccks or months is a changc in scxual mnctioning, spccif-
ically a noticcablc dccrcasc in scxual intcrcst [loss of libido) or a dimculty in
rcaching or inability to rcach orgasm. Tis is a signihcant problcm ahccting
about onc- third of paticnts. A varicty of stratcgics arc availablc fr dcaling
with thcsc problcms whcn thcy occur, so thcy should bc rcportcd to thc
physician. Wcckcnd "vacations hom thc mcdication havc bccn rcportcd to
bc hclpml, as wcll as thc addition of othcr mcdications that sccm to block
thcsc chccts, but somctimcs a switch to an antidcprcssant in anothcr class is
thc only solution.
Whcn I askcd onc of my malc paticnts whcthcr hc was having any scxual
dysmnction hom his ncw antidcprcssant, hc rcplicd that hc thought fluoxc-
tinc had |mrcvcdhis scx lifc, incrcasing his scxual stamina and causing him
to havc morc intcnsc orgasms-a rcmindcr that a list of potcntial mcdica-
tion sidc chccts should ncvcr bc a rcason not to try a particular mcdication.
Plcasant surpriscs somctimcs do occur. Also, a mcdication chcct that causcs
problcms fr somc paticnts can actually bc hclpml fr othcrs, fr cxamplc,
SSRIs havc bccn rcportcd to bc hclpml in trcating prcmaturc cj aculation. '
Mcw Antdcprcssants
Sincc thc carly Ios, many othcr ncw antidcprcssants havc comc onto
thc markct that arcn`t tricyclics and arcn't SSRIs. Sincc most of thcsc phar-
i11PVSSi A11L1LiS M 101
Tzeir;- thcr antidepressants
Pbarmaccu|/ca| namc
rand namc(s)
Wellbutrin, Wellbutrin XL,* Wellbutrin SR*
Cymbalta Davedax, Xeristar, Yentreve, and others)
Remeron Remergil, Zispin, and others)
Serzone ' Dutonin) '
Desyrel Azona, Molipaxin, Sideril, Tombran, and
Enexor, Enexor XR* Efexor, Efexor XR,* and others)
Nc|e amcs n parcnthcscs arc brands markctcd outsdc thc Lntcd Statcs.
*Slow-rclcasc prcparaton.
brands wthdrawn by manuIcturcr bccausc oI rcports oI Ivcr Ilurc.
maccuticals don`t sharc many common fcaturcs, thcrc is no good class namc
fr thcm, although you'll somctimcs scc many of thcm listcd as "atypical or
"sccond- gcncration antidcprcssants [tablc ;- ) . Tcy havc a varicty of cf-
fccts on norcpincphrinc, scrotonin, and othcr ncurotransmittcrs. Somc havc
morc than onc chcct on thcsc systcms, and so thcy arc thought to providc
dihcrcnt ways of manipulating thc chcmical systcms in thc brain that arc
conccrncd with mood. Vcnlafxinc and duloxctinc, fr cxamplc, inhibit thc
rcuptakc of both norcpincphrinc and scrotonin and arc rcfcrrcd to as dual
rcuptakc inhibitors or SRIs, fr scrc|cn|nandncrc|ncbr|ncrcu|a/c |n-
b| |||crs.5upropion is most activc on a dihcrcnt ncurotransmittcr altogcthcr,
dopaminc. Tc sidc- chcct prohlcs of thcsc mcdications vary widcly. Somc
havc a prohlc morc likc that of tricyclics, othcrs morc likc that of SSRIs.
Monoamnc Oxdasc Inhhtors
In thc carly Iy os, a ncw drug that had bccn dcvclopcd fr thc trcat-
mcnt of tubcrculosis was obscrvcd to causc mood clcvation in somc paticnts
who took it fr thcir lung discasc. Ahcr morc ycars of invcstigations, mostly
in Lngland, scvcral papcrs appcarcd that conhrmcd thc thcrapcutic chccts
of iproniazid in paticnts suhcring hom dcprcssion. Shortly ahcrward it was
discovcrcd that iproniazid causcs inactivation of an cnzymc in thc body
that mctabolizcs aminc compounds in thc ncrvous systcm. Tis cnzymc,
callcd mcncam|nccx|dasc,is rcsponsiblc fr gobbling up molcculcs of nor-
cpincphrinc, scrotonin, and scvcral othcr ncurotransmittcrs. Inactivating
monoaminc oxidasc has thc chcct of incrcasing thc amounts of thcsc ncu-
rotransmittcrs in thc ncrvous systcm, and this chcct-in somc as yct poorly
102 M VAi
undcrstood way-may bc how thcsc mcdications allcviatc thc symptoms of
dcprcssion. This class of pharmaccuticals is callcd mcncam|nccx|dasc|nb| |-
||crs, or MOs[tablc ;- () .
Thcrc arc two frms of monoaminc oxidasc i n thc body, MA-A and
MA- 5. Lntil rcccntly, all of thc pharmaccuticals uscd to trcat dcprcssion
wcrc activc in blocking MA-A. In addition to its activity in thc ncrvous
systcm, MA-A is also prcscnt in thc lining of thc intcstinc. Somc naturally
occurring substanccs in fods arc closc cnough chcmically to norcpincph-
rinc to nccd dcactivation bcfrc thcy arc absorbcd into thc bloodstrcam,
and intcstinal MA- A scrvcs this purposc. Thc importancc of this bccomcs
clcar whcn I tcll you that anothcr namc fr norcpincphrinc is adrcna||nca
namc that is probably morc fmiliar to you. Tyraminc, an amino acid that
has adrcnalinc- likc chccts on blood prcssurc and hcart ratc, is prcscnt in
high cnough conccntrations in somc fods to causc dangcrous cardiovascular
problcms in individuals taking MAIs. umcrous pharmaccuticals, includ-
ing thc ingrcdicnts of many ovcr- thc-countcr rcmcdics, also havc adrcn-
alinc-likc chccts. Pcoplc taking MAIs thcrcfrc nccd to obscrvc ccrtain
dictary rcstrictions and, cvcn morc importantly, must scruu|cus|yrcad thc
labcls of any ovcr-thc-countcr mcdication thcy arc considcring-or bcttcr
yct, consult thcir pharmacist bcfrc taking any pharmaccutical thcy buy
ovcr thc countcr.
MAIs also intcract with othcr mcdications that arc prcscribcd or com-
monly uscd in cmcrgcncy rooms fr various problcms. Pcoplc taking MA Is
must bc surc to infrm all physicians who trcat thcm that thcy arc on this
typc of mcdication. And thcy should considcr wcaring an alcrting bracclct
so that, should thcy bc brought into an cmcrgcncy room unconscious or
othcrwisc unablc to communicatc, thc bracclct can communicatc to LR pcr-
sonncl that thcy arc taking an MAI.
Rcccntly a pharmaccutical has bccn dcvclopcd that blocks primarily
MA-5, thc othcr frm of MA in thc body. MA- 5 is prcscnt almost cn-
tircly in thc brain and is not involvcd in blocking tyraminc absorption in thc
intcstinc. Thc big advantagc of an MA- 5 inhibitor ovcr an MA-A inhib-
itor, thcn, is that pcrsons taking it wouldn`t havc to bc on a spccial dict. This
Tnsir ;- Monoaminc oxidasc inhibitors [MAIs)
Pbarmaccu|/ca| namc
*1c scIcglnc patch.
rand namc(s)
Eldepryl, Emsam transdermal system*
i11PVSSi A11L1LiS M 10j
drug, callcd sc|cy|||nc, has bccn uscd fr thc trcatmcnt of Parkinson's discasc
fr scvcral ycars. Thcrc wcrc carly attcmpts to usc it as an antidcprcssant,
but it was discovcrcd that thc rcguircd doscs wcrc so high whcn takcn in
pill frm that sclcgilinc ahcctcd |c|bfrms of MA [A and 5) -that is, thc
spccihcity fr MA- 5 is lost. This mcant that paticnts taking it would still
nccd to watch thcir dict fr sourccs of tyraminc-no advantagc thcrc| Thcn
somconc camc up with thc idca of making a sclcgilinc a|cb,so that thc drug
is absorbcd through thc skin rathcr than takcn orally. Thc patch turns out to
havc two important advantagcs. Iirst, bccausc thc sclcgilinc is morc dircctly
absorbcd into thc bloodstrcam, it can bc givcn at a lowcr dosc and maintain
its spccihcity fr MA- 5. Sccond, sincc it docsn`t travcl through thc intcs-
tinc, it docsn't ahcct thc MA-A locatcd thcrc ncarly as much as thc oldcr
MA Is did. Thus, thc sclcgilinc patch is an casicr way of taking an MAI,
with fcwcr sidc chccts and lcss worry about tyraminc- rich fods.
MAIs can havc othcr sidc chccts, too. Thcy can bc stimulating and
causc insomnia. Ior this rcason, taking thc oral prcparations at bcdtimc
should bc avoidcd. Oizzy spclls, cspccially whcn onc suddcnly gcts up hom
lying down, can occur. MAIs block a blood- prcssurc rcflcx that usually
maintains blood prcssurc whcn wc stand up, and thc suddcn drop in blood
prcssurc on standing [callcd cr|bcs|a||c byc|cns|cn) causcs lighthcadcd-
ncss. Wcight gain and scxual dysmnction arc othcr sidc chccts.
5ccausc of thcsc issucs, MAIs arc most ohcn prcscribcd to paticnts
who havc filcd to bcncht hom othcr antidcprcssants. This said, thcy arc
somctimcs unigucly chcctivc, indccd arc "miraclc drugs,' fr somc paticnts
who havc bccn hclpcd by no othcr antidcprcssants. I think cvcry psychiatrist
I'vc cvcr spokcn with has had thc cxpcricncc of chcctivcly trcating a particu-
lar paticnt with an MAI ahcr no othcr antidcprcssant had hclpcd.
Trcatng BpoIar cprcsson
Thc obscrvation that antidcprcssants can causc manic symptoms in pcr-
sons with bipolar disordcr has bccn conhrmcd again and again. Pcrhaps morc
worrisomc is thc obscrvation that antidcprcssants may causc an accclcration
of thc illncss in somc paticnts. Somc pcrsons with bipolar disordcr cxpcri-
cncc incrcascd cycling of thcir mood cpisodcs and cvcn switch to a pcriod of
rapid cycling.
In thc latc Ios, thc ational Institutc of Mcntal Hcalth sponsorcd a
largc, multiccntcr study of thc trcatmcnt of bipolar disordcr callcd thc Sys-
tcmatic Trcatmcnt Lnhanccmcnt Program fr 5ipolar Oisordcr [ STLP- 5O) .
This study cnrollcd morc than (,ooo pcoplc with bipolar disordcr, fllowcd
thcm ovcr scvcral ycars whilc thcy wcrc rccciving trcatmcnt, and cvaluatcd
thc succcss or filurc of various intcrvcntions. nc of thc surprising hnd-
10q M VAi
ings of thc study was in a subgroup of jO paticnts who dcvclopcd dcprcs-
sion during thc coursc of thc study. About half of thcsc paticnts wcrc thcn
prcscribcd an antidcprcssant in addition to thcir mood stabilizcr, whilc thc
othcrs staycd on thc mood stabilizcr alonc. At thc cnd of about six months,
antidcprcssant mcdications appcarcd to havc ohcrcd no bcncht whatso-
cvcr-nor did thc paticnts who took an antidcprcssant havc any morc prob-
lcms with manic symptoms than thc paticnts who took only a mood stabi-
lizcr.' ow, this sccms to fly in thc fcc of dccadcs of rcscarch and clinical
cxpcricncc dcmonstrating what I said at thc bcginning of this chaptcr-that
somc bipolar paticnts nccd, bcncht hom, and can safcly takc antidcprcs-
sants . 5ut it makcs thc point strongly that thosc paticnts arc thc cxccption,
not thc rulc, and that most bipolar paticnts should probably avoid taking
antidcprcssant mcdications .
Studics on thc issuc of incrcasing mania and rapid cycling indicatc that
somc paticnts arc at morc risk than othcrs fr a worscning of thcir situa-
tion with antidcprcssant trcatmcnt. Lnfrtunatcly, it is not possiblc to say
with ccrtainty who is and who is not at risk. 5ipolar I paticnts sccm to bc
at grcatcr risk than bipolar II paticnts, womcn arc at grcatcr risk than mcn,
and paticnts who alrcady havc a history of morc rapid cycling-cithcr morc
mll-blown cpisodcs or a tcndcncy toward cyclothymia [continuous low- am-
plitudc cycling) bctwccn mll-blown cpisodcs-arc at grcatcr risk. Morcovcr,
somc antidcprcssant mcdications sccm to bc riskicr than othcrs. A fcw stud-
ics indicatc that bupropion, paroxctinc, and MA Is may bc safcr than othcr
antidcprcssants-that is, lcss likcly to prccipitatc mania [and, by implica-
tion, pcrhaps lcss likcly to incrcasc cycling) .
Anothcr hnding hom thc STLP- 5O study was that ahcr somc paticnts
with bipolar disordcr takc an antidcprcssant and sccm to rccovcr hom a
scvcrc dcprcssion, thcy may noticc morc of thc fcclings of tcnsc uncasi-
ncss that psychiatrists call "dysphoria,' along with a smoldcring irritability
and slccp disturbanccs. Thc rcscarchcrs rcfcrrcd to this sct of symptoms as
"ACIO,' short fr an||dcrcssan|-asscc|a|cd cbrcn|c |rr||a||c dysbcr|a, and
thcy fund that thcsc paticnts wcrc guitc impaircd by thcsc symptoms. `Thc
rcscarchcrs had alrcady suspcctcd that antidcprcssants wcrc thc causc of this
problcm, and so whcn thcy lookcd fr paticnts with thc triad of chronic ir-
ritability, dysphoria, and slccp disturbanccs among STLP- 5O paticnts, thcy
notcd who had or had not takcn an antidcprcssant along with a mood stabi-
lizcr. Thc rcsults wcrc uncguivocal. Thcy fund that thc paticnts with thcsc
symptoms who had takcn an antidcprcssant outnumbcrcd paticnts taking
only a mood stabilizcr by tcn to onc.
So what do wc concludc hom all this I think a rcasonablc approach is
to rccommcnd a cautious and closcly obscrvcd trial of onc of thc safcr anti-
dcprcssants fr paticnts who still havc scrious dcprcssion dcspitc optimiza-
i11PVSSi A11L1LiS M 10j
tion of mood- stabilizcr trcatmcnt, but only if thcy havc ncvcr had a prcvious
problcm with an antidcprcssant. At thc hrst sign of irritability, dysphoria, or
slccp disturbancc, strong considcration should bc givcn to stopping thc an-
tidcprcssant. I think it's also fir to concludc that trying onc antidcprcssant
ahcr anothcr in bipolar paticnts should bc avoidcd, thc rcscarch litcraturc
rcally docs support thc idca that most bipolar paticnts will nc|bcncht hom
an antidcprcssant.
Pcrhaps morc than any othcr trcatmcnt issucs, thc gucstions surround-
ing thc usc of antidcprcssants in bipolar disordcr cmphasizc thc nccd fr
individualization of trcatmcnt fr cvcry paticnt. Thcrc arc no hard- and-fst
rulcs fr whcn, why, or how to usc an antidcprcssant fr bipolar paticnts . Pa-
ticnt and physician nccd to communicatc clcarly and honcstly about cvcry
aspcct of symptoms and trcatmcnt to achicvc thc bcst trcatmcnt outcomc.
10 M VAi
L M A 1 K 7
antipsychotic mcdications is thcir unfrtunatc namc. Psycbc||cis an imprc-
cisc tcrm at bcst, and thcsc mcdications havc many morc uscs than simply
trcating psychotic symptoms.
A psychosis can bc thought of as a mcntal statc or disordcr in which thc
ahcctcd pcrson's ability to comprchcnd his or hcr cnvironmcnt and rcact
to it appropriatcly is scvcrcly impaircd. Thc layman`s dchnition of sycbc||c
might bc "out of touch with rcality' Thc pcrson who is hcaring voiccs [hav-
ing hallucinations) or who has bizarrc idiosyncratic bclicfs [dclusions) is
psychotic. Thc word also connotcs a scvcrc disorganization of thinking and
bchavior, usually with rcstlcssncss and agitation. Thc manic syndromc is a
good cxamplc of a statc of psychosis, and wc havc alrcady talkcd about "psy-
chotic fcaturcs in dcprcssion.
In thc Ios a group of pharmaccutical compounds callcd bcnc|b|-
ac|ncs wcrc synthcsizcd in Luropc and wcrc fund to havc antihistaminc
and scdativc propcrtics. nc in particular, chlorpromazinc, was fund to bc
vcry uscml in surgical ancsthcsia bccausc it dccpcncd ancsthctic scdation
morc safcly than othcr availablc agcnts. In thc carly Iyos, two Ircnch psy-
chiatrists carricd out scvcral clinical trials using chlorpromazinc to trcat
highly agitatcd paticnts suhcring hom schizophrcnia and mania. Thcy had
hopcd thc drug would providc scdation fr thcsc vcry sick paticnts, which it
did-but thcsc astutc clinicians noticcd that thc mcdication did much morc.
In addition to its guicting and slccp- promoting chccts, chlorpromazinc
madc thc hallucinations and bizarrc dclusional bclicfs of many paticnts with
schizophrcnia practically disappcar. It also dccrcascd thc scvcrity of thc dis-
organization of thinking and agitatcd bchavior sccn in paticnts with acutc
mania. Chlorpromazinc, in othcr words, had a scc]cchcct on thc clustcr of
symptoms usually rcfcrrcd to as "psychotic symptoms, and thus thc namc
fr this group camc about. an||sycbc||cmcd|ca||cns. ccasionally thcy arc
still rcfcrrcd to as ncurc|c||c mcd|ca||cns [or ncurc|c||cs), hom ncurc|c-
||quc, thc Ircnch word [coincd hom Crcck roots) that mcans roughly "af-
fccting thc ncrvous systcm' Thc tcrm ma)cr |ranqu|| |ccrs was hcgucntly
uscd fr thcsc mcdications at onc timc [with thc tcrm m|ncr|ranqu|||ccrs
uscd fr slccp and anxicty mcdications), but thcsc agcnts arc much morc
than just "tranguilizcrs,' and this tcrm has, frtunatcly, fllcn out of fvor.
In thc I8os a ncw antipsychotic mcdication was dcvclopcd that had
much morc chcct on thc ncurotransmittcr scrotonin than thc othcr anti-
psychotics did. In thc ycars sincc, many morc of thcsc drugs havc bccn dc-
vclopcd. This group of mcdications has bccn a vcry important dcvclopmcnt
in psychiatry, fr rcasons I'll discuss bclow. ow antipsychotic mcdications
arc usually dividcd into two groups, thc original group of mcdications bcing
callcd thc |y|ca|an||sycbc||cs.Thc ncwcr group, which havc morc chcct on
thc scrotonin systcm than thcir prcdcccssors, arc callcd thc a|y|ca|an||sy-
cbc||cs. In this chaptcr wc'll takc a look at cach group in turn.
TypcaI Antpsychotc Mcdcatons
As wc saw in part I of this book, cpisodcs of bipolar disordcr-both dc-
prcssion and mania-can somctimcs includc cxtrcmcly hightcning mcntal
symptoms and dangcrously disturbcd bchaviors. And, as wc saw in chap-
tcrs 6 and , mood stabilizcrs and antidcprcssants somctimcs takc wccks
to bcgin working. What can bc donc to slow down thc racing thoughts, thc
prcssurcd, bursting ovcractivity of thc manic paticnt, bcfrc lithium starts
working This is whcrc thc typical antipsychotic mcdications havc bccn usc-
ml [tablc 8- I) . 5ccausc thcir calming chccts bcgin almost immcdiatcly, thcsc
mcdications arc cspccially uscml in acutc mania and arc hcgucntly part of
thc trcatmcnt fr thc scvcrcly ill manic paticnt. In cascs of dcprcssion whcrc
thc paticnt is highly rcstlcss and agitatcd, thcy can havc similar bcnchcial
chccts .
Thc main chcmical chcct of all antipsychotics is to block dopaminc rc-
ccptors in thc brain. cural circuits that usc dopaminc as thcir ncurotrans-
mittcr may bc dysmnctional in somc way in pcoplc with schizophrcnia, and
this situation may causc thc bizarrc hallucinations and disordcrs of think-
ing typical of that illncss. Antipsychotic mcdications may work by ahccting
10 M VAi
Tablc 8-I Tyical antipsychotic mcdications
Pbarmaccu|/ca| namc
rand namc
Nc|e Sdc chccts ncIudc scdaton, antcholncrgc chccts, and cxtrapyramdaI chccts scc
thcsc systcms in somc as yct unknown way. Whcthcr thc mcdications allcvi-
atc thc psychotic symptoms that somctimcs complicatc bipolar disordcr in a
similar fshion is unknown.
Tc typical antipsychotic mcdications wcrc oncc callcd "maj or tranguil-
izcrs bccausc thcy arc, wcll, tranguilizcrs-in a maj or way. Somc arc morc
scdating than othcrs, but all can bc prctty powcrml scdativcs, cspccially in
highcr doscs. Tcy can causc somc of thc samc anticholincrgic sidc chccts
as tricyclic antidcprcssants. dry mouth, constipation, and blurrcd vision.
Pcoplc sccm to accommodatc to thcsc sidc chccts ahcr a pcriod that rangcs
hom days to wccks.
Tc main problcm with most of thcsc mcdications is thcir chcct on mus-
clc tonc and movcmcnt, sidc chccts that arc causcd by thc dopaminc block-
adc that thcy causc. In tcxtbook discussions of thcsc mcdications, you will
scc thcsc problcms rcfcrrcd to as cx|rayram|da|sym|cms, or simply PS.
Oopaminc is thc main ncurotransmittcr uscd in a complcx circuit of brain
arcas callcd thc cx|rayram|da|sys|cm,which coordinatcs movcmcnt. [Tc
tcrm cx|rayram|da|contrasts this systcm with anothcr systcm, callcd thc
yram|da|sys|cm bccausc its main hbcrs arc carricd in triangular bundlcs
into thc spinal cord thc "spinal pyramids or "pyramidal tract] . ) Tc pyra-
midal systcm controls thc guick, accuratc cxccution of hnc musclc movc-
mcnt, and thc cxtrapyramidal systcm makcs surc that thc rcst of thc body
movcs as nccdcd fr thc smooth and graccml cxccution of thcsc movcmcnts.
Antipsychotic mcdications, by blocking thc dopaminc rcccptors in thcsc
ccntcrs, can causc a varicty of sidc chccts that ahcct movcmcnt.
i1PSYLHL1L A11L1LiS M 10
nc of thcsc is scudc-ar/|nscn|sm. You may know that pcrsons suf-
fcring hom Parkinson`s discasc havc a slowcd and shuming walk, sccm to
losc fcial cxprcssion bccausc of stihncss of thcir fcial musclcs, and also
havc trcmbling of thcir hands. Pscudo- parkinsonism consists of thcsc samc
Anothcr cxtrapyramidal sidc chcct is thc acu|c dys|cn|crcac||cn. This
is a suddcn muscular spasm, morc common in young malcs than in othcr
paticnts, that usually involvcs thc tonguc and fcial and ncck musclcs. Pco-
plc taking antipsychotic mcdications can also dcvclop a vcry uncomfrtablc
rcstlcssncss callcd a/a|b|s|a. This is fclt mostly in thc lcgs, so that thc indi-
vidual fccls thc nccd to walk or pacc.
Iortunatcly, all thcsc sidc chccts arc trcatablc, cithcr by lowcring thc
dosc of mcdication or by adding onc of scvcral mcdications that arc also
uscd to trcat Parkinson's discasc. Although uncomfrtablc, thcsc sidc chccts
arc not dangcrous and usually rcspond guickly to trcatmcnt oncc thcy arc
cncountcrcd and idcntihcd.
Most of thc typical antipsychotic mcdications can, ovcr a pcriod of ycars,
causc a sidc chcct callcd |ard|vcdys/|ncs|a, or 7D fr short. This consists
of rcpctitivc involuntary movcmcnts, usually of thc fcial musclcs-usually
chcwing, blinking, or lip-pursing movcmcnts. Thcrc is no good trcatmcnt
fr TDothcr than lowcring thc dosc of thc mcdication, and occasionally it
will nccd to bc discontinucd. Wc uscd to worry a lot about TDbccausc somc
paticnts who dcvclopcd it sccmcd to continuc to havc thcsc movcmcnts
cvcn ahcr thc mcdication was stoppcd. 5ut two fctors arc calming thcsc
worrics. thc discovcry that most TDsymptoms dccvcntually go away with
timc and, morc importantly, thc dcvclopmcnt of thc atypical antipsychotic
mcdications, which do not sccm to causc TDvcry ohcn.
I want to cmphasizc that cxtrapyramidal symptoms arc usually casily
trcatcd and arc not dangcrous. 5ut thc symptoms of bipolar disordcr that thc
antipsychotic mcdications arc usually uscd to trcat arccxtrcmcly dangcrous.
Thcsc mcdications arc powcrml agcnts, and thcy nccd to bc uscd carcmlly
and fr thc shortcst pcriod of timc possiblc, but fr thc prcscnt, at lcast, thcy
arc ncarly irrcplaccablc in trcating thc most dangcrous and most tcrriblc
symptoms of scvcrc mania and psychotic dcprcssion.
AtypcaI Antpsychotc Mcdcatons
As is probably apparcnt hom thc frcgoing paragraphs, thcrc is room
fr improvcmcnt in thc antipsychotic mcdications . ot only arc thc cxtra-
pyramidal symptoms uncomfrtablc, but it is usually ncccssary to add an-
othcr mcdication to control thcm-and thc morc dihcrcnt mcdications a
110 M VAi
Tzeir8-z Atyical antipsychotic mcdications
Pbarmaccu|/ca| namc rand namc(s)
Aripiprazole Abili(
Asenapine Saphris
Clozapine Clozaril
Iloperidone Fanapt
Lurasidone Latuda
Olanzapine Zyrexa, Zyrexa Zydis
Paliperidone Invcga
Quetiapine Seroquel
Risperidone Risperdal
Ziprasidone Geodon
pcrson takcs, thc morc likcly hc is to havc problcms with sidc chccts and
drug intcractions. So it crcatcd guitc a stir whcn a ncw group of antipsy-
chotic mcdications was introduccd, antipsychotics that don't sccm to causc
LPS. Lvcn morc good ncws was that thcsc mcdications sccmcd to work bct-
tcr than thcir prcdcccssors. nc articlc in thc Amcr|can)curna|c}Psycb|a|ry
callcd thc hrst of thcsc ncw agcnts "arguably thc most signihcant dcvclop-
mcnt in antipsychotic drug thcrapy sincc thc advcnt of chlorpromazinc' '
Tcsc atypical antipsychotic mcdications [tablc 8-z)arc dcsignatcd a|y-
|ca|bccausc, although thcy block dopaminc rcccptors, just as thcir prcdcccs-
sors do [though not as potcntly), thcy dihcr hom thc typical antipsychotics
in that thcy arc also activc at scrotonin rcccptors. Tcir doublc action sccms
to havc two chccts. cxtrapyramidal symptoms do not appcar ncarly as ohcn,
and thcsc mcdications sccm to havc signihcant mood-stabilizing chccts.
Tc hrst atypical antipsychotic, c|cca|nc,was synthcsizcd in thc labora-
tory in thc I6os but was not markctcd in thc Lnitcd Statcs until Io. nc
of thc rcasons it took so long fr clozapinc to gct onto thc markct is that, in
about I pcrccnt of paticnts who takc it, it causcs a vcry dangcrous drop in thc
numbcr of whitc blood cclls [callcd ayanu|ccy|cs|s).

Tis problcm might

havc mcant thc cnd fr clozapinc as a ncw mcdication, cxccpt that it was
fund to bc highly chcctivc in trcating paticnts with schizophrcnia who had
dcrivcd littlc bcncht hom traditional antipsychotic mcdications. Oramatic
casc studics of paticnts with chronic trcatmcnt-rcsistant schizophrcnia who
basically "awakcncd hom ycars of unrclcnting psychotic symptoms ahcr
thcy startcd clozapinc sustaincd thc intcrcst of clinicians and pharmaccu-
tical rcscarchcrs. Whcn it was discovcrcd that thc risk of agranulocytosis
could bc substantially rcduccd if thc paticnt had hcr whitc blood ccll count
i1PSYLHL1L A11L1LiS M 111
monitorcd monthly, clozapinc trcatmcnt bccamc availablc to largcr groups
of paticnts, and bcfrc long, trcatmcnt-rcsistant mood- disordcr paticnts wcrc
trcatcd with it as wcll.
Thcrc arc now many studics of thc usc of clozapinc fr pcoplc with
trcatmcnt-rcsistant bipolar and schizoahcctivc disordcr. A ycar ahcr cloza-
pinc camc onto thc markct, a lcttcr to thc cditor of thc )curna| c}C||n|ca|
Psycbcbarmacc|cyy rcportcd that clozapinc had bccn chcctivc in trcating
two rapid- cycling bipolar paticnts "who wcrc rcsistant to all convcntional
trcatmcnt'' nc paticnt was a frty- cight-ycar- old woman who had bccn
vcry ill fr morc than thirty ycars, had startcd rapid cycling about hvc ycars
prcviously, and had bccn almost constantly cycling bctwccn dclusional dc-
prcssions and dysphoric mania fr a wholc ycar bcfrc starting on clozapinc.
Thc authors statcd that ahcr thc woman had bccn taking clozapinc alonc
fr thrcc months, "hcr mood swings complctcly stoppcd' Thc casc rcport
indicatcs that thcrc wcrc cpisodcs of brcakthrough manic and dcprcssivc
symptoms, but thc paticnt had donc rcmarkably bcttcr on clozapinc. [This
casc illustratcs why somc paticnts, at lcast, arc willing to pay thc pricc of thc
nccdcd blood tcsts. )
Anothcr study lookcd at thc usc of clozapinc in twcnty-hvc acutcly
manic paticnts "fr whom lithium, anticonvulsants and traditional] ncuro-
lcptics had bccn inchcctivc, had produccd intolcrablc sidc chccts, or both''
Almost thrcc- guartcrs of thc paticnts had "markcd improvcmcnt in thcir
manic symptoms. Thc answcr to thc gucstion poscd in a I articlc titlc, "Is
Clozapinc a Mood Stabilizcr sccms to bc an cmphatic ycs. `
In thc ycars sincc thc introduction of clozapinc, many othcr atypical
antipsychotic mcdications that do nc| causc blood count problcms havc
comc along, and thcir introduction has substantially cxpandcd thc numbcr
of trcatmcnt options fr bipolar disordcr. Morc and morc cvidcncc is cmcrg-
ing that thc atypical antipsychotic mcdications arc hclpml in all phascs of
bipolar disordcr-mania and dcprcssion-as wcll as fr ongoing trcatmcnt
to prcvcnt rclapsc [somctimcs known as maintcnancc trcatmcnt) . Thc rcally
good ncws is that thcsc mcdications havc vcry signihcant antidcprcssant
chccts in many paticnts [anothcr rcason why calling thcm "antipsychotic
mcdications is inaccuratc) . In 2OO2, just ahcr thc hrst atypicals introduccd
ahcr clozapinc appcarcd, thc )curna| c} C||n|ca| Psycbcbarmacc|cg pub-
lishcd a lcttcr to thc cditor titlcd, "Arc thc Atypical Antipsychotic Orugs An-
tidcprcssants" ncc again thc answcr is a dchnitc ycs, and in subscgucnt
ycars, this fct has bccn bornc out in study ahcr study.
Practicing psychiatrists [including this onc) will tcll you that somc of
thc atypicals sccm to bc morc antimanic and othcrs morc antidcprcssant in
thcir chcct. Lnfrtunatcly, rcscarch that might bcar this out by comparing
112 M VAi
thc chccts of dihcrcnt atypicals fr mania and fr bipolar dcprcssion has not
bccn donc.
I should also mcntion that scvcral of thc ncwcr atypicals arc not labclcd
by thc Iood and Orug Administration fr usc in bipolar disordcr, mcaning
that prcscribing thcm to bipolar paticnts is tcchnically "oh- labcl' [Rcmcm-
bcr that physicians may prcscribc any availablc drug fr a condition if, bascd
on thcir rcvicw of availablc rcscarch and thcir judgmcnt and cxpcricncc,
thc drug is appropriatc to trcat thc paticnt. Whcn this is fr a condition not
listcd in thc IOA "labcl thc practicc is callcd "oh- labcl prcscribing' )
f thc atypical antipsychotics, only clozapinc causcs thc blood-count
problcm that rcguircs hcgucnt blood counts. onc of thc atypical antipsy-
chotics causc LPS cxccpt at high doscs. High doscs can also triggcr thc othcr
sidc chccts that thc traditional antipsychotic mcdications causc. anticholin-
crgic sidc chccts and scdation.
Thc most signihcant sidc- chcct problcm with thc atypical antipsychotic
mcdications has bccn thcir tcndcncy to makc somc individuals gain wcight
and dcvclop such obcsity-rclatcd problcms as high cholcstcrol and cvcn di-
abctcs [tablc 8- ) . ot all individuals dcvclop thcsc problcms, but attcntion
to dict and wcight issucs is vcry important fr pcrsons taking thcsc mcdica-
tions, cspccially fr paticnts who takc thcm ovcr a long tcrm. Thc primary
mcchanism fr thc wcight gain associatcd with thc atypical antipsychotics
sccms to bc stimulation of thc appctitc ccntcr of thc brain, although it has
also bccn suggcstcd that thcsc mcdications ahcct scvcral hormoncs that
control how thc body handlcs calorics and storcs ft. Somc of thc atypical
antipsychotics arc morc likcly to causc wcight gain than othcrs, in fct, scv-
cral sccm rclativcly wcight ncutral-that is, thcy sccm to havc littlc or no
chcct on wcight.
Tzeir8- Wcight gain risks of agical antipsychotics
Higher risk

Lower risk
Scurce Oata hom 1. baptsta, . M. Kn, S. bcauIcu, and L. A. dc baptsta, "Obcsty and
Kclatcd MctaboIc Abnormaltcs durng Orug Admnstraton. Mcchansms, Managcmcnt,
and Kcscarch Icrspcctvcs, Pharmaccs)ch|a|r) j, no. 6 zooz). zo-.
*cgIgblc chcct on wcght.
i1PSYLHL1L A11L1LiS M 11j
Thc wcight-ncutral agcnts would sccm to bc prcfcrablc fr alrcady obcsc
paticnts and fr paticnts with diabctcs or a fmily history of diabctcs . 5lood
tcsts fr diabctcs and high cholcstcrol should bc donc at thc bcginning of
trcatmcnt and rcgularly thcrcahcr in paticnts taking antipsychotics fr main-
tcnancc trcatmcnt. All paticnts taking atypical antipsychotics should takc
stcps to control possiblc wcight gain by paying attcntion to thcir dict and
gctting rcgular cxcrcisc.
11q M VAi
L M A 1 H V
dDU I1O1d1j U1OHOD1S
provcd hclpml in thc trcatmcnt of bipolar disordcr. Somc arc sym|cma||c
|rca|mcn|s, mcaning that thcy trcat symptoms rathcr than thc undcrlying
disordcr and thcrcfrc arc usually uscd fr only a short timc. thcrs arc
mcdications that ahcct mnctioning in anothcr body systcm that is import-
ant fr normal mood rcgulation.
Slccplcssncss and anxicty arc vcry common problcms fr pcrsons with
bipolar disordcr. As wc will scc in chaptcr I6, slccp dcprivation is ohcn vcry
dcstabilizing fr such pcrsons. Anxicty raiscs thc lcvcls of strcss hormoncs
likc cortisol in thc body, and thcrcfrc kccping this uncomfrtablc symptom
in chcck is an important part of staying wcll.
Mcdcatons mr Anxcty and SIccp sturhanccs
Thc bcnzodiazcpinc mcdications rcprcscntcd a major advancc in thc
trcatmcnt of psychiatric symptoms whcn thcy wcrc hrst dcvclopcd, and thcy
continuc to bc widcly prcscribcd [tablc - I ) . Thcy ohcn havc a placc in thc
trcatmcnt of bipolar disordcr bccausc thcy arc highly chcctivc fr thc trcat-
mcnt of anxicty and insomnia and, in highcr doscs, arc safc and chcctivc
scdativcs. If this sounds too good to bc truc and you'rc wondcring if thcrc's a
hiddcn drawback, thcrc is. Thcsc mcdications can bc abuscd, it's possiblc to
bccomc psychologically dcpcndcnt on thcm and cvcn physically addictcd to
Tzeir- i 5cnzodiazcpinc mcdications
Pbarmaccu|/ca| namc rand namc
Alprazolam Xanax
Chlordiazcpoxidc Librium
Clonazcpam Klonopin
Clorazcpatc Tranxcnc
Diazcpam Valium
Lorazcpam Ativan
Nc|e 1csc mcdcatons arc bcst thought oI as tcmporary agcnts and arc hcgucntIy
prcscrbcd r occasonal "as-nccdcd usc.
thcm. [Withdrawal symptoms in pcrsons taking high doscs of thcsc mcdi-
cations can includc vcry scrious problcms such as scizurcs. ) Morcovcr, thcir
scdating chccts dccrcasc ovcr timc, and ahcr scvcral wccks of usc, thcir cf-
fcctivcncss as tranguilizcrs dccrcascs. Ior thcsc rcasons bcnzodiazcpincs arc
bcst thought of as tcmporary mcasurcs.
5cnzodiazcpincs rcally havc two main uscs in trcating bipolar disordcr.
thcy arc uscd to trcat paticnts who arc vcry sick and to trcat paticnts who arc
doing vcry wcll. This sccms to bc a contradiction, docsn`t it Thc cxplana-
tion is in thc doscs uscd and how thc mcdications arc combincd with othcr
mcdications. In acutcly manic paticnts, thc short- acting bcnzodiazcpinc lo-
razcpam [Ativan) can bc an chcctivc short- tcrm tranguilizcr, cspccially in
combination with a typical antipsychotic mcdication likc halopcridol [ Hal-
dol) . This combination is vcry fmiliar to psychiatrists working in cmcr-
gcncy scttings, bccausc it works guickly and chcctivcly in calming cvcn thc
most agitatcd paticnts. A vcry ill manic paticnt, pcrhaps dclusional and agi-
tatcd, who hasn't slcpt fr days can bc aslccp lcss than an hour ahcr rccciving
this combination, cspccially by injcction. Thc longcr- acting bcnzodiazcpinc
clonazcpam [Klonopin) has also bccn uscd and cxtcnsivcly studicd in thc
trcatmcnt of acutc manic symptoms and appcars to bc anothcr chcctivc ad-
junct mcdication.
Thcsc mcdications arc not mood stabilizcrs and arc not chcctivc in
trcating hallucinations or dclusions, but as scdativcs thcy arc unsurpasscd.
Rcmcmbcr that bcfrc chcctivc psychiatric mcdications bccamc availablc,
paticnts with scvcrc mania dicd of thc physical strcss of thc manic statc. 5y
simply slowing manic paticnts down fr a fcw hours or days until antipsy-
chotic mcdications and mood-stabilizing mcdications start working, bcnzo-
diazcpincs can bc litcrally lifcsaving.
At thc othcr cnd of thc spcctrum of illncss scvcrity, paticnts who arc not
having scvcrc mood symptoms can safcly takc thcsc mcdications fr anxi-
cty symptoms and insomnia. Ouring pcriods of unavoidablc psychological
11 M VAi
strcss, such as ahcr thc dcath of a lovcd onc, bcnzodiazcpinc mcdications
can hclp with thc insomnia and lcsscn thc psychological tcnsion that may
bring on mood symptoms in bipolar paticnts. It's important to cmphasizc
hcrc that thcsc mcdications should nc|bc uscd as substitutcs fr making
changcs to chronically strcssml situations. A pcrson who hnds that hc fccls
thc nccd to takc a scdativc to dcal with cvcryday situations is wcll on his
way to psychological dcpcndcncc on tranguilizcrs, mcdication abusc, and
addiction. Wc'll discuss this in morc dcpth in chaptcr i, .
Thcrc's anothcr way thcsc mcdications arc uscd, and that is in trcating
paticnts who havc anxicty disordcrs. Anxicty disordcrs [such as rccurrcnt
panic attacks) arc chcctivcly trcatcd with bcnzodiazcpincs. Thc conncc-
tions bctwccn thc mood disordcrs and anxicty disordcrs arc poorly undcr-
stood, but thcrc arc ccrtainly somc pcoplc who nccd trcatmcnt fr both.
Thc trcatmcnt of panic disordcr and othcr scvcrc anxicty disordcrs somc-
timcs involvcs taking bcnzodiazcpinc mcdications on a longcr-tcrm basis,
but prolongcd usc ofbcnzodiazcpincs is thc cxccption rathcr than thc rulc in
trcating bipolar disordcrs, and any usc rcguircs closc monitoring.
Two mcdications dcvclopcd as trcatmcnt fr cpilcpsy havc provcd to bc
vcry hclpml i n paticnts with anxicty problcms. 5oth arc activc in a ncuro-
rcccptor systcm that is known to bc involvcd with anxicty, thc CA5A path-
way [fr gamma aminobutyric acid), and thcir namcs rcflcct this. gu|upcn-
tin [curontin) and prcgu|ulin [Lyrica) . Thcsc mcdications havc scvcral
advantagcs fr trcating thc anxicty that can bc associatcd with bipolar dis-
ordcr. Thc hrst is that thcrc is littlc or no risk of dcvcloping a psychological
dcpcndcncc on thcm. Cabapcntin is not a "controllcd substancc in IOA
parlancc, and although prcgabalin is, it has bccn assigncd thc lowcst possiblc
risk rating, schcdulc V [othcr schcdulc V drugs includc cough prcparations
with vcry small amounts of codcinc) . Also, gabapcntin and prcgabalin can
bc takcn ovcr thc longcr tcrm without losing chcctivcncss. Ior thcsc rcasons,
thcy can bc vcry hclpml fr pcrsons with prolongcd anxicty problcms that
havc no clcar prccipitant, a pattcrn that is ohcn callcd "gcncralizcd anxicty''
Thyrod Hormoncs
In scvcral scctions of this book wc'rc going to talk about thc intcrrcla-
tionships of mood and hormoncs. Thc pulsing daily rhythms of mclatonin
hom thc pincal gland that may bc involvcd with thc scasonal mood changcs
of scasonal ahcctivc disordcr [SAO) , thc mood fluctuations that can fllow
changing lcvcls of fcmalc rcproductivc hormoncs [important in undcrstand-
ing postpartum mood symptoms and prcmcnstrual syndromcs) , thc strcss
ALV A11L1LiS, HLVALiS, i1S\PP1AiS M 11,
hormoncs sccrctcd by thc adrcnal gland-all thcsc hormonal changcs sccm
to bc important in thc rcgulation of mood. 5ut pcrhaps thc most important
hormoncs in this rcspcct arc thc thyroid hormoncs.
Thc thyroid gland plays a major rolc in thc body's cncrgy rcgulation.
Too littlc thyroid gland activity lcads to sluggishncss and wcight gain, and too
much lcads to mctabolic ovcrdrivc-rapid pulsc, ncrvous cncrgy, and anxi-
cty. Whilc thc prccisc rolc of thyroid hormoncs in thc rcgulation of mood rc-
mains unclcar, it's vcry clcar that normal thyroid mnctioning is csscntial fr
chcctivc trcatmcnt of mood disordcrs. Put anothcr way, if a paticnt's mood
symptoms don`t rcspond to thc usual trcatmcnts, or i f a trcatmcnt that has
bccn chcctivc sccms to losc its chcctivcncss, a thyroid problcm, cspccially
abnormally low thyroid mnctioning [hypothyroidism) , should bc suspcctcd.
Scvcral studics havc shown that hypothyroidism is surprisingly com-
mon in paticnts with rapid- cycling bipolar disordcr.' nc group of scicntists
tcstcd fr thyroid abnormalitics in storcd blood samplcs hom almost fur
thousand paticnts who had bccn hospitalizcd fr psychiatric problcms ovcr
a pcriod of fur ycars. Thcy fund a high association bctwccn thyroid ab-
normalitics and a diagnosis of rapid- cycling bipolar disordcr. `
5ut it is also clcar that somc paticnts with bipolar disordcr whosc thy-
roid hormonc lcvcls provc to bc in thc "normal rangc whcn blood tcsts
arc donc can ncvcrthclcss bcncht hom trcatmcnt with thyroid mcdications.
Studics havc dcmonstratcd that many paticnts with bipolar dcprcssion
symptoms that arc not rcsponding to trcatmcnt havc thyroid mnction that
is "normal by thc usual critcria, but blood tcsts show thcm to bc in what
might bc callcd thc "low normal or cvcn "barcly normal rangc.' It may
bc that dcprcsscd individuals nccd a highcr lcvcl of thyroid hormoncs than
thosc who arc not dcprcsscd. Pcrhaps thc cxtra thyroid hormonc somchow
makcs thcsc paticnts morc rcsponsivc to othcr trcatmcnts. Paticnts who havc
a partial rcsponsc to lithium or othcr mood stabilizcrs may havc bcttcr con-
trol of thcir mood symptoms whcn a small dosc of thyroid rcplaccmcnt hor-
monc is addcd, cvcn if thcir thyroid hormonc lcvcls arc normal. As a papcr
on trcating rapid- cycling bipolar disordcr put it, "ormal thyroid blood
tcst rcsults] should not discouragc thc clinician hom pursuing thyroid sup-
plcmcntation`' in bipolar paticnts. `
oticc that I havcn't uscd thc tcrm |byrc|dmcd|ca||cnin this discussion.
That is bccausc it has bccn possiblc fr many ycars to synthctically producc
thc vcry samc molcculcs that thc thyroid gland itsclf naturally produccs.
[Hcncc thc brand namc, Synthroid, of thc most commonly prcscribcd brand
of lcvothyroxinc. )" What dosc of hormonc to prcscribc is dctcrmincd by
mcasuring hormonc lcvcls in thc blood, somcthing that should bc donc scv-
cral timcs a ycar fr anyonc who takcs a thyroid hormonc rcplaccmcnt.
11 M VAi
HcrhaI Prcparatons and MutrtonaI SuppIcmcnts
Thcrc arc somc nutricnts that wc must includc in our dict to rcmain
hcalthy. Thcsc arc compounds that our body cannot manufcturc but arc
ncvcrthclcss ncccssary fr normal ccllular mnctioning. Thc most fmiliar
of thcsc arc, of coursc, thc v||am|ns, compounds manufcturcd by somc
plants and animals but not by humans. Thcir namc, hom thc Latin word v||a
mcaning "lifc,' indicatcs just how important to hcalth thcy arc. Lnlcss wc cat
fods that contain thc vitamins wc nccd, scrious illncss rcsults. Scurvy, bcri-
bcri, and pcllagra arc thrcc illncsscs-now, thankfully, unfamiliar-that rc-
sult hom dchcicncics of vitamin C, vitamin 5I, and niacin, rcspcctivcly. All
thcsc illncsscs havc signihcant ccntral ncrvous systcm symptoms, cspccially
5I dchcicncy, which causcs scvcrc ccntral ncrvous systcm dcgcncration.
Thcrc arc othcr naturally occurring substanccs that our bodics arc not
vcry good at producing but that arc important fr hcalth. Thcsc arc sub-
stanccs that modcrn dicts, as opposcd to ancicnt human dicts, tcnd not to
includc in thc amounts that somc bclicvc arc ncccssary fr optimal hcalth.
A good cxamplc of thcsc substanccs is thc csscn||a|}a||y ac|ds, a collcction
of complcx ft molcculcs that arc fund in somc vcgctablcs and othcr plant
sourccs [such as flaxsccd) and in largc amounts in somc hsh. utritionists
havc long toutcd thc hcalth bcnchts of dicts rich in scafod, and thc lowcr
incidcncc of brcast canccr and hcart discasc in thc [apancsc population has
bccn attributcd to a dict rich in scafod.
Bc|an|ca|s arc plant- dcrivcd naturally occurring substanccs that havc
pharmaccutical chccts in thc body, that is, although thcy havc no nutritional
valuc, thcy intcract with somc biological systcm in thc body so as to trcat
a symptom or an illncss . A good cxamplc of this group is d|y||a||s, dcrivcd
hom thc fxglovc plant D|y||a||surura), which happcns to bc a vcry cf-
fcctivc trcatmcnt fr hcart filurc. It is thought that thc fxglovc produccs
this chcmical in its tissucs as chcmical protcction against animals and in-
sccts. Oigitalis is ftal in high doscs, but tiny amounts havc bcnchcial chccts.
Similar plant "toxins frm thc basis of many modcrn pharmaccuticals, fr
cxamplc, pain mcdications hom thc opium poppy and thc antimalaria drug
guininc hom thc bark of thc cinchona trcc.
Iinally, thcrc arc substanccs that arc normally prcscnt in thc body and
havc somc biological mnction that, takcn in largcr amounts, may cnhancc
that mnction. An cxamplc is mc|a|cn|n, a hormonc, sccrctcd by thc pincal
gland in a daily rhythm, that is important in slccp rcgulation. It also hap-
pcns to bc synthcsizcd by a varicty of plants, it is fund in thc sccds of sun-
flowcrs and coriandcrs. Although it can bc argucd that mclatonin is a truc
pharmaccutical, thc IOA tcnds to bc rcluctant to rcgulatc such naturally
occurring substanccs. Thcy arc considcrcd "nutritional supplcmcnts and arc
ALV A11L1LiS, HLVALiS, i1 S\PP1AiS M 11
rcgulatcd as fods, cvcn if, as with mclatonin, thc manufcturing proccss
takcs placc in a pharmaccutical manufcturing fcility and docsn't involvc
fod or plants or anything onc would think of as "natural'
Omcga-J Iatty Acds and Ish OI
Somc cvidcncc suggcsts that csscntial ftty acids, cspccially a subgroup
callcd cmcya-}a||y ac|ds, may bc uscml in thc trcatmcnt of mood disor-
dcrs, cspccially bipolar disordcr. Thc particular compounds thought to havc
thc most hcalth bcnchts havc tonguc-twisting namcs typical of complcx or-
ganic compounds. cicosapcntacnoic acid [LPA) and docosahcxacnoic acid
[OHA) .
umcrous studics havc indicatcd that omcga- ftty acids, takcn as hsh-
oil capsulcs, arc bcnchcial fr individuals with mood disordcrs. A rcvicw
articlc that analyzcd hvc studics in pcrsons with bipolar dcprcssion con-
cludcd that thcrc is "strong cvidcncc that bipolar dcprcssion may bc im-
provcd by thc adjunctivc usc of omcga- ' Studics of omcga- in mania havc
not shown any bcncht.
mcga- ftty acids arc incorporatcd into ccll mcmbrancs in associa-
tion with molcculcs that arc known to bc involvcd in ccll signaling. Thcy
sccm to bc activc at somc of thc samc points in ccllular signaling mccha-
nisms whcrc lithium and valproatc arc thought to work. Sincc valproatc is,
ahcr all, a syn|bc||cftty acid, thc idca that natural ftty acids might havc
bcnchts in mood disordcrs shouldn't sccm strangc at all. thcr circumstan-
tial cvidcncc has bccn citcd to support thc importancc of omcga- ftty acids
fr good mcntal hcalth. Archacological and cpidcmiological studics suggcst
that modcrn humans consumc much lcss fod that is rich in ftty acids than
ancicnt pcoplcs did and that wc may bc dchcicnt in thcsc important com-
pounds comparcd with our anccstors. This fct, combincd with cvidcncc
that thc prcvalcncc of dcprcssion is incrcasing and thc agc of onsct of mood
disordcrs i s dccrcasing, has bccn citcd as mrthcr cvidcncc of a link bctwccn
thcsc important compounds and mcntal hcalth. mcga- ftty acid thcrapy
is an adjunctivc trcatmcnt, addcd to othcr agcnts such as lithium, it should
nc|bc substitutcd fr provcn trcatmcnts. Howcvcr, givcn thc apparcnt low
risk of thcsc compounds, supplcmcntation of standard trcatmcnts fr mood
disordcrs with omcga- prcparations undcr thc supcrvision of onc's physi-
cian is an option somc paticnts will want to cxplorc.
M-AcctyI Cystcnc
Thc hcalth bcnchts of fods that arc high in an||cx|dan|sarc wcll-known.
Salcs of grccn tca, which is high in naturally occurring antioxidants, havc
120 M VAi
soarcd in rcccnt ycars, and grccn tca has bccn studicd as an adjunctivc trcat-
mcnt fr cvcrything hom diabctcs to canccr.
So just what arc antioxidants Although oxygcn is a vital ingrcdicnt fr
biological mnctioning, it is vcry rcactivc chcmically, combining with just
about anything in a rcaction callcd oxygcnation, ohcn with untoward rcsults.
Whcn oxygcn rapidly combincs with thc organic compounds in gasolinc, wc
call it "hrc' Whcn oxygcn combincs with various molcculcs in thc body, a
much lcss dramatic but still damaging proccss callcd cx|da||vcdamayc can
occur. Plants and animals all havc substanccs, thc antioxidants, that csscn-
tially prowl about scooping up thcsc damaging oxygcn- containing molc-
culcs whcn thcy occur. You can think of oxidativc strcss as a kind of bio-
logical ovcrhcating, rcguiring antioxidants t o stcp i n and cool things down.
In humans, thc main antioxidant in thc brain is a substancc callcd y|u-
|a|b|cnc, which thc body manufcturcs by combining scvcral ingrcdicnts,
including - acctyl cystcinc [AC) . High lcvcls of oxidativc strcss dcplctc
glutathionc in thc brain, but sincc glutathionc is not wcll absorbcd hom
thc gut, thc bcst way to incrcasc lcvcls is to takc in thc morc casily absorbcd
AC. Intravcnous AC is routincly uscd to halt thc oxidativc damagc to
thc livcr causcd by ovcrdoscs of acctaminophcn [Tylcnol) as wcll as in othcr
situations whcn thc antioxidants of thc body arc ovcrwhclmcd.
A placcbo- controllcd study of adjunctivc AC [that is, as an add- on to
standard mcdications such as lithium) in bipolar dcprcssion fund a sig-
nihcant bcncht, and a fllow-up study in which all thc subj ccts took AC
fr anothcr two months showcd continucd bcncht. Likc omcga- , AC is
clcarly an adjunctivc mcdication, thc bcnchts of which should bc considcrcd
promising rathcr than hrmly cstablishcd. cvcrthclcss, it is an option somc
may wish to cxplorc-again, with thc guidancc of thcir physician.
St. John' s Wort
Hycr|cumcr}cra|um, commonly known as St. [ohn's wort, is onc of
about thrcc hundrcd spccics of shrubby pcrcnnial plants [of gcnus Hycr-
|cum)with bright ycllow flowcrs , thc plants grow in most of thc tcmpcratc
rcgions of thc world. Tcas and othcr cxtracts of St. [ohn`s wort havc bccn rcc-
ommcndcd by hcrbalists fr ccnturics to trcat cvcrything hom insomnia to
thc painml viral skin infcction callcd shinglcs. In thc latc I8os hypcricum}cra|um)was invcstigatcd as a possiblc trcatmcnt fr HIV infcction
whcn it was fund to havc activity against rctroviruscs, but its activity un-
frtunatcly did not translatc into clinical uscmlncss against HIV infcction.
A I6 articlc in thc Br|||sbMcd|ca|)curna|that systcmatically rcvicwcd
twcnty- thrcc dihcrcnt studics involving a total of I,;y; paticnts concludcd
that "cxtracts ofhypcricum arc morc chcctivc than placcbo fr thc trcatmcnt
ALV A11L1LiS, HLVALiS, i1S\PP1AiS M 121
of mild to modcratcly scvcrc dcprcssivc disordcrs' ' Morc rcccnt studics
havc bccn lcss cncouraging. Whcn St. [ohn`s wort was comparcd with a pla-
ccbo in two hundrcd paticnts who had bccn rigorously cvaluatcd and diag-
noscd with major dcprcssion, thc hcrbal prcparation was no bcttcr than thc
placcbo in trcating dcprcssion. This study concludcd that "thc rcsults do not
support signihcant antidcprcssant or anti- anxicty chccts fr St. [ohn`s wort
whcn comparcd to placcbo in a clinical samplc of dcprcsscd paticnts and
that "pcrsons with major dcprcssion should not bc trcatcd with St. [ohn's
wort, givcn thc morbidity and mortality risks of untrcatcd or inchcctivcly
trcatcd major dcprcssion' '" In a fllow- up study, thc samc rcscarchcrs rc-
portcd that whcn thc individuals who had not rcspondcd to St. [ohn's wort
wcrc givcn standard antidcprcssants, most of thcm improvcd, suggcsting
that thc hcrbal prcparation had filcd not bccausc thcsc wcrc "trcatmcnt-
rcsistant paticnts but simply bccausc St. [ohn's wort wasn't chcctivc against
thcir dcprcssion.
Qucstions about thc chcctivcncss of St. [ohn's wort arc onc thing, but
rcports of it making things worsc arc unfrtunatcly not hard to hnd.
A y-ycar-old man without prior psychiatric trcatmcnt prcscntcd to
our clinic with dcprcssion. His history was signihcant fr hypomania
cycling into dcprcssion cvcry [unc and Occcmbcr fr zo ycars, consis-
tcnt with a diagnosis of bipolar II disordcr . . . . f notc, his I8-ycar- old
son is trcatcd fr bipolar I disordcr with lithium. Hc had no mcdical
history and had ncvcr bccn prcscribcd psychotropics, although in May
I8, hc bought a bottlc of St. [ohn`s wort with thc hopc that it could
improvc his mood.
Shortly ahcr taking St. [ohn`s wort oo mg/day, hc noticcd a surgc
in sclf- cstccm. His thoughts raccd, hc was morc talkativc, his slccp
dccrcascd, his scx drivc incrcascd, hc spcnt moncy cxccssivcly, and
hc drovc fstcr than usual. Two months latcr, his bchavior changcd
dramatically. Hc misscd work bccausc hc just "didn`t carc,' hc angrily
lashcd out at his wifc, hc shoplihcd hom thc supcrmarkct, and hc
surfcd thc Intcrnct fr romantic intriguc. Hc communicatcd with
many womcn by c-mail, latcr mct thcsc womcn, and cngagcd in
unprotcctcd scxual rclationships with as many as fur womcn in 1
wcck. Hc rcgardcd thcsc ahairs as a "hobby,' lacking any apprcciation
fr thcir impact on his marriagc. Hc had visual illusions and bclicvcd
that pcoplc at work wcrc trying to undcrminc him. Although hc had
cxpcricnccd mood clcvations in thc past, hc cxplaincd that this cpi-
sodc was particularly long and scvcrc and admits that hc was doing
things which "didn't makc scnsc'
Subscgucntly, hc rcduccd his S[W to oo mg/day, and his dcprcs-
122 M VAi
sion rccurrcd. His trcatmcnt tcam discontinucd thc S[W and initiatcd
lithium and] hc rcports stcady improvcmcnt in mood. ' '
I think it's fir to say that St. [ohn`s wort isn`t good cnough as an antidcprcs-
sant to hclp pcrsons with bipolar disordcr, but that it's cnough of an anti-
dcprcssant to causc problcms fr thcm, and so is bcst lch alonc, cxccpt pcr-
haps in thc gardcn.
ALV A11L1LiS, HLVALiS, i1S\PP1AiS M 12j
L M A 1 H
1d1D-11HU1d11OD 1Od1HOD1S
|rca|mcn|s, you'rc not alonc. It's a rclativcly ncw tcrm fr a varicty of trcat-
mcnt tcchnigucs, onc of which has bccn around fr many dccadcs. Thcsc
tcchnigucs involvc using tiny clcctrical impulscs to stimulatc arcas of thc
brain. Thc oldcst of thcsc is clcctro convulsivc thcrapy, in which a vcry small
clcctrical currcnt is applicd dircctly to thc scalp whilc thc paticnt is undcr
gcncral ancsthcsia. Somc ncwcr tcchnigucs usc cvcn smallcr clcctrical im-
pulscs and rcguirc no ancsthcsia. Thc dctails of how thcsc trcatmcnts work is
still fr hom ccrtain. Howcvcr, it is firly clcar that thcy all work by ahccting
thc lcvcls of clcctrical activity in ccrtain arcas of thc brain, arcas that arc
undcractivc or ovcractivc during cpisodcs of abnormal mood. Thcy bring
activity lcvcls into a morc normal balancc, in much thc samc way that vcry
small clcctrical impulscs arc uscd to rcrcgulatc hcart rhythms in individuals
who havc a cardiac paccmakcr.
EIcctroconvuIsvc Thcrapy
Although thc chcctivcncss of clcctroconvulsivc thcrapy [LCT) in mood
disordcrs was not a complctcly accidcntal discovcry, its original thcorcti-
cal basis has bccn shown to havc no validity, so thc dcvclopmcnt of mod-
crn LCT, likc so many othcr trcatmcnts in psychiatry, was a kind of happy
accidcnt. In thc carly Ios thc Hungarian physician [oscph Ladislas von
Mcduna proposcd that thcrc was a mutual antagonism bctwccn cpilcpsy
and schizophrcnia. paticnts who suhcrcd hom cpilcpsy did not suhcr hom
schizophrcnia and vicc vcrsa. Modcrn rcscarch has shown that this is not
thc casc, but von Mcduna was convinccd of thc truth of this asscrtion on
thc basis of his microscopic post- mortcm cxamination of thc brains of pcr-
sons with thc two conditions. Hc conductcd animal cxpcrimcnts attcmpting
to hnd a way to producc scizurc activity artihcially. In Iy hc publishcd a
papcr rcporting a dramatic improvcmcnt in symptoms ahcr artihcially in-
ducing scizurcs in scvcral paticnts who suhcrcd hom what hc thought to
bc schizophrcnia [in rctrospcct, it's probablc that at lcast somc of thcm had
scvcrc mood disordcrs with psychotic symptoms ) . Von Mcduna uscd in-
j cctions to producc scizurcs, but scvcral ycars latcr two Italian psychiatrists
rcportcd that scizurcs could bc produccd by bricfly passing a low-voltagc
clcctrical currcnt through thc skull by mcans of clcctrodcs applicd to thc
scalp. Lgo Ccrlctti and Lucio 5ini hrst dcvclopcd thcir tcchniguc in animals
and thcn tricd it on scvcral paticnts with "schizophrcnia,' and thcy also rc-
portcd rcmarkablc succcss.
Although paticnts with somc frms of truc schizophrcnia do indccd
ohcn show improvcmcnt in somc of thcir symptoms ahcr thcsc trcatmcnts,
it guickly bccamc apparcnt that it was thc scvcrcly dcprcsscd paticnts who
showcd improvcmcnt-improvcmcnt that was littlc short of miraculous.
Occadcs prcviously, Lmil Kracpclin had dcscribcd paticnts in a catatonic
statc hom dcprcssion. " Thc paticnts lic in bcd taking no intcrcst in anything.
Thcy bctray no pronounccd cmotion, thcy arc mutc, inacccssiblc, thcy pass
thcir bowcl movcmcnts] undcr thcm, thcy starc straight in hont of thcm
with a] vacant cxprcssion of countcnancc likc a mask and with widc opcn
cycs' ' In thc I(os, ahcr rccciving "clcctroshock trcatmcnts, such paticnts
had complctc rccovcry hom thcir symptoms within a mattcr of days. Thc
most rcccnt maj or brcakthrough in thc trcatmcnt of psychiatric problcms-
thc discovcry of thc Wasscrmann tcst fr syphilis in Io6-now sccmcd al-
most insignihcant comparcd with this astonishing ncw thcrapcutic tcch-
niguc. aturally, intcrcst in LCT sprcad guickly around thc globc.
5ut LCT's succcss was also ncarly its downfll. Likc many othcr sccm-
ingly miraculous trcatmcnts, it was ovcrprcscribcd at hrst and probably was
administcrcd to many hundrcds of pcrsons it had littlc chancc of hclping.
It's important to rcmcmbcr, howcvcr, that thosc wcrc dcspcratc timcs in psy-
chiatry. With thc discovcry of antipsychotic mcdications ncarly a dccadc
oh and thc discovcry of antidcprcssants ncarly two dccadcs in thc mturc,
"littlc chancc of hclping was bcttcr than no chancc at all. Sincc, as wc shall
scc, LCT is a highly chcctivc trcatmcnt fr mania, somc institutions wcrc
inclincd to usc it fr any highly agitatcd paticnts and somctimcs on mcrcly
uncoopcrativc oncs [a misusc that was dramatizcd-with a fcw inaccuracics
unfrtunatcly thrown in-in thc hlm OncI|cwcvcr|bcCuc/ccsNcs|) .An-
V1i~S1A\11Li VAiS M 12j
othcr ncgativc fctor was that in thc hrst dccadc or so ahcr its dcvclopmcnt,
LCT could havc somc vcry scrious complications. An cpilcptic scizurc is a
violcnt cvcnt. all thc musclcs of thc body contract simultancously fr a fcw
momcnts, somctimcs with such frcc that brokcn boncs rcsult. 5rcathing
stops as wcll, and hcart- rhythm irrcgularitics can occur.
Thc ncarly indiscriminatc ovcrprcscription of a thcrapy with scrious po-
tcntial sidc chccts l cd to a backlash. 5y thc latc I6os and I;os, although
modcrn ancsthctic tcchnigucs wcrc making LCT safcr, and morc carcml rc-
scarch was bcing donc to dctcrminc which psychiatric disordcrs thc trcat-
mcnt hclpcd with and which it did not, thc damagc to LCT's rcputation
had alrcady bccn donc. Cuc/ccsNcs|, awardcd thc scar fr bcst movic in
I;y, dcpictcd LCT as it would havc bccn administcrcd circa I(y and ccr-
tainly didn`t hclp. ) Statc hospitals drcw up rcgulations sharply curtailing its
usc, and lcgislation was in chcct bricfly in Califrnia banning thc proccdurc
Iortunatcly, thc pcndulum has swung back to ccntcr. LCT is now safcr
than most surgical proccdurcs, sidc chccts arc minimal, and guidclincs fr
whcn it should bc uscd havc bccn clarihcd. A I8o survcy of I66 LCT pa-
ticnts rcportcd that about half of thcm thought a trip to thc dcntist was morc
unplcasant than an clcctroconvulsivc trcatmcnt.'
Improvcmcnts in LCT havc bccn duc both to changcs in thc way thc
clcctrical stimulus is uscd and, pcrhaps cvcn morc, to modcrn ancsthcsia.
Many psychiatric hospitals havc trcatmcnt suitcs fr LCT, in gcncral hospi-
tals, LCT is ohcn administcrcd in thc rccovcry room of thc hospital's sur-
gical suitc [thc arca whcrc paticnts waking up hom surgcry arc takcn fr
obscrvation) . Thc LCT trcatmcnt lasts only about sixty scconds, most of thc
"trcatmcnt timc is thc tcn minutcs or so it takcs to administcr gcncral an-
csthcsia bcfrc thc actual trcatmcnt and anothcr tcn minutcs fr thc paticnt
to awakcn hom it.
Thc crucial ancsthctic advancc fr LCT was thc introduction in thc Iyos
of agcnts callcd musc|crc|axan|s, or morc propcrly ncurcmuscu|ar||cc/|ny
aycn|s, which tcmporarily paralyzc thc paticnt by blocking ncrvc hbcr sig-
nals to thc musclcs. Thcsc mcdications prcvcnt thc violcnt musclc contrac-
tions during scizurcs that charactcrizcd carly LCT usc.
Ahcr an intravcnous mcdication is givcn to put thc paticnt to slccp, thc
ncuromuscular blocking agcnt is givcn so that thc paticnt's musclcs arc al-
most complctcly rclaxcd. Llcctrodc disks similar to thosc uscd fr cardiac
dchbrillation arc applicd to thc scalp. Modcrn LCT cguipmcnt dcsigncd fr
thc purposc dclivcrs a prcciscly timcd and mcasurcd clcctrical stimulus . In
|||a|cra| trcatmcnts, an clcctrodc is applicd ovcr cach tcmplc. In un||a|cra|
12 M VAi
trcatmcnts, whcrcin thc objcct is to stimulatc only half of thc brain, onc
clcctrodc is placcd in thc middlc of thc frchcad or thc crown of thc hcad
and thc othcr at thc tcmplc. [Lnilatcral trcatmcnt causcs lcss post-LCT con-
msion and mcmory problcms and is now uscd almost cxclusivcly, although
paticnts fr whom unilatcral trcatmcnts arc inchcctivc ohcn switch to rc-
cciving bilatcral trcatmcnts. )
Thc clcctrical stimulus is applicd fr two to cight scconds, triggcring
scizurc activity in thc brain. Thc "scizurc in modcrn LCT is prctty much an
clcctrical cvcnt only, with fcw or no j crking movcmcnts such as thosc that
usually charactcrizc scizurcs, and thus what LCT causcs is usually callcd a
modihcd scizurc. Thc LCT cguipmcnt also rccords an clcctrocnccphalogram
[a mcasurcmcnt of thc clcctrical activity of thc brain), allowing thc physi-
cian to monitor thc scizurc activity, which usually lasts lcss than a minutc.
Thcrc might bc somc musclc contractions obscrvcd during this timc, but thc
musclc rclaxant kccps thc paticnt ncarly motionlcss. Lsually a guickcning
of thc hcart ratc and an incrcasc of blood prcssurc occur, which also signal
that thc "scizurc has occurrcd. Thc ancsthctist uscs a fcc- mask brcathing
dcvicc to dclivcr oxygcn until thc paticnt wakcs up hvc or tcn minutcs latcr,
and thc trcatmcnt is ovcr. As with othcr short proccdurcs donc undcr gcn-
cral ancsthcsia, thc hrst words thc paticnt usually says upon awakcning in
thc rccovcry arca arc, "Whcn will I havc my trcatmcnt That is, paticnts
havc no mcmory of thc proccdurc.
About thc only paticnts who absolutcly must not rcccivc LCT arc thc
fcw individuals with mcdical conditions so scvcrc that cvcn tcn to hhccn
minutcs of gcncral ancsthcsia is too dangcrous-pcoplc with scvcrc cardiac
or lung discascs, fr cxamplc. LCT is safc in cldcrly pcrsons and during
Paticnts awakcning hom ancsthcsia ahcr LCT arc a bit groggy, of coursc,
and many arc also slightly mzzy- hcadcd and fccl "spaccy fr anothcr hour
or so. This chcct is probably rclatcd to thc trcatmcnts thcmsclvcs, not just
thc ancsthcsia, and it rcscmblcs thc mild postscizurc conmsion that paticnts
with truc cpilcpsy ohcn cxpcricncc. ccasionally a morc prolongcd pcriod
of conmsion callcd dc||r|umis sccn, cspccially ahcr bilatcral trcatmcnts and
cspccially toward thc cnd of a coursc of trcatmcnts. Scdativcs can trcat this
problcm, but whcn it occurs, considcration should bc givcn to stopping thc
trcatmcnts or giving thcm lcss ohcn.
Thc most troublcsomc possiblc sidc chccts of LCT rclatc to its chcct on
mcmory. about two-thirds of paticnts rcport that LCT ahccts thcir mcmory,
at lcast tcmporarily. Thc most common mcmory problcm is with v|suc-sa-
||a|mcmory, thc typc nccdcd to gct placcs and hnd things. In a fmous arti-
clc in thc Br|||sb)curna|c}Psycb|a|ry, a practicing psychiatrist who rcccivcd
a coursc of LCT to trcat dcprcssion wrotc of his cxpcricnccs and notcd that
V1i~S1A\11Li VAiS M 12,
ahcr his coursc of trcatmcnts, hc could no longcr rcmcmbcr how to gct
whcrc hc nccdcd to go using thc London Lndcrground [thc subway) . ' Hc
suddcnly fund that hc had frgottcn whcrc thc dihcrcnt lincs wcnt and
nccdcd to consult routc maps cvcn fr routinc trips that hc had takcn fr
ycars. Ahcr a timc, cvcrything bccamc fmiliar again, and hc was knowl-
cdgcablc cnough about what was going on to hnd thc wholc thing amusing
rathcr than worrisomc [ or at lcast that's what hc wrotc in thc articlc) . If pa-
ticnts arc not prcparcd to cxpcct this possiblc sidc chcct, thcy can bc guitc
alarmcd whcn thcy rcturn homc and hnd thcir housc oddly unfmiliar or
hnd that thcy can't put thcir hands on thcir fvoritc hying pan or rcmcmbcr
whcrc in thc world thosc darn hcdgc- clippcrs arc. Thc cxpcricncc of thc
Lnglish psychiatrist is a rcmindcr that bcing frcwarncd and prcparcd fr
thcsc potcntial problcms is important so that if and whcn thcy occur, thcy
arc not so hightcning.
Anothcr typc of mcmory loss somctimcs sccn with LCT ahccts thc mcm-
ory of cvcnts occurring during thc scvcral wccks whcn thc paticnt was rc-
cciving LCT. Sincc trcatmcnts arc typically givcn thrcc timcs a wcck and
a paticnt usually nccds six to twclvc trcatmcnts fr complctc rccovcry, a
coursc of LCT will last two to fur wccks. Paticnts not inhcgucntly losc thc
mcmory of somc cvcnts that occurrcd during thosc wccks. Paticnts somc-
timcs also suhcr rc|rcyradc amncs|a as wcll. mcmory loss fr a pcriod of
timc bcfrc thcy actually startcd LCT. This is thought to occur bccausc LCT
somchow disrupts thc proccss by which shortcr- tcrm mcmorics bccomc in-
corporatcd into longcr- tcrm mcmory. [ If you'vc cvcr lost an hour's worth
of computcr work bccausc you filcd to savc your work bcfrc somcthing
untoward "hozc your computcr, you gct thc idca of what rctrogradc amnc-
sia is. Thc short-tcrm mcmorics that arc still in thc brain's mcmory "buhcr
arc lost bccausc of thc LCT. ) Paticnts who havc succcssmlly complctcd a
coursc of LCT may say thcy don't rcmcmbcr chccking in to thc hospital, or
thcy might not rccollcct a homc visit or a trip thcy took with thcir fmily
during thc trcatmcnts . This problcm sccms to bc worst just ahcr a paticnt
rcccivcs LCT. In a study of frty- thrcc paticnts who wcrc intcrvicwcd about
thcir mcmory a fcw wccks ahcr complcting LCT, somc rcportcd dimculty
rcmcmbcring cvcnts fr a pcriod up to two ycars bcfrc thcir LCT. 5ut whcn
thcsc paticnts wcrc tcstcd again scvcn mcn|bsahcr thcir trcatmcnt, thc morc
distant mcmorics had bccn almost complctcly rccovcrcd. '
As you might suspcct, thcsc kinds of mcmory problcms arc almost im-
possiblc to pick up on tcsts, and so dcspitc many ycars of mcmory rcscarch
on LCT paticnts, it has bccn dimcult to guanti prcciscly thc chcct of LCT
on long- tcrm mcmorics. Anothcr fctor that conmscs thc issuc is thc chcct
that scvcrc dcprcssion has on mcmory. Scvcral studics indicatc that com-
12 M VAi
plaints of mcmory problcms ahcr LCT corrclatc bcttcr with thc scvcrity of
thc paticnt's dcprcssion than with how thcy do on mcmory tcsts. `
Llcctroconvulsivc thcrapy can bc thought of as a symptomatic trcat-
mcnt fr both phascs of bipolar disordcr. although it can guickly intcrrupt
an cpisodc of dcprcssion or mania, it docs not havc a long-tcrm chcct as a
mood stabilizcr [a sym|cma||c trcatmcnt trcats sym|cmsbut not thc un-
dcrlying discasc) . Mcdication trcatmcnt will still bc ncccssary to sustain thc
bcncht of LCT and to kccp thc paticnt's mood statc stablc ahcr thc trcat-
mcnts arc hnishcd.
Typically, whcn thc dccision is madc to givc a coursc of LCT, mcdica-
tions arc stoppcd or thcir doscs rcduccd. [ Scdativc mcdications ohcn shortcn
and othcrwisc intcrfcrc with thc LCT "scizurc,' and so do thc anticonvulsant
mood stabilizcrs-thcy arc anticonvulsants, ahcr all. Lithium sccms to makc
paticnts morc pronc to cpisodcs of conmsion ahcr thcir trcatmcnts. )
LCT is gcncrally considcrcd to bc thc most chcctivc antidcprcssant trcat-
mcnt availablc. aturally, it should bc a trcatmcnt considcration whcncvcr
a bipolar paticnt continucs to bc scvcrcly dcprcsscd dcspitc antidcprcssant
mcdication trcatmcnt. It is also ra|d|y chcctivc. hcn, paticnts arc dra-
matically improvcd ahcr just thrcc or fur trcatmcnts-that is, ahcr hvc to
scvcn days . Scvcrcly suicidal paticnts or thosc who havc stoppcd cating and
drinking and arc in dangcr of malnutrition and dchydration-any paticnts
fr whom profund dcprcssion has bccomc an immincntly lifc- thrcatcning
illncss-arc candidatcs fr LCT. Prcgnancy is also considcrcd to bc an in-
dication fr usc of LCT to trcat bipolar dcprcssion bccausc of thc risk most
mood- stabilizing mcdications posc to thc fctus. " 5ccausc dcprcssion can bc
highly rcsistant to antidcprcssant mcdications and also ris| in somc cldcrly
paticnts, LCT is hcgucntly rccommcndcd as a hrst- linc trcatmcnt fr scvcrc
dcprcssion in oldcr pcoplc as wcll. Ocprcsscd bipolar paticnts who rcccivc
LCT can bccomc slightly hypomanic. Whcn this occurs, obviously it's timc
to stop thc trcatmcnts. Lnlikc thc antidcprcssants, LCT docs not sccm to
incrcasc thc cycling of thc illncss.
LCT is also a highly chcctivc trcatmcnt fr mania. A Iq rcvicw of
hhy ycars' cxpcricncc of thc usc of LCT fr trcating mania fund that it
providcd complctc symptom rcmission or markcd improvcmcnt in 8o pcr-
ccnt of thc manic paticnts studicd. Many of thc paticnts in thcsc studics had
filcd to rcspond to many othcr availablc trcatmcnts-making this succcss
ratc all thc morc imprcssivc. LCT sccms to work morc guickly in mania
than in dcprcssion. nc study fund that paticnts rccovcrcd ahcr an avcr-
agc of six trcatmcnts, about half thc usual rcguircmcnt fr thc trcatmcnt of
V1i~S1A\11Li VAiS M 12
dcprcssion. ' Scvcrcly manic paticnts whosc highly agitatcd statc bccomcs
physically dangcrous arc obvious candidatcs fr LCT, as arc prcgnant manic
LCT is a valuablc thcrapcutic tool fr any bipolar paticnt who is vcry
sick and sccms to bc gctting sickcr dcspitc aggrcssivc trcatmcnt with mcdi-
cation. It is pcrhaps thc most chcctivc trcatmcnt thcrc is fr scvcrc dcprcs-
sion and scvcrc mania, and it ohcn works morc guickly than mcdications. '"
If you'rc bcginning to wondcr why LCT isn`t uscd morc ohcn in bipolar dis-
ordcr, you'rc in vcry good company. It is ccrtainly much morc complicatcd
to go through gcncral ancsthcsia two or thrcc timcs a wcck fr two to fur
wccks than it is to takc mcdication, but LCT may wcll still bc undcrutilizcd,
cspccially fr paticnts sick cnough to nccd hospitalization. Wc also know
that bipolar dcprcssion can bc lcss rcsponsivc to mcdication trcatmcnt, and
thcrc is thc risk of antidcprcssants accclcrating thc cycling of bipolar illncss.
Thcsc fcts makc thc usc of LCT fr scvcrc bipolar dcprcssion cvcn morc
TranscranaI Magnctc StmuIaton
Transcranial magnctic stimulation [TMS) is a ncw thcrapcutic tcch-
niguc similar to LCT that is chcctivc in trcating mood disordcrs. Thc grcat
advantagc of TMS ovcr LCT is that TMS is much simplcr to administcr . no
scizurc activity is induccd by thc trcatmcnt, and thcrcfrc no ancsthcsia is
This novcl tcchniguc takcs advantagc of a principlc of clcctromagnctism
callcd |nduc||cnto dclivcr an clcctrical stimulus to thc brain without apply-
ing clcctrical cncrgy to thc scalp [as in LCT) . Ouring TMS trcatmcnts, a
magnctic coil is hcld against thc scalp, and thc magnctic hcld that dcvclops
in thc coil causcs clcctrical currcnt to flow through ncarby ncurons within
thc skull. o clcctricity passcs through thc skull, as in LCT, rathcr, thc mag-
nctic hcld "induccs a tiny clcctrical currcnt in thc undcrlying brain tissuc.
Sincc thc clcctrical currcnt that is gcncratcd in thc brain tissuc by TMS is
vcry small, no scizurc occurs, thus, no ancsthcsia is nccdcd. Pulscs of mag-
nctic cncrgy arc dclivcrcd ovcr a pcriod of about twcnty to frty minutcs
whilc thc paticnt simply sits in a chair, awakc and alcrt throughout thc wholc
proccdurc. thcr than somc sorcncss hom musclc stimulation, thcrc appcar
to bc no sidc chccts of any kind. ' '
TMS has bccn uscd fr ycars t o do brain mapping. Thc mapping of
motor arcas of thc brain involvcs stimulating an arca and thcn mcasuring
clcctrical activity in thc musclcs controllcd by that arca. Stimulating a scn-
sory arca of thc brain can causc a pcrson to fccl tingling in thc part of thc
body that scnds scnsory ncrvcs to that arca. Sophisticatcd TMS tcchnigucs
1j0 M VAi
arc also bcing uscd to study languagc mnctions and thc organization of
complcx movcmcnts as wcll.
It is possiblc to givc a placcbo TMS trcatmcnt, fcilitating valid rcscarch
on thc cmcacy of TMS in dcprcssion. [A truc placcbo- controllcd study of
LCT would rcguirc giving two groups of paticnts ancsthcsia but giving thc
clcctrical stimulus only to paticnts in onc of thc groups. Risking ancsthcsia
to rcccivc a fkc LCT trcatmcnt is somcthing fcw pcoplc would voluntccr
fr, and cthically it is a rathcr dubious idca. ) Whcn thc TMS coil is applicd
to thc scalp at a slightly dihcrcnt anglc hom that normally uscd to givc trcat-
mcnts, it docs not causc clcctrical currcnt to flow through thc brain tissuc
and thus docs not havc thc usual TMS chcct. Howcvcr, bccausc stimulation
of thc musclcs still occurs, thc slight musclc sorcncss associatcd with thc
trcatmcnt occurs as wcll, and so rcscarch subj ccts havc no way of knowing
whcthcr thcy arc gctting a sham trcatmcnt or thc rcal thing. This makcs thc
all- important doublc-blind placcbo- controllcd studics firly casy to do.
As wc shall scc in chaptcr i8, various studics indicatc that thc lch prc-
hontal lobcs of thc brain arc lcss activc than normal in dcprcssion. This
hnding has lcd rcscarchcrs to try TMS trcatmcnts on dcprcsscd paticnts by
stimulating thc lch prchontal lobcs. nc of thc hrst studics on TMS in thc
trcatmcnt of dcprcssion appcarcd in thc Amcr|can)curna|c}Psycb|a| in

In this study hom thc ational Institutc of Mcntal Hcalth, twclvc

paticnts rcccivcd TMS stimulations ovcr a pcriod of twcnty minutcs cvcry
wcckday fr two wccks. Lithcr bcfrc or ahcr thc two wccks of thcrapy, thc
paticnts wcrc givcn two wccks of "sham`' trcatmcnts [thc placcbo) , during
which thc TMS coil was hcld at an anglc that would not causc brain tissuc
stimulation. Thc paticnts wcrc tcstcd fr dcprcssivc symptoms by traincd
invcstigators, using a standardizcd gucstionnairc. cithcr thc paticnts nor
thc invcstigators giving thc mood gucstionnairc kncw whcthcr thc paticnts
wcrc rccciving rcal or sham TMS [making thc study dcu||cblind) . Thcrc
was a statistically signihcant mood improvcmcnt in thcsc paticnts ahcr thc
rcal TMS trcatmcnts, but not ahcr thc sham trcatmcnts . Scvcral paticnts
continucd TMS ahcr thc complction of thc study and cxpcricnccd mrthcr
clinical improvcmcnt in thcir dcprcssivc symptoms. In scvcral studics, dc-
prcsscd paticnts with drug- rcsistant dcprcssion havc shown improvcmcnt
ahcr TMS. ' '
TMS i s i n its infncy. Thc strcngth of thc magnctic stimulation that is
most bcnchcial, thc cxact placcmcnt of thc coil, thc numbcr of magnctic im-
pulscs dclivcrcd pcr trcatmcnt scssion, thc total numbcr of trcatmcnts, and
thc duration of thcrapy arc all undcr invcstigation at various ccntcrs around
thc world. Will TMS, likc LCT, bc chcctivc in bipolar dcprcssion as wcll as in
unipolar dcprcssion How about in mania Thcsc and many othcr gucstions
rcmain to bc answcrcd. It is clcar, howcvcr, that TMS is a vcry promising
V1i~S1A\11Li VAiS M 1j1
dcvclopmcnt in thc trcatmcnt of mood disordcrs and may opcn up a wholc
ncw array of trcatmcnt options.
Vaga Mcrvc StmuIaton
Vagal ncrvc stimulation [VS) is anothcr ncw approach fr trcating dc-
prcssion that has now bccn approvcd by thc IOA.
Thc vagal ncrvc [or vayus) is a long ncrvc that cmcrgcs hom thc basc
of thc brain and travcls down thc ncck and into thc chcst and abdomcn. It
rcgulatcs somc vital bodily mnctions such as digcstion and hcart ratc. Its
conncctions in thc brain occur through important ccntcrs thought to bc
involvcd with cmotional rcgulation and spccihcally with mood rcgulation.
VS is donc by mcans of a paccmakcr- likc dcvicc that must bc surgically
implantcd, it is conncctcd to thc vagus ncrvc and constantly dclivcrs tiny
clcctrical signals. Thc conncction is madc whcrc thc ncrvc travcls through
thc ncck, making it a simplc surgical proccdurc that is usually donc on an
outpaticnt basis.
Animal studics donc as carly as thc I os dcmonstratcd that clcctrical
stimulation of thc vagal ncrvc produccd changcs in thc clcctrical activity of
thc brain, and studics in thc I8os dcmonstratcd that VS could control
cpilcptic scizurcs in dogs.
In thc Ios VS bccamc availablc fr thc trcatmcnt of intractablc cp-
ilcpsy in humans, hrst in Luropc and thcn in thc Lnitcd Statcs. 5y thc cnd
of zooo, about six thousand paticnts worldwidc had rcccivcd VS, almost
all of thcm fr thc trcatmcnt of cpilcpsy. As with anti-cpilcptic mcdications
that latcr turncd out to bc chcctivc mood stabilizcrs, VS was notcd to havc
bcnchcial chccts on mood in scvcral paticnts who had rcccivcd it to trcat
thcir scizurcs. Somc had substantial antidcprcssant chccts hom VS, cvcn
though thc trcatmcnt didn`t improvc thcir scizurc control.
In onc of thc hrst studics of thc VS trcatmcnt of dcprcssion, thirty
adults rcccivcd VS fr scvcrc trcatmcnt- rcsistant dcprcssion, ninc of thc
paticnts had a diagnosis of bipolar I or bipolar II disordcr. Somc of thcsc pa-
ticnts had takcn dozcns of dihcrcnt mcdications and undcrgonc LCT, with
littlc bcncht. About half of thc paticnts bcnchtcd hom VS. '' In a fllow- up
study, most of thc paticnts who had shown a rcsponsc wcrc continuing to do
wcll, and scvcral wcrc fund to havc cxpcricnccd continucd improvcmcnt
whcn thcy wcrc cvaluatcd ahcr onc ycar of VS trcatmcnt. ' `
Emcrgng TcchnoIogcs
Scvcral othcr mcthods of dclivcring small clcctrical stimuli to arcas of
thc brain arc bcing invcstigatcd as possiblc trcatmcnts fr mood disordcrs.
1j2 M VAi
nc of thcsc is dcc|ra|ns||mu|a||cn[ O5S) , a tcchniguc that has bccn uscd
sincc thc mid- Ios to trcat Parkinson`s discasc, trcmor, chronic pain, and
othcr ncurological conditions. Likc vagal ncrvc stimulation, O5S uscs clcc-
trodcs powcrcd by a paccmakcr- likc dcvicc in thc chcst wall. Lnlikc VS,
howcvcr, thc clcctrodcs arc implantcd dircctly into dccp brain ccntcrs. A
vcry invasivc ncurosurgical proccdurc is rcguircd, and so O5S has bccn in-
vcstigatcd in only a small numbcr of paticnts with thc most trcatmcnt-rcsis-
tant mood disordcrs, including somc with bipolar disordcr, but thc rcsults
havc bccn vcry promising.
Anothcr invcstigational trcatmcnt is |ranscran|a| d|rcc| currcn|s||mu-
|a||cn [tOCS) , i n which a small clcctrical currcnt i s dclivcrcd ovcr a pcriod
of timc by mcans of clcctrodcs applicd to thc surfcc of thc scalp. This tcch-
niguc rcscmblcs clcctroconvulsivc thcrapy in that an clcctrical currcnt is
passcd dircctly through thc skull, but thc currcnt is much smallcr. Whcrcas
thc currcnt dclivcrcd by an LCT dcvicc is usually 8oo mA, tOCS dcviccs
dclivcr only 2 mA. As with transcranial magnctic stimulation, thc paticnt
can rcmain awakc, simply sitting in a chair, during thc trcatmcnts, and no
ancsthcsia is rcguircd. Thcsc trcatmcnts, likc TMS, last about twcnty min-
utcs and arc rcpcatcd daily fr scvcral wccks. A big advantagc of tOCS ovcr
TMS is that thc cguipmcnt is much simplcr and hcncc lcss cxpcnsivc. Scv-
cral sham- controllcd clinical trials of tOCS havc bccn publishcd, and thc
rcsults havc bccn vcry cncouraging.
V1i~S1A\11Li VAiS M 1jj
L M A P 1 H
arc thc fundation of thc trcatmcnt of bipolar disordcr, counscling and
psychothcrapy arc important, pcrhaps indispcnsablc, additional thcrapcutic
intcrvcntions. Somc pcoplc still picturc psychothcrapy as somcthing that
happcns in a richly panclcd, dimly lit omcc whcrc a bcardcd psychiatrist
sits taking notcs in a high-backcd lcathcr chair bchind a paticnt lying on
a couch who is trying to rcmcmbcr what shc drcamcd about last night. r
pcrhaps thcy think of talk- radio thcrapists, dispcnsing sound-bitc-sizcd ad-
vicc to thc lovclorn and loncly bctwccn car commcrcials on thc AM dial.
All of this is psychothcrapy of a sort, but thc practicc of psychothcrapy is a
scrious and wcll- studicd clinical intcrvcntion fr individuals in psycholog-
ical distrcss that rcguircs ycars of training and cxpcricncc to mastcr. Many
typcs of counscling and thcrapy arc cnormously hclpml in bipolar disordcr.
5y rcading this book to this point, you'vc alrcady rcccivcd scvcral hours of a
kind of thcrapy. You'vc allowcd an obj cctivc but sympathctic individual with
knowlcdgc and cxpcricncc about mcntal illncss and psychological proccsscs
[that's mc) to prcscnt fcts about bipolar disordcr to incrcasc your undcr-
standing of thc illncss. This undcrstanding has, I hopc, hclpcd you makc
scnsc of your thoughts and fcclings about this problcm as it ahccts you. It
has also, pcrhaps, hclpcd prcparc you to makc dccisions bascd on knowl-
cdgc rathcr than on cmotions such as fcar of or angcr about thc illncss. This
is, in largc mcasurc, what thcrapy is all about. not intcrprcting drcams, not
simply doling out advicc, and ccrtainly not supplying all thc answcrs, but
providing good infrmation, objcctivc fccdback, and solid cncouragcmcnt
in a supportivc, conhdcntial sctting.
Bran and Mnd
In chaptcr q I dcscribcd how manic- dcprcssivc illncss camc to bc callcd
a "mnctional psychiatric illncss in thc carly twcnticth ccntury. Ahcr thc
discovcry of thc biological causcs of mcntal illncsscs, such as gcncral parcsis
[ccntral ncrvous systcm syphilis) and crctinism [mcntal rctardation causcd
by thyroid dchcicncy) , psychiatric illncsscs camc to bc dividcd into two
catcgorics. cryan|cand }nc||cna|. rganic psychiatric illncsscs wcrc "rcal
illncsscs, causcd by gcrms or abnormal hormonc lcvcls or somcthing clsc
that could bc sccn undcr a microscopc or mcasurcd in a blood tcst. In mnc-
tional illncsscs, on thc othcr hand, it was assumcd that thcrc wasn't anything
wrong with thc pcrson's brain mnctioning in a physical scnsc. Paticnts with
manic- dcprcssivc illncss or schizophrcnia wcrc thought to bc having somc
kind of abnormal rcaction to lifc cvcnts.
Thc gucstion thcn bccamc, Why do somc pcoplc havc thcsc vcry abnor-
mal rcactions whilc othcrs with vcry similar backgrounds and cxpcricnccs
do not It was at this point that thc attcmpt to undcrstand and trcat thcsc ill-
ncsscs turncd away hom mcdicinc and toward psychology. Sigmund Ircud
spcnt his lifctimc trcating and trying to undcrstand paticnts who wcrc un-
happy in thcir rclationships, disappointcd in thcmsclvcs fr thc choiccs thcy
had madc, pcrhaps conmscd and anxious about dccisions thcy wcrc fcing.
Ircud and his fllowcrs dcvclopcd a largc and sophisticatcd systcm fr un-
dcrstanding human bchavior bascd on undcrstanding childhood dcvclop-
mcnt. Thcir trcatmcnts in csscncc consistcd of hclping paticnts undcrstand
thcmsclvcs bcttcr, lct go of grudgcs, rcscntmcnts, and fcars rootcd in thcir
past, and lcarn bcttcr, morc maturc stratcgics to copc with lifc's challcngcs.
This approach has comc to bc callcd dynam|cpsychology or psychiatry and
is bascd on thc bclicf that mcntal lifc is bcst undcrstood as a dynamic in-
tcrplay bctwccn cmotions and intcllcct, prcscnt circumstanccs and uncon-
scious mcmorics of past cxpcricnccs, and many othcr psychological fctors .
Although this approach was cxtrcmcly succcssml in hclping pcoplc with
a widc varicty of problcms and symptoms, practitioncrs of dynamic psy-
chothcrapy soon discovcrcd that it didn`t makc much of an impact on thc
symptoms of illncsscs likc schizophrcnia or bipolar disordcr. Psychologi-
cal thcorics arosc to cxplain thcir symptoms, but thcsc paticnts wcrc simply
considcrcd too intrinsically disturbcd or too psychologically stuntcd or thcir
fmilics too dysmnctional fr thcm to bcncht hom thcrapy. This was a dark
timc fr paticnts with mcntal illncsscs and thcir fmilics, who in chcct wcrc
blamcd fr causing thcsc tcrriblc illncsscs in thc hrst placc.
Thcn a rcvolution occurrcd. lithium, chlorpromazinc, and othcr chcc-
tivc mcdications fr "mnctional illncsscs camc along. In thc I;os, pcrsons
with bipolar disordcr and schizophrcnia lch thcrapists bchind and madc
tracks fr a ncw kind of doctor. thc ||c|cy|ca| psychiatrist, a "pharmaco-
thcrapist,' somconc who would trcat thcm likc rcal pcoplc dcaling with a
"rcal illncss. Ior a timc thcrc was a kind of schism in Amcrican psychiatry
bctwccn thosc who bclicvcd that dynamic psychology bcst cxplaincd mcntal
illncsscs and thosc who bclicvcd that biology was thc kcy that would unlock
thc mystcrics of psychiatric disordcrs.
Whcn I was intcrvicwing fr psychiatric training programs in thc mid-
I;os, this biological psychiatry-dynamic psychiatry split was at its most
pronounccd. Many univcrsity mcdical ccntcr dcpartmcnts of psychiatry
proudly idcntihcd thcmsclvcs to mc as cithcr "biological or "psychody-
namic in thcir approach. Lsually cach camp dcnigratcd thc othcr . psycho-
dynamic psychiatry was "touchy-fccly soh scicncc bascd morc on ninc-
tccnth-ccntury litcrary thcory than on mcdicinc, biological psychiatrists
wcrc "pill-pushcrs who didn`t cvcn talk to thcir paticnts and had no apprc-
ciation fr thc human cxpcricncc. 5ut a fcw dcpartmcnts of psychiatry-
[ohns Hopkins's was onc-wcrc tcaching thcir rcsidcnts that mcntal cxpcri-
cnccs wcrc ncithcr a scrics of chcmical rcactions nor simply a collcction of
dynamically intcrrclatcd thoughts and fcclings, but both. Wc lcarncd at
Hopkins that pcoplc with bipolar disordcr arc still pcoplc, still subj cct to
disappointmcnts and loss, to rclationship problcms and blows to thcir sclf-
cstccm. To rcgard thcir moods as just thc cxprcssion of so many chcmicals
to bc hnc- tuncd with morc chcmicals was to do thcm a grcat disscrvicc.
[Maybc that's how I camc to dislikc that phrasc "chcmical imbalancc') Ior-
tunatcly, this schism has now hcalcd fr thc most part, and cvcn thc most
ardcnt biological psychiatrists rcalizc that psychodynamic undcrstanding of
thc paticnt is a|ways important. Pcrhaps thc most important dcvclopmcnt
has bccn thc conclusion, now supportcd by dccadcs of rcscarch, that thc
most chcctivc trcatmcnt fr pcrsons with mood disordcrs [and, indccd, most
othcr psychiatric illncss) combincs |c|b approachcs, which arc now undcr-
stood to bc complcmcntary rathcr than compcting thcrapcutic approachcs.
Thc varicty of availablc psychological trcatmcnts has broadcncd trc-
mcndously in thc past twcnty-hvc ycars or so. Sophisticatcd tcchnigucs havc
bccn dcvclopcd that work fr particular kinds of problcms. Somc involvc
individual scssions with a thcrapist, othcrs a group sctting. Somc arc fcuscd
on a particular problcm, such as marital or fmily dimcultics or addiction,
othcrs on a particular symptom, such as dcprcssion or panic attacks. Somc
arc dcsigncd to last only a fcw scssions, othcrs arc morc opcn- cndcd. Somc
arc not "thcrapy in thc traditional scnsc at all. support groups, madc up of
individuals who ohcr guidancc and support to cach othcr, don`t cvcn includc
1 M VAi
a "thcrapist' Morcovcr, a lot of rcscarch has bccn donc to dctcrminc which
psychological trcatmcnts work bcst fr which problcms. Thc prcscription of
a particular kind of counscling or thcrapy fr a particular kind of problcm
is ohcn backcd up by as much rcscarch as is thc prcscription of a particular
What Can Thcrapy o?
o onc today would cvcn think of rccommcnding counscling or thcr-
apy as thc only trcatmcnt fr bipolar disordcr, to do so would constitutc
malpracticc. 5ut bccausc wc havc highly chcctivc mcdications fr this ill-
ncss, somc doctors, and pcrhaps many morc paticnts, want to turn away
hom counscling and thcrapy altogcthcr and approach thc illncss as a purcly
"chcmical problcm that has a purcly "chcmical solution. This is a mistakc,
fr scvcral rcasons.
Iirst of all, thc diagnosis of bipolar disordcr is almost always a traumatic
cvcnt, not only fr paticnts but fr thcir fmily mcmbcrs as wcll. In addition
to thc cmotional turmoil that is thc symptom of thc illncss itsclf, thcrc is
an cmotional rccling that rcsults hom coming fcc to fcc with fcars about
how this diagnosis will ahcct onc's lifc. Vagucly fmiliar tcrms likc man|c-
dcrcss|cnand all- too- fmiliar tcrms likc mcn|a| |||ncss conjurc up all sorts
of conmscd and conmsing idcas and fcclings. "Why has this happcncd to
mc [or pcrhaps "This can`|bc happcning to mc| ) and "My lifc will ncvcr
bc thc samc and "Whosc fult is this arc only somc of thc thoughts and
gucstions that start spinning through thc minds of pcoplc ahcctcd by this
diagnosis. Rcmcmbcr that I dcscribcd thcrapy as "providing good infrma-
tion, objcctivc fccdback, and solid cncouragcmcnt in a supportivc, conhdcn-
tial sctting' It bccomcs obvious, docsn`t it, that this kind of psychological
trcatmcnt is going to bc ncccssary and vcry hclpml Somc rcscarch suggcsts
that thc hrst ycar ahcr a diagnosis of bipolar disordcr is a crucial timc fr
pcrsons with thc disordcr and that thc cducation, support, and cncouragc-
mcnt that psychothcrapy providcs arc vcry important in making trcatmcnt
succcssml in thc long tcrm. '
Anothcr traumatic cvcnt that pcrsons with bipolar disordcr fcc all too
hcgucntly is rclapsc. Thc managcmcnt of bipolar disordcr is still fr hom
pcrfcct, and dcspitc cvcryonc's bcst chorts, rclapsc can and docs occur. Many
paticnts fccl that thcy'rc "back to sguarc onc, thcy blamc thcmsclvcs or thcir
mcdication or thcir doctor, thcy bccomc angry, disappointcd, discouragcd,
and conmscd about what to do ncxt. Again, counscling hclps thc pcrson
put things back into pcrspcctivc, gct ovcr thc sctback, and movc on. I shall
discuss individual thcrapy in morc dctail latcr in this chaptcr.
Group Psychothcrapy
Psychothcrapy can bc vcry chcctivc in a group sctting. Thc worry I ohcn
hcar cxprcsscd by paticnts fr whom group thcrapy is rccommcndcd is that
thcy don`t want to "sit around listcning to othcr pcoplc's problcms wcck
ahcr wcck. 5ut no group thcrapist worth his salt is going to lct thc group dc-
tcrioratc into a "pity party, instcad, hc will guidc thc group mcmbcrs onto
thc track of lcarning hom, and hclping solvc, onc anothcr's problcms-not
just vcntilating about thcm. An cxccllcnt way to bccomc a bcttcr problcm
solvcr is to scc how othcr pcoplc arc solving, or filing to solvc, thcir own
problcms. 5y obscrving and bcing askcd to obj cctivcly rcact to anothcr pcr-
son`s problcms, group mcmbcrs lcarn how to think morc obj cctivcly, and
lcss cmotionally, about thcir own.
In traditional group psychothcrapy, thc groups arc usually madc up of
pcrsons with a varicty of problcms. In thc trcatmcnt of bipolar disordcr,
howcvcr, bcmcycnccus groups [composcd cxclusivcly of pcrsons with bi-
polar disordcr) havc bccn studicd morc and havc bccn shown to bc chcctivc.
Scvcral studics show that bipolar- disordcr paticnts in group thcrapy havc
fcwcr rclapscs and improvcd productivity at work or school. ' Thc rcscarch
suggcsts that thc sharcd aspcct of thc problcms sccms to bc vcry import-
ant to thc thcrapcutic cxpcricncc. Pcrsons with bipolar disordcr who arc in
groups with othcr bipolar- disordcr paticnts rcport that thc practical advicc
thcy rcccivc about living with thc disordcr is vcry hclpml. Thcir undcrstand-
ing of thc disordcr, of how it ahccts thcir rclationships and sclf- attitudcs, is
cnhanccd, and thc guidancc thcy rcccivc hom group mcmbcrs is pcrccivcd
as vcry valuablc. ' This aspcct of group thcrapy-sharing and lcarning hom
onc anothcr-is thc basis of anothcr typc of "thcrapy,' onc that docsn`t rc-
guirc a thcrapist. pccr support groups. Wc shall discuss this hclping frmat
in chaptcr 2O.
Anothcr psychothcrapcutic group approach dcvclopcd fr pcrsons with
bipolar disordcr is thc sycbc- cduca||cna|yrcu,which can bc thought of as
combining morc traditional group thcrapy with a didactic, instructional ap-
proach. This kind of group ohcn includcs rcading matcrials and discussion
gucstions about bipolar disordcr and infrmation about symptoms, about
thc warning signs of rclapsc, and about how to bcttcr communicatc with
fmily mcmbcrs, cmploycrs, and co-workcrs rcgarding thc illncss, among
othcr topics . A prcscntation of fcts about thc illncss or tcchnigucs fr dcal-
ing with it bccomcs a taking- oh point fr a discussion of thc individual's
cxpcricnccs and using ncw knowlcdgc to fccl bcttcr and mnction morc cf-
fcctivcly. A study of paticnts who wcrc "minimally symptomatic comparcd
how chcctivc attcnding a psycho- cducational group was, comparcd to rc-
cciving individual cognitivc bchavioral thcrapy. Thc rcscarchcrs fund that
1 M VAi
cach trcatmcnt improvcd thc paticnts' mnctional lcvcl and rcsidual symp-
toms-and thc group trcatmcnt was much lcss cxpcnsivc. Ior this and othcr
rcasons, this approach is gaining fvor. Or. Oavid Miklowitz, who has spcnt
morc than a dccadc invcstigating thc chcctivcncss of psycho-cducational
trcatmcnt, has cvcn dcvclopcd a program callcd "Iacilitatcd Intcgratcd
Mood Managcmcnt that can bc complctcd in only hvc scssions. ' umcr-
ous studics havc shown psycho- cducation to bc a valuablc adjunct to othcr
trcatmcnt approachcs to bipolar disordcr.
Indvdua Thcrapy mr cprcsson
As wc saw in carlicr chaptcrs, availablc pharmaccutical trcatmcnts fr
thc dcprcsscd phasc of bipolar disordcr arc lcss than pcrfcct by a long shot.
Thc mood stabilizcrs arc not complctcly chcctivc as antidcprcssants fr
somc paticnts, and antidcprcssant mcdications carry thc risk of prccipitat-
ing mania or accclcrating thc hcgucncy of cyclcs. 5ut psychothcrapy has
a provcn track rccord in hclping with dcprcssion and, as fr as wc can tcll,
has no risk of prccipitating mania or of accclcrating thc coursc of bipolar
"ow wait a minutc,' I can hcar you say, "I'vc bccn rcading through
this cntirc book that thc moods of bipolar disordcr arc causcd by abnormal
brain chcmistry, and now you want mc to bclicvc that psychothcrapy can
trcat thc dcprcssivc phasc of bipolar disordcr Wcll, pcrhaps "psychothcr-
apy can trcat thc dcprcssivc phasc of bipolar disordcr ovcrstatcs thc casc
a bit, but thcrc is somc rcscarch showing-by implication, at lcast-that it
may bc vcry hclpml.
In thc I6os Or. Aaron 5cck and his collcagucs dcvclopcd a thcory of
dcprcssion and psychothcrapcutic trcatmcnt fr it callcd ccyn|||vc- |cbav-
|cra| |bcray, or C5T fr short.` This typc of psychothcrapy has bccn rc-
scarchcd morc thoroughly than most othcrs and has a provcn track rccord
in hclping with symptoms of dcprcssion, in somc studics-though not in
othcrs-it has bccn fund to work as wcll as antidcprcssant mcdication fr
somc paticnts, or cvcn bcttcr."
Thc thcory of cognitivc thcrapy maintains that pcoplc who arc chron-
ically or hcgucntly dcprcsscd havc dcvclopcd a distortcd vicw of thcmsclvcs
and of thc world and havc adoptcd ccrtain pattcrns of thinking and rcacting
to challcngcs that pcrpctuatc thcir problcms. This cmphasis on thinking, or
ccy|||cn,lcnds thc thcory and thc thcrapy its namc. As wc saw in chaptcr
i, dcprcsscd pcrsons tcnd [I) to think ncgativcly about thcmsclvcs, z) to
intcrprct thcir cxpcricnccs in a ncgativc way, and [ ) to havc a pcssimistic
vicw of thc mturc. Cognitivc thcory calls this thc "cognitivc triad' Thc thc-
ory mrthcr proposcs that all this ncgativc thinking causcs a pcrson to dc-
vclop a rcpcrtoirc of mcntal habits callcd "schcmas or "ncgativc automatic
thoughts that spring into action and rcinfrcc thc ncgativc thinking .

[ohn is a thirty-two-ycar- old computcr spccialist whosc idca fr a ncw
projcct has just bccn turncd down by his company. Hc comcs to his
thcrapy scssion and brings along a lcngthy handwrittcn critiguc of thc
projcct that thc scnior vicc-prcsidcnt of his division lch bchind ahcr
coming by [ohn`s cubiclc to tcll him that thc projcct had bccn turncd
"You scc, I should havc known bcttcr than to takc on that big
a proj cct. Thc scnior vicc- prcsidcnt, no lcss, comcs by with thc bad
ncws. ` 5cttcr luck ncxt timc, shc said. ow I'm ncvcr going to movc up
in this company'
"Why do you say that I askcd.
"If somconc that high up thinks I'm incompctcnt, I'm donc fr.
That's thc last timc I bothcr trying somcthing I'm not cut out fr'
"Oid shc say shc thought you wcrc incompctcnt
"Wcll, no, of coursc not'
"I scc. This vicc-prcsidcnt docsn`t tcll pcoplc what shc thinks'
"h, no, that's not truc at all. Shc's got a rcputation fr coming
right out with hcr opinions about things'
"5ut shc trcats you dihcrcntly hom cvcryonc clsc
[ohn bcgan to gct a littlc annoycd. "Wcll, I wouldn`t think so, but
how should I know I'd ncvcr talkcd with hcr bcfrc'
"What do you makc of that I askcd. "Thc fct that shc camc in
pcrson to givc you thc ncws about your proposal
"Wcll, I did think it was unusual'
"Could it mcan shc was imprcsscd with somc aspccts of your pro-
posal and wantcd to mcct you
"Wcll, I supposc that's possiblc'
I continucd rcintcrprcting [ohn's ncgativc assumptions. "And how
about thc handwrittcn critiguc
"It was rcally ncgativc,' [ohn wcnt on glumly. "Shc wcnt through
cvcry point and shot thcm down onc by onc'
"Whcn had you scnt thc proposal to Ms. Kaiscr How long did shc
havc to look at it
"h, I didn`t scnd it to Kaiscr, shc's ovcr thc wholc division. I had
scnt it to 5ob Rodncy, my tcam lcadcr. I gucss hc scnt it up to hcr, but I
don`t know how long shc spcnt with it'
"Wcll, shc must havc spcnt scvcral hours with it if shc gavc you
back such a carcmlly organizcd critiguc. Oon't you think
1q0 M VAi
"Ycah, I gucss shc wouldn`t havc takcn all that timc and troublc if
shc had thought it was worthlcss'
"And your tcam lcadcr must havc thought it had somc potcntial
if hc scnt thc proposal to b|sboss. Havc you askcd him fr somc fccd-
"o, I assumcd hc'd bc down on mc fr it, too'
"5ut do you scc how your ncgativc assumption stoppcd you hom
chccking in with your tcam lcadcr and prcvcntcd you hom gctting
what could havc bccn positivc fccdback and cncouragcmcnt hom
"I scc what you mcan. If I hadn`t jumpcd to conclusions, I might
havc gottcn somc positivc strokcs'

[ohn is down on his talcnts and assumcs cvcrybody clsc is, too. In situ-
ations that can bc intcrprctcd many dihcrcnt ways, both positivc and ncga-
tivc, hc tcnds to go fr thc ncgativc rathcr than to scck altcrnativc positivc
cxplanations . This in turn somctimcs causcs him to do things that rcinfrcc
his ncgativc thinking, and thc vicious cyclc rcpcats itsclf. This might sccm
to bc a trivial cxamplc, but it's not dimcult to comc up with scvcral ncgativc
schcmas that pcoplc with bipolar disordcr arc pronc to.
Ncya||vc: "I got manic cvcn though I was taking my lithium. It docsn't
mattcr what I do. What's thc usc
Rca| |s||c: "Rclapscs occur cvcn with mcdication. It might havc bccn
much worsc and lastcd much longcr if I hadn't bccn on mcdication. Pcrhaps
this ncw mcdication will bc morc chcctivc fr mc'
Ncya||vc: "Lvcryonc will bc avoiding mc whcn I go back to work. o
onc wants to work with a mcntally ill pcrson'
Rca| |s||c:"Somc pcoplc might avoid mc at work, pcrhaps many at hrst.
5ut whcn thcy scc that I'm thc samc old mc, thcy'll comc around. And thosc
who don't arc pcoplc I don`t want as hicnds anyway'
Cognitivc-thcrapy tcchnigucs morc spccihcally fcuscd on bipolar dis-
ordcr havc also bccn dcvclopcd. Part of thc trcatmcnt dcals with thc ncgativc
automatic thoughts that intcrfcrc with trcatmcnt by mcdication. Ior cxam-
plc, if a pcrson with bipolar disordcr is troublcd by thc ncgativc automatic
thought "Taking mood- stabilizing mcdication is a sign of pcrsonal wcak-
ncss cvcry timc shc takcs a dosc of lithium, shc might bc morc likcly to skip
doscs or stop taking thc mcdication altogcthcr. Cognitivc thcrapy works on
thc psychological barricrs to propcr trcatmcnt by rcplacing automatic ncga-
tivc thoughts with rcalistic oncs. '
Cognitivc thcrapy has bccn provcn to bc chcctivc in thc trcatmcnt of
dcprcssion. Clcarly it cannot rcplacc mcdication trcatmcnt fr bipolar dis-
ordcr, but pcrhaps morc than any othcr frm of psychothcrapy, it holds grcat
promisc fr bipolar paticnts.
Mcw Psychothcrapcs mr BpoIar sordcr
Ior many ycars psychiatrists and thc thcrapists who work with thcm
in trcating paticnts with bipolar disordcr havc had a sort of intuition that
thcrc arc fcwcr rclapscs among paticnts who undcrstand thcir illncss and
thcir trcatmcnt bcttcr, who work on lcarning to copc bcttcr with thc strcsscs
and dimcultics that cvcrybody fccs, and whosc fmily mcmbcrs arc also
infrmcd and supportivc. Psychiatrists havc also obscrvcd that lifc strcsscs,
dimcult rclationships at homc, and cvcn disruptions of slccp cyclcs sccm to
bring on symptoms and ahcct thc coursc of thc illncss. hcn, though, thcy
hnd it hard to pcrsuadc paticnts-and somctimcs hard to pcrsuadc thcm-
sclvcs, pcrhaps-that a coursc of traditional psychothcrapy is what's nccdcd.
Psychiatrists havc donc thcir bcst to spcnd timc with paticnts and thcir
fmilics, answcring thcir gucstions about bipolar disordcr and its trcatmcnts,
trying to pcrsuadc paticnts with marital problcms to gct marital thcrapy and
paticnts with j ob problcms to gct carccr counscling, and cncouraging thcm
to lcarn about strcss managcmcnt, watch thcir slccp habits, and stccr clcar
of conflict and dimcult situations whcncvcr possiblc. 5ut such intcrvcntions
arc timc- consuming or cxpcnsivc [or both), thcy arc dimcult to put into
practicc ["Stccr clcar of conflict How do I do |ba|, Ooc) , and until rc-
ccntly wc havc had only thc imprcssion that thcsc arc important intcrvcn-
tions, with littlc hard data to back up our rccommcndations .
5ut now scvcral rcscarch tcams arc dcvcloping trcatmcnt modcls of psy-
chological thcrapy fr bipolar paticnts that draw on thcsc sorts of imprcs-
sions. Thc trcatmcnt modcls takc into account thc availablc rcscarch about
thc particular kinds of strcsscs that causc symptoms in bipolar paticnts,
and thcy incorporatc thc cxpcricnccs of clinicians who havc trcatcd many,
many bipolar paticnts . Thosc trcatmcnts cmphasizc issucs such as paticnt
and fmily cducation about thc illncss, strcss managcmcnt and conflict rcs-
olution, and closc attcntion to thc strains in fmily and marital rclationships
that arc ohcn causcd by this illncss in cvcn thc hcalthicst fmily units. Thcsc
rcscarch tcams arc tcsting thcir idcas with wcll- dcsigncd clinical studics, and
thc rcsults havc bccn vcry cncouraging. nc or anothcr or a combination of
thc thcrapics thcy arc tcsting may wcll bccomc standard rccommcndations
fr paticnts with bipolar disordcr in thc mturc.
Thc trcatmcnts in gucstion dihcr hom standard psychothcrapy in scv-
cral ways. Traditional psychothcrapy is ohcn unfcuscd and "cxploratory,
thc paticnt and thc thcrapist work on thc issucs that thc paticnt idcntihcs [fr
cxamplc, "I want to lcarn to makc bcttcr choiccs in my rclationships), and
1q2 M VAi
trcatmcnt is opcn- cndcd. thc paticnt is in thcrapy as long as hc hnds it bcn-
chcial and has an issuc to work on. Thcsc ncw trcatmcnts, howcvcr, arc vcry
fcuscd. Thc fcus varics slightly in thc two currcnt modcls. onc fcuscs on
fmily cducation and communication and thc othcr on lifcstylc rcgulariza-
tion and strcss managcmcnt. In both kinds of trcatmcnt, thc thcrapist ohcn
acts morc likc a tcachcr or coach than a counsclor, and thc goals arc to dc-
vclop concrctc solutions to rcal problcms and to lcarn about and mastcr ncw
problcm-solving tcchnigucs. Sincc thc paticnt ohcn docsn`t bring "issucs to
thc thcrapy, thcrc is a spccihcd timc coursc to thc trcatmcnt, thc main work
of thc trcatmcnt is hnishcd within a ccrtain timc pcriod, although thcrc is a
maintcnancc phasc that can bc indchnitc.
Bcbav|cra|}am| |y manaycmcn|}cr ||c|ard|scrdcrcmphasizcs thc pa-
ticnt's fmily unit. To somc cxtcnt this modcl has grown out of rcscarch
showing that paticnts with schizophrcnia had morc illncss rclapscs if thcrc
wcrc conflicts and strcsscs at homc and within thc fmily. This thcrapy works
hard at fmily support. Lducating thc paticnt and hcr fmily mcmbcrs about
thc symptoms of bipolar disordcr and its trcatmcnts is a priority, cmpha-
sizing that bipolar disordcr is indccd an illncss and that its symptoms arc
not undcr voluntary control. Iamily scssions arc hcld to idcntify dimcul-
tics and conflicts within thc fmily unit-whcthcr causcd by thc illncss or
by othcr, pcrhaps prccxisting, fctors or situations. Conflict rcsolution and
problcm-solving tcchnigucs arc prcscntcd and practiccd, and hcalthy com-
munication skills arc dcvclopcd through rolc playing and rchcarsals.
In|crcrscna|andscc|a|rby|bm |bcray [IP/SRT) puts morc cmphasis
on paticnts as individuals and on thcir "social rhythm' 5ascd on thc ob-
scrvation that slccp dcprivation and othcr disruptions of body rhythms can
bring on symptoms, this trcatmcnt cmphasizcs stability and strcss managc-
mcnt. It involvcs having paticnts track thcir mood statcs on a daily basis and
also thcir daily routinc with a sort of chccklist of activitics callcd thc scc|a|
rby|bm mc|r|c.
In thcir scssions thc paticnt and thc thcrapist rcvicw thcsc diarics and
also thc paticnt's "intcrpcrsonal invcntory [a list of thc pcrsons in thc pa-
ticnt's social nctwork) with an cyc toward idcntifying conflicts and strcsscs
in rclationships. Thc thcrapist and thc paticnt work on idcntifying cmotional
or physical strcsscs and fctors in thc cnvironmcnt that upsct daily rhythms
and cmotional stability. Thc goal is to "hnd a hcalthy balancc bctwccn daily
rhythm stability, social activity, social stimulation and mood statcs' '" Al-
though it's still too soon to know thc impact of IP/SRT on thc coursc of
bipolar disordcr ovcr timc, carly rcsults of thc rcscarch indicatc that IP/SRT
paticnts madc morc hcalthy lifcstylc changcs and showcd grcatcr stability in
daily routincs and rhythms than a control group of paticnts did. ' '
"TradtonaI" IndvduaI Psychothcrapy
I hopc I havcn`t givcn you thc imprcssion that traditional psychothcrapy
isn`t uscml fr paticnts with bipolar disordcr. Quitc thc contrary. Kay Rcd-
hcld [amison has writtcn. "At this point in my cxistcncc, I cannot imaginc
lcading a normal lifc without both taking lithium and having had thc bcn-
chts of psychothcrapy. Lithium prcvcnts my scductivc but disastrous highs,
diminishcs my dcprcssions . . . and makcs psychothcrapy possiblc. 5ut, in-
chably, psychothcrapy bca|s. It makcs somc scnsc of thc conmsion, rcins
in thc tcrriing thoughts and fcclings, rcturns somc control and hopc and
possibility of lcarning hom it all' ' '
So fr i n this chaptcr wc'vc talkcd about "situational supportivc coun-
scling fcuscd on cpisodcs of illncss, cithcr thc hrst onc or a rclapsc. Thc
goal of this counscling is to hclp paticnts dcal with thc acutc strcsscs of di-
agnosis, hospitalization, rcintcgration back into thcir job, or othcr spccihc
issucs rclatcd to an cpisodc of illncss. Wc'vc discusscd thc cognitivc thcrapy
of dcprcssion, a coursc of trcatmcnt that might bc rccommcndcd fr chronic
or smoldcring dcprcssivc symptoms that mcdication alonc docsn't sccm to
guitc takc carc of. In thc prcccding scction wc discusscd somc ncw thcrapics
that aim to tcach paticnts and thcir fmilics how to smooth out thc bumpy
spots in thcir rclationships, improvc communication and conflict-rcsolu-
tion skills, and rcgularizc thcir social rhythms. Thcsc trcatmcnts arc pcrhaps
morc prcvcntivc than thc othcrs and might bc thought of as providing psy-
chological immunization against mturc problcms as wcll as ways of dcaling
with prcscnt oncs.
What, thcn, of traditional psychothcrapy 5y |rad|||cna|sycbc|bcray
I mcan individual mcctings with a thcrapist, usually ovcr an cxtcndcd pc-
riod of timc [months or ycars) , in which thc pcrson in trcatmcnt discusscs
his past and prcscnt cxpcricnccs and fcclings with thc goal of sclf- undcr-
standing, sclf- acccptancc, and pcrsonal growh. Dynam|cor |ns|yb|-cr|cn|cd
sycbc|bcray is thc samc thing. ) Oisappointmcnts and accomplishmcnts,
ahcctions and cnmitics, fcars, inspirations, passions, and worrics-all arc
"grist fr thc mill of thcrapy, as psychothcrapists arc fnd of saying. Thc pa-
ticnt and thc thcrapist will, of coursc, talk about symptoms likc sadncss and
anxicty too, but traditional thcrapy sccs symptoms as indicators of undcr-
lying psychological conflicts rathcr than as thc fcus of trcatmcnt in and of
thcmsclvcs. Traditional psychothcrapy cmphasizcs cxploration of thc mcan-
|nyof symptoms, thc dcvclopmcnt of sclf-awarcncss and maturity.
So whcn would wc rccommcnd traditional psychothcrapy to a pcrson
with bipolar disordcr Ior what typcs of problcms would it bc hclpml 5a-
sically, fr thc samc typcs of problcms that pcoplc without bipolar disordcr
go to thcrapists fr. dcaling with psychological traumas and sctbacks-past
1qq M VAi
and prcscnt-that, undcrstandably, causc fcclings of sadncss, angcr, or anx-
icty, or thought pattcrns, sclf- attitudcs, and intcrpcrsonal stylcs that disrupt
a pcrson's ability to bc happy in rclationships, chcctivc at work, carchcc in
play, and conhdcnt in making dccisions about thc mturc. Sounds likc a tall
ordcr, docsn`t it Wcll, of coursc it is. That is why psychothcrapists ohcn
study and train in thcir profcssion fr as many ycars as physicians train in
thcirs. That is why pcoplc arc somctimcs in thcrapy fr months or cvcn fr
ycars at a timc. That is why psychothcrapy is such an intcnsc, powcrml cx-
pcricncc and thc thcrapcutic rclationship bctwccn paticnt and thcrapist a
uniguc onc.
5ipolar paticnts ohcn havc had morc than thcir sharc of sctbacks and
psychological traumas-both past and prcscnt. Pcrsons with bipolar disor-
dcr, bccausc it is a gcnctic illncss, ohcn havc had dimcult, cvcn traumatic
childhoods. Pcrhaps a parcnt was amictcd with thc illncss, pcrhaps thc par-
cnt could not or would not rcccivc propcr trcatmcnt, and thc child may havc
suhcrcd disruptions to fmily lifc, pcriods of povcrty or homclcssncss, or
cvcn physical or cmotional abusc. Psychothcrapy can bc cnormously bcnc-
hcial in hclping pcoplc fcc and work through thcir dimcult pasts, lct go of
thc angcr, rcscntmcnt, and fcar that ohcn comcs out of thcsc cxpcricnccs,
and movc on with thcir livcs.
Thc fct that a pcrson has bipolar disordcr can makc ordinary lifc dcci-
sions sccm complcx and important lifc dccisions sccm ovcrwhclming. Thcrc
is no bcttcr way of dcaling with thcsc sorts of anxictics and apprchcnsions
than traditional psychothcrapy. I rcmcmbcr a young woman who camc to
scc mc fr a routinc mcdication-monitoring appointmcnt whcn I was work-
ing in thc vcry busy mcdication clinic of a community mcntal-hcalth ccntcr,
a clinical sctting in which paticnts wcrc schcdulcd cvcry twcnty minutcs.
"I'vc bccn dating a man fr scvcral months now, and I think hc might ask mc
to marry him,' shc told mc. Shc lookcd worricd. "I havcn't told him about
my illncss. I don`t know what to tcll him. How do you think I should handlc
this I starcd at hcr hclplcssly fr a momcnt and panickcd just a littlc whcn
I hcard thc nursc slipping thc chart of thc ncxt paticnt into thc bin outsidc
thc intcrvicwing-room door. I hopc I didn't sound as rushcd as I fclt whcn
I tricd to convincc hcr that thc situation raiscd an cnormous numbcr of
complcx issucs. Adcguatcly dcaling with thc gucstions of how, whcn, whcrc,
why, and with whom shc discusscd hcr diagnosis was going to nccd much
morc than onc-or a dozcn-twcnty- minutc appointmcnts with mc.
I doubt vcry much that this was thc hrst timc this young woman had
bccn conmscd about what to tcll somconc about hcr diagnosis. Pcrhaps shc
had muddlcd through othcr situations at work, at church, or in hcr ncigh-
borhood, maybc saying nothing about hcr diagnosis bccausc of fcclings of
shamc, or maybc blurting out too much about hcrsclf and thcn fccling vul-
ncrablc and cxposcd. Pcrhaps bcing diagnoscd with bipolar disordcr rcac-
tivatcd fcclings shc had strugglcd with in childhood or adolcsccncc about
bcing tcascd fr bcing too ft or too skinny-or pcrhaps, morc likcly in a bi-
polar paticnt, fr bcing "hypcr or "wcird' I was surc that sincc wc had dis-
cusscd thc fct that bipolar disordcr is a gcnctic illncss, a possiblc marriagc
proposal raiscd gucstions in hcr mind about having childrcn who might bc
ahcctcd by thc disordcr. How had thc diagnosis ahcctcd hcr idcntity as a
potcntial parcnt, as a woman r pcrhaps nonc of thcsc issucs nccdcd to bc
cxplorcd but instcad othcr, complctcly dihcrcnt oncs. Wcll, all thcsc issucs
arc what good old- fshioncd oncc- a-wcck "How do you fccl about that
psychothcrapy is all about.
Psychothcrapy n BpoIar sordcr.
Is It RcaIIy Mcccssary?
All thc psychiatrists I know talk about how much timc thcy spcnd try-
ing to pcrsuadc thcir bipolar paticnts to supplcmcnt thcir mcdication trcat-
mcnt with somc frm of thcrapy. Thcrc arc many rcasons why pcrsons with
bipolar disordcr arc rcluctant to do so. Somc paticnts havc madc uncasy
pcacc with taking mcdication fr a psychiatric illncss [or, as thcy might say
to thcmsclvcs, fr a "chcmical imbalancc), but thcy scc going to psycho-
thcrapy as conhrmation of thc "mcntal aspcct of thcir "mcntal illncss' 5ut
if you think about it, thc trcatmcnt of cvcn thc most "mcdical of mcdical ill-
ncsscs-hcart discasc, say, or a rupturcd lumbar disk-usually rcguircs non-
mcdical intcrvcntions, and somctimcs thcsc turn out to bc just as important
as thc pharmaccutical or cvcn surgical intcrvcntions prcscribcd by thc doc-
tor. Thc paticnt with diabctcs would hardly rcgard staying on a hcalthy dict
and watching hcr wcight as unncccssary adjuncts to thc insulin inj cctions
shc rcccivcs. Thc rccovcring coronary-bypass surgcry paticnt wouldn`t ig-
norc thc physician`s rccommcndation fr a cardiac- hardcning cxcrcisc pro-
gram. Would anyonc havc an opcration fr lumbar disk problcms and skip
thc physical thcrapy scssions ahcrward I don't think so.
Wc know that chronic psychological strcsscs makc a wholc varicty of
physical illncsscs morc dimcult to trcat. asthma, high blood prcssurc, irrita-
blc bowcl syndromc. Psychological strcsscs will makc mood- disordcr symp-
toms morc dimcult to control as wcll.
Thc rcscarch rcsults on thc psychothcrapcutic trcatmcnts of bipolar dis-
ordcr arcn`t all in, so wc can`t yct spcci particular thcrapics fr a particular
duration of timc fr particular mood syndromcs. 5ut thc availablc rcscarch
and many ycars of clinical cxpcricncc indicatc that psychothcrapy and coun-
scling havc bccn cnormously hclpml to countlcss paticnts with bipolar dis-
ordcr. If a particular typc of thcrapy or counscling is availablc, is ahordablc,
1q M VAi
and has bccn rccommcndcd by thc physician or trcatmcnt tcam, pcrsons
with bipolar disordcr owc it to thcmsclvcs to takc advantagc of thc uniguc
hcaling powcrs of thcsc marvclous thcrapcutic tcchnigucs.
Thc Psychatrst-Psychomcrapst. An Extnct Spcccs?
You havc probably noticcd that I havc bccn rcfcrring to thc psychiatrist
and thc psychothcrapist as two dihcrcnt individuals. Lnfrtunatcly, most pa-
ticnts in Amcrica do not hnd onc pcrson scrving both mnctions. It would, of
coursc, bc prcfcrablc fr all sorts of rcasons fr thc pcrson prcscribing mcd-
ication and thc pcrson doing psychothcrapy to bc onc and thc samc individ-
ual. 5ut fr a varicty of complicatcd rcasons, most pcoplc with bipolar dis-
ordcr will scc a psychiatrist fr mcdication managcmcnt and a nonphysician
thcrapist-ohcn a social workcr or psychologist-fr thcrapy. Somc of thc
rcasons fr this statc of ahairs arc thc changcs in mcdication managcmcnt of
bipolar disordcr that havc comc about with thc dcvclopmcnt of ncw mcdi-
cations, thcrc arc now so many dihcrcnt pharmaccuticals uscd in psychiatry
that staying skillcd in thcir usc has bccomc morc and morc timc- consum-
ing. Pcrhaps cvcn morc signihcantly, as morc and morc chcctivc mcdications
bccomc availablc fr morc psychiatric problcms, morc and morc paticnts
want [ and nccd) to scc a psychiatrist fr thcir trcatmcnt. Thcrc simply arcn't
cnough psychiatrists to do both mcdication managcmcnt and thcrapy, cspc-
cially in busy clinics. Sincc mcdical school and psychiatric training takc lon-
gcr and cost morc than thc training rcguircd to bccomc a psychothcrapist,
psychiatrists arc usually morc cxpcnsivc than othcr profcssionals. Whcn thc
administrator of a busy clinic or Hcalth Maintcnancc rganization [HM)
is looking to stah thc organization`s mcntal-hcalth program, "split trcat-
mcnt-psychiatric trcatmcnt split bctwccn a psychiatrist fr mcdication
managcmcnt and a nonphysician thcrapist fr psychothcrapy or counscl-
ing-mcans morc cost-chcctivc trcatmcnt fr paticnts.
Thc supcrior cost- chcctivcncss of "split trcatmcnt allows so many morc
paticnts to rcccivc psychiatric trcatmcnt so much morc chcaply that it's dim-
cult to cnvision a rcturn to thc days whcn psychiatrists did thcrapy and prc-
scribcd mcdications, too. Iortunatcly, thcrc arc cxccllcnt training programs
fr clinical social workcrs, psychologists, and counscling profcssionals that
arc producing supcrb psychothcrapists. And as wc havc sccn in this chap-
tcr, psychothcrapy is bccoming morc spccializcd, too. It has bccomc ncarly
impossiblc to bc an cxpcrt thcrapist and at thc samc timc an cxpcrt psycho-
pharmacologist. Ior all of thcsc rcasons, thc mcdication managcmcnt and
thc thcrapy of thc pcrson with bipolar disordcr will usually bc handlcd by
two profcssionals rathcr than onc.
1D 1O1d1 I1SO1UO1
L M A 1 H 2
approachcs havc bccn stumblcd upon morc or lcss by accidcnt-fr cxam-
plc, thc discovcry of thc thcrapcutic chccts of lithium-and although thcy
havc bccn rchncd by dccadcs of cxpcricncc, thcy arc still largcly what physi-
cians call cm|r|ca|.This mcans that thc trcatmcnt is bascd on accumulatcd
clinical cxpcricncc rathcr than on a truc undcrstanding of thc mcchanism of
thc discasc or symptom in gucstion. '
Thcrapcutc RcsuIts as a Gudc to Trcatmcnt
Although wc havc a trcmcndous amount of cxpcricncc in thc usc of
pharmaccuticals to trcat bipolar disordcr and havc data on thcir chcctivc-
ncss in largc groups of paticnts, thc trcatmcnt of individual paticnts with thc
illncss is ohcn guidcd by trcatmcnt rcsults rathcr than by thc kinds of hard
data physicians usc to trcat othcr illncsscs. What do I mcan by this Lct mc
cxplain by looking at a vcry dihcrcnt kind of illncss, pncumonia.
A young man is rushcd to thc cmcrgcncy room with a high fcvcr, a pain
in his chcst, dimculty brcathing, and a congcstcd cough. Thc doctor ordcrs
a chcst x-ray. A spccimcn of thc young man`s sputum is rushcd oh to thc
laboratory, and a tiny droplct is sprcad on a microscopc slidc, immcrscd in a
spccial dyc callcd a Cram stain, and cxamincd undcr thc microscopc. Morc
tiny droplcts arc sprcad ovcr thc surfcc of scvcral flat dishcs [pctri dishcs)
containing mixturcs of protcins and othcr nutricnts that arc known to causc
various bactcria to grow. n onc of thc dishcs arc a somc littlc papcr disks
that havc bccn soakcd in dihcrcnt antibiotics.
Thc lab rcsults start coming in. Thc young man's chcst x-ray shows that
onc of thc lobcs of his right lung is hllcd with fluid. Thc Cram stain rcvcals
that his phlcgm is loadcd with bactcria aligncd in pairs and linkcd into short
chains. thc pncumococcus. Thc diagnosis is clcar. pncumococcal pncumo-
ni a. Thc doctor starts thc young man on pcnicillin, an antibiotic known to
bc chcctivc against most strains of pncumococcus, and within cight hours
his fcvcr is dropping. Thc dosc of pcnicillin and thc lcngth of timc thc young
man will nccd to takc it havc bccn dctcrmincd by ycars of cxpcricncc, calcu-
latcd to thc milligram and to thc hour.
In a day or so thc lab rcports that thc pctri dish containing thc pncu-
mococcus's fvoritc fod is mll of colonics of bactcria that othcr, morc so-
phisticatcd tcchnigucs now dchnitcly conhrm as pncumococcus. Thc bcst
ncws of all is that in thc dish containing thc littlc disks of antibiotics, thcrc is
a widc, clcar halo around thc pcnicillin disk. thc pcnicillin is inhibiting thc
growth of thc strain of bactcria causing this particular casc of pncumonia.
Thc young man docs not havc a pncumonia causcd by a pcnicillin- rcsistant
bug. Thus, his spccdy rccovcry is assurcd.
Thc doctor trcating this young man had guitc a bit of hard data on
which to basc hcr trcatmcnt dccisions. Thc x-ray indicatcd that this was
probably a typical bactcrial lobar pncumonia rathcr than viral pncumonia,
tubcrculosis, or any of thc various othcr conditions with similar symptoms
but that look dihcrcnt on x- ray imagcs. Also-and vcry important fr prog-
nostic purposcs-thc x- ray showcd that only onc lobc was involvcd. With
thc rcsults of thc Cram stain, thc likcly idcntity of thc bactcrial culprit was
dctcrmincd within minutcs, allowing thc guick choicc of a drug known to
bc chcctivc most of thc timc against this typc of gcrm. Thc idcntity of thc
bactcrial culprit was solidly conhrmcd scvcral days latcr whcn it grcw in
thc culturc dish and could bc mrthcr tcstcd. Most important, thc lab rcsults
showcd cxactly which drugs would work against thc gcrm causing thc prob-
lcm in this particular paticnt.
In contrast, whcn a paticnt with manic symptoms comcs into thc LR,
thcrc arc no tcsts to ordcr-just thc cycs and cars and cxpcricncc of thc
psychiatrist. Iortunatcly, or pcrhaps unfrtunatcly, mll-blown mania ohcn
lcads to an unmistakablc diagnosis, and chcctivc antimanic drugs arc rcad-
ily availablc. 5ut what of thc pcrson who comcs to thc omcc and says, `+m
dcprcsscd,' or complains of "mood swings' Thcrc arc many morc diagnostic
possibilitics. Wc know that antidcprcssant mcdications can somctimcs makc
a paticnt with bipolar symptoms worsc. How is a physician to know whcthcr
or not a pcrson who comcs in with symptoms of dcprcssion will turn out to
havc a bipolar illncss Thcrc arc hints, of coursc, such as fmily history, but
wouldn`t it bc fntastic if wc could ordcr a tcst fr bipolar disordcr bcfrc
considcring an antidcprcssant fr a pcrson who is having symptoms of dc-
prcssion 5ut wc can't.
How about thc trcatmcnt, oncc thc acutc symptoms of mania havc bccn
controllcd Lmil Kracpclin dcscribcd somc paticnts who had rcmission of
thcir bipolar symptoms that lastcd fr dccadcs [it was apparcntly guitc rarc
fr this to happcn, but hc obscrvcd thcm, ncvcrthclcss). Oo wc prcscribc a
mood stabilizcr fr a paticnt who might not gct sick again fr tcn or cvcn
twcnty ycars Wouldn't it bc grcat if wc could stop thc mcdication ahcr a
pcriod of timc and havc thc paticnt comc in cvcry couplc of months fr somc
kind of scan that could pick up changcs in brain mnctioning bcfrc symp-
toms bccamc apparcnt That way thc paticnt would takc mcdication only as
it bccamc ncccssary. Somctimcs paticnts rcspond to onc mood stabilizcr but
not anothcr, or to a combination of two mood stabilizcrs but not to cithcr
onc whcn uscd alonc. How to choosc Wouldn`t it bc fntastic if wc could
takc a blood samplc and look fr somc kind of chcmical rcaction around
littlc papcr disks soakcd with lithium or Prozac in a pctri dish to hclp us
choosc chcctivc mcdications fr a particular paticnt
At thc prcscnt momcnt, wc don't havc any blood tcsts, scans, or othcr
laboratory tcsts to makc thc trcatmcnt approach to bipolar disordcr as in-
frmcd and logical as our approach can bc in many othcr illncsscs [although
this, frtunatcly, may changc in thc not-too- distant mturc-morc on this
latcr) .
5ccausc wc do not yct undcrstand thc causcs of bipolar disordcr, thc
mcdical approach to thc trcatmcnt of thc illncss can bc discusscd only in gcn-
cral tcrms. Paticnts arc startcd on onc of thc mcdications that havc provcd
chcctivc in many othcr paticnts with similar symptoms, and if thcsc paticnts'
symptoms arc not chcctivcly trcatcd, othcr intcrvcntions arc tricd. Wc can't
yct pick hom among similar mcdications knowing bcfrchand which onc
of thcm will work bcst. Thcrc is unfrtunatcly a lot of "trial and crror and
"wait and scc whcn it comcs to prcscribing mcdications fr a spccihc pa-
ticnt. This can bc trcmcndously hustrating fr all involvcd-fr thc paticnt,
of coursc, and fr fmily mcmbcrs, and, ycs, fr thc physician, too.
5ut thc good ncws i s that morc and bcttcr mcdications arc bccoming
availablc all thc timc. Twcnty-hvc ycars ago thcrc was only onc mood-stabi-
lizing mcdication, lithium. Tcn ycars ago thcrc wcrc thrcc. ow wc havc at
lcast hvc and scvcral morc on thc way. Thcrc arc casily twicc as many antidc-
prcssants on thc markct as thcrc wcrc only hhccn ycars ago. Thc ncwcr anti-
psychotic mcdications havc fcwcr sidc chccts and also havc mood-stabilizing
propcrtics that thc oldcr agcnts lackcd. As of this writing, thcrc arc mcdica-
tions bcing dcvclopcd that havc cntircly dihcrcnt mcchanisms of action than
currcntly availablc mcdications. Lvcn morc options arc on thc horizon.
1j0 M VAi
Llcctroconvulsivc thcrapy is onc of thc most chcctivc trcatmcnts fr
mood disordcrs and onc of thc safcst mcdical proccdurcs availablc-and it
is probably undcrutilizcd in bipolar disordcr. Transcranial magnctic stim-
ulation and othcr brain-stimulation trcatmcnts may comc to rcplacc LCT
[and pcrhaps cvcn mcdications) if thcy arc ablc to dclivcr what thcy sccm
to bc promising.
Oon`t frgct counscling and psychothcrapy. Rcscarch has provcd how
vcry important this uniguc trcatmcnt is in controlling thc symptoms of mood
disordcrs. Morc chcctivc thcrapy programs fr bipolar disordcr arc bcing
rchncd by rcscarchcrs with studics that arc as rigorous as thosc uscd to cval-
uatc any pharmaccutical.
And I havcn't cvcn talkcd about light thcrapy and slccp manipulation
yct [thosc arc coming in chaptcr i) . Rcscarchcrs havc discovcrcd that cx-
posurc to bright light and changcs in slccp pattcrns can hclp rcgulatc mood
and pcrhaps hclp mcdications work bcttcr and fstcr.
Somc PrncpIcs ot Trcatmcnt
ow and thcn, onc of thc mcdical j ournals publishcs a "trcatmcnt algo-
rithm fr an illncss or disordcr. An algorithm is a stcp-by-stcp proccdurc
fr solving a spccihcd problcm with mathcmatical prccision. A trcatmcnt
algorithm fr acutc mania might look somcthing likc this.
8| l |0| U0
| 0D |SD0S. | Sy0D0S |0| .

8| 80| CD0VUl S80 #1

| 0D |SD0S. | Sy0D0S |0| .

8| 80| CD0VUl S80 #Z LD0| 0U 80| CD0VUl S80 #1

LD0| 0U l | 0| U0
Wcll, you gct thc idca. I don`t hnd trcatmcnt algorithms hclpml i n trcat-
ing individual paticnts cxccpt in a vcry gcncral way. Thcir "if this happcns,
thcn do that approach ncvcr capturcs thc myriad manifcstations of thc dis-
ordcr and thc incvitablc twists and turns of thc world of rcal trcatmcnt and
rcal paticnts, not to mcntion thc spccihc situations and nccds of thc individ-
ual. 5ctwccn iand zoo,, a major clinical trial that includcd morc than
fur thousand paticnts was carricd out to attcmpt to addrcss thcsc complcx-
itics. Although it did includc an algorithm [scvcral of thcm, in fct), onc of
thc main purposcs of thc study was to invcstigatc how "rcal world paticnts,
VAi PPVLLHS 1i 1PL1V 11SLV1V M 1j1
as opposcd to carcmlly sclcctcd paticnts with uncomplicatcd illncss, would
do whcn givcn trcatmcnt bascd on using "bcst practicc cvidcncc-bascd ap-
proachcs. This was thc STLP-5O [thc Systcmatic Trcatmcnt Lnhanccmcnt
Program fr 5ipolar Oisordcr) that I discusscd in chaptcr ;.

Thc STLP- 5O
gcncratcd morc than sixty scicntihc papcrs on cvcry aspcct of thc trcatmcnt
of bipolar disordcr and also on thc coursc of thc illncss, common complica-
tions, thc prognosis, and cvcn gcnctics. Thc STLP- 5O conhrmcd thc chcc-
tivcncss of many acccptcd approachcs to thc trcatmcnt of bipolar disordcr
but also callcd into gucstion somc cgually acccptcd approachcs [ thc most
important of thcsc bcing thc signihcant doubt that thc STLP-5O cast on
thc chcctivcncss of antidcprcssant mcdications in trcating bipolar paticnts) .
Much of this chaptcr i s bascd on hndings of thc STLP- 5O, I will rcvicw somc
of thc principlcs of trcatmcnt that scrvc paticnts [ and thcir physicians) wcll.
With so many powcrml and chcctivc mcdications availablc in psychi-
atry now, it's casy to bccomc impaticnt whcn symptoms don`t subsidc as
guickly as onc would wish. 5ut in thc trcatmcnt of mood disordcrs, a crucial
principlc to rcmcmbcr is to |a/c|bc|cnyv|cw.
Thc mcdications wc usc to trcat mood disordcrs usually takc at lcast two
to fur wccks to cvcn bcgin hclping, and somctimcs much longcr to havc
thcir mll chcct. nc of my mcntors, to drivc homc just this point, is fnd
of tclling his paticnts, " Thc scccndycar on lithium is always bcttcr than thc
hrst' Whcn trcating an cpisodc of bipolar disordcr, it simply docsn't makc
scnsc to changc mcdications guickly. Lvcn hospitalizcd paticnts arc rarcly
wcll scrvcd by adding too many mcdications too guickly-paticnts simply
wind up taking morc mcdications than thcy nccd and at highcr doscs than
may bc ncccssary.
Whcn a diagnosis of bipolar II or cyclothymic disordcr is bcing consid-
crcd, thc timc linc should strctch out cvcn morc. Thc mood changcs in thcsc
variations of bipolar disordcr can somctimcs bc much morc subtlc than
thosc of bipolar I. It may takc thrcc to six months of taking a mood stabilizcr
fr its bcnchcial chccts on a subtly unstablc mood to bccomc apparcnt.

I saw Craig about two wccks ahcr hc had bccn dischargcd hom a hos-
pital in anothcr city. Hc had bccn on a busincss trip and startcd to havc
firly scvcrc manic symptoms. insomnia, racing thoughts, angry irri-
tability. Hc had bccn having good control of his symptoms on a mood
stabilizcr, but a scrics of high-strcss job intcrvicws in scvcral dihcrcnt
citics, jct lag, worry, and poor slccp had activatcd his illncss, and hc soon
fund himsclf hospitalizcd in a city scvcral hundrcd milcs hom homc.
1j2 M VAi
Hc pullcd a hstml of mcdication bottlcs out of his pockct and put
thcm on thc dcsk in my omcc. "I brought all thcsc ncw mcdicincs, but
I havc to admit, I'vc only bccn taking thc lithium'
I pickcd up thc bottlcs onc by onc. lithium, valproatc, an antipsy-
chotic, an anti- anxicty agcnt, and a slccping pill.
"How long wcrc you in thc hospital I askcd.
"Light days '
"And you wcrc dischargcd on a||this
"That's right. I can't bclicvc I rcally nccd all this. I was so druggcd
whcn my wifc camc to pick mc up, I couldn`t work fr anothcr wcck
and a half. I think this is thc hrst day I'vc fclt safc to drivc'
Craig's illncss had always bccn vcry rcsponsivc to mcdications, it
was hard fr mc to bclicvc that all thcsc mcdications had rcally bccn
ncccssary. How had this happcncd
Whcn I askcd Craig about his trcatmcnt in thc hospital, a sadly
fmiliar story cmcrgcd. a ncw mcdication had bccn addcd to thc
mix almost cvcry othcr day whilc hc was thcrc. Hc was startcd on
thc antipsychotic mcdication as soon as hc was admittcd. Wcll, that
wasn't unrcasonablc, I might havc rccommcndcd that mysclf-fr a
whilc, at lcast. 5ut whcn hc didn`t slccp wcll thc ncxt night, a slccp-
ing pill was addcd. A fcw days latcr, whcn hc mcntioncd that hc had
bccn worricd about his hnanccs latcly, an anti- anxicty mcdication
was addcd. Ahcr a wcck hc told his doctor hc was fccling lcss hypcr
but still not back to his usual sclf-so thc valproatc was addcd to thc
lithium. 5y thc timc hc lch thc hospital, hc wasn't complaining of
mood problcms anymorc bccausc hc was too scdatcd to know wba|
kind of mood hc was in.
"Craig, you know I want you to call thc clinic bcfrc you makc any
changcs in your mcdication on your own,' I said with a smilc. "5ut I
havc to admit, in thc cnd you did cxactly what I would havc rccom-
mcndcd that you do. You ccrtainly don't nccd all this'
Craig smilcd back.

In Craig's casc it was thc doctor who frgot to takc thc long vicw, but
I think it's probably cvcn casicr fr paticnts or thcir fmily mcmbcrs to fll
into thc trap of cxpccting rcsults too guickly .

"Cindy's still having mood swings, Ooctor,' [im said as hc sat down
bcsidc his wifc in thc omcc. " Thc Lamictal isn`t working. Is thcrc somc-
thing clsc wc can try
[im and Cindy wcrc a couplc in thcir thirtics. Thcy had two small
childrcn, and Cindy usually carcd fr hcr attorncy sistcr's littlc boy
during thc day as wcll as hcr own childrcn.
Cindy was tcnsc and guict as hcr husband continucd. "Shc's bccn
on this mcdication fr two wccks now, and things arc no dihcrcnt. Shc
startcd arguing with mc about thc tclcvision bcing too loud thc othcr
night, and whcn I tricd to rcason with hcr, shc pickcd up thc rcmotc
control and thrcw it at mc. This has got to stop'
"What do you think, Cindy I askcd. "Oo you think thc mcdica-
tion has hclpcd any
"Wcll, I' m not surc, but I think maybc it has'
"Wcll, I'm surc it hasn`t,' said [im. " Thc night bcfrc thc rcmotc
incidcnt shc-
"[im,' I said, "it's much too carly to bc surc about anything yct.
I know Cindy's bccn taking thc Lamictal fr scvcral wccks, but shc's
bccn at a mll thcrapcutic dosc fr lcss than onc wcck' I turncd to
Cindy. "What havc you noticcd that makcs you think thc Lamictal
might bc hclping
"Wcll, [im was out of town fr a fcw days last wcck, and so was
my sistcr. I had thc thrcc kids twcnty-fur hours a day thc wholc timc
again. You know how kcycd up I got thc last timc that happcncd'
In fct it had bccn a similar situation that had brought Cindy
into trcatmcnt in thc hrst placc. About thrcc wccks bcfrc our hrst
mccting, Cindy had bccn with thc thrcc boys, six, hvc, and thrcc ycars
old, bccausc of coinciding busincss trips takcn by [im and hcr sistcr.
Shc had nccdcd to call [im and gct him to fly back homc bccausc shc
was bccoming morc and morc irritablc with thc childrcn, snapping at
thcm, slamming doors, starting to fccl out of control.
Thc ncxt wcck shc had comc to scc mc, and as wc talkcd about hcr
past history, it cmcrgcd that shc had cxpcricnccd cpisodcs of dcprcssion
ahcr both of hcr childrcn wcrc born, that shc had had thcsc "hypcr
cpisodcs about oncc a ycar sincc collcgc, and that hcr mothcr had
suhcrcd hom "mood swings and alcoholism. A diagnosis of bipolar II
or pcrhaps a "soh bipolar disordcr sccmcd likcly, and wc dccidcd on a
trial of a mood stabilizcr.
"Thc kids just didn`t gct to mc this timc,' Cindy continucd. "Iirst
I thought thcy wcrc bcing on thcir bcst bchavior bccausc of what had
happcncd that last timc, and maybc thcy wcrc fr an hour or so. 5ut by
cvcning I rcalizcd that thcy wcrc rcally about as activc as thcy usually
arc, and that thcrc was somcthing dihcrcnt about mc. I wasn`t as, you
know, scnsitivc. Scvcral timcs now I'vc noticcd that I can handlc things
1jq M VAi
"ot thc othcr night,' [im chimcd in. `+m not noticing much dif-
"Wcll, maybc [im`s right,' Cindy wcnt on. "Maybc you could givc
mc somcthing fr thc timcs whcn I'm fccling rcally strcsscd Somc
Valium or Xanax I ncvcr uscd . . . I don`t know what to call thcm-
ncrvc pills And I'm surc I wouldn`t nccd thcm ohcn'
"I don't think wc should add morc mcdication until wc'rc surc
you'rc gctting thc maximum bcncht hom thc onc you'rc on. And hom
what you'rc tclling mc, I think that's bcginning to happcn,' I said. "Thc
fct that you'vc ncvcr fclt thc nccd fr tranguilizcrs bcfrc makcs mc
think that thc bipolar disordcr cxplains all your symptoms and nccds
to bc thc fcus of our attcntion. It's absolutcly too carly to cxpcct thc
Lamictal to havc had its mll chcct. Lct's talk about this a bit morc'

Cindy and [im arc vcry anxious fr Cindy's symptoms to stop. Who can
blamc thcm 5ut to givc up on a mood stabilizcr bccausc it hasn't complctcly
controllcd cvcry symptom so soon is folish. It's unlikcly that anothcr would
work any fstcr-and it might not cvcn work as wcll, in which casc Cindy
would bc right back to sguarc onc ahcr anothcr couplc of wccks.
Cindy's situation also scrvcs to illustratc anothcr principlc of trcatmcnt.
rcmcm|cr|bcd|aycs|s.If thc thrcc most important words in thc rcal cstatc
busincss arc |cca||cn, |cca||cn, and |cca||cn, thcn thc thrcc most important
words in mcdicinc arc d|ayncs|s, d|aycs|s, and d|aycs|s. 5ccausc wc havc
so many chcctivc mcdications, it can bc tcmpting to considcr prcscribing
onc cvcn though thcrc isn`t rcally a justihcation fr it bascd on thc paticnt's
undcrlying diagnosis. Thcrc was a tcndcncy at onc timc in psychiatry to scc
mcdications as sym|cma||c |rca|mcn|s. This mcans picking a mcdication
and making thc dccision to usc it bascd on idcntihcation of sym|cms, not
undcrlying d|aycscs. Cindy wants to try anothcr mcdication fr "strcss -
that is, fr fccling tcnsc and irritablc. 5ut thc symptoms of our working
diagnosis, bipolar disordcr, includc pcriods of tcnsion and irritability. If
Cindy's poor strcss tolcrancc is a symptom of hcr mood disordcr, and shc
takcs an anti- anxicty mcdication to covcr it up rathcr than gctting morc
intcnsivc trcatmcnt of thc mood disordcr, shc'll cnd up taking a mcdication
shc docsn`t rcally nccd fr a symptom that isn't going to gct much bcttcr bc-
causc thc undcrlying problcm, bipolar disordcr, isn't bcing propcrly trcatcd.
Insomnia is a similar symptom, vcry commonly a symptom of thc mood
disordcr but all too commonly trcatcd with slccping mcdications as i f i t wcrc
an isolatcd symptom.
VAi PPVLLHS 1i 1PL1V 11SLV1V M 1jj
Lvcry oncc in a whilc I scc a paticnt with bipolar disordcr who has rcad a
magazinc articlc about attcntion- dchcit hypcractivity disordcr and rcgucsts
mcdication fr AOHO. Somc of thc symptoms of AO HO-likc impulsiv-
ity, impaticncc, fst, disorganizcd thinking, and poor conccntration-arc,
of coursc, also sccn in bipolar paticnts. Thcsc arc distrcssing symptoms that
dcscrvc attcntion, but thcy dcscrvc thc right kind of attcntion. If thcy arc
an cxprcssion of thc mood changcs of bipolar disordcr, thcn mcdication fr
AOHO won`t hclp. [In fct, thc mcdications uscd to trcat AOHO, stimulants
and antidcprcssants, can makc things worsc. )
Making a diagnosis is thc proccss of idcntifying thc onc discasc that can
cxplain all thc paticnt's symptoms. This is a variation of thc scicntihc princi-
plc callcd ccam`s razor, namcd ahcr William of ccam [ or ckham), thc
mcdicval thcologian- philosophcr crcditcd with coining this principlc. Thc
simplcst cxplanation fr a phcnomcnon is always prcfcrablc to a morc com-
plcx onc and is most likcly to bc corrcct. bviously a paticnt may havc two
dihcrcnt disordcrs that rcguirc two dihcrcnt trcatmcnt approachcs. 5ut if
all thc paticnt's symptoms can bc undcrstood as cxprcssions of cncdisordcr,
trcating that onc will likcly allcviatc all thc symptoms.
I scc this problcm of multiplc diagnoscs and symptomatic trcatmcnts
cvcn morc commonly in dcprcsscd paticnts. In dcprcssion, anxicty and in-
somnia can bc thorny and uncomfrtablc cxprcssions of thc mood disor-
dcr-and physical symptoms can bc as wcll, cspccially in thc cldcrly. I havc
sccn cldcrly paticnts taking antidcprcssant mcdications [ ohcn at an inadc-
guatc dosc) who arc also taking slccping pills, tranguilizcrs, anti- inflamma-
tory and pain mcdications fr arthritis pain, stool sohcncrs and laxativcs
fr constipation, and somctimcs somc vitamins and tonics thrown in fr
good mcasurc [pcrhaps bccausc of complaints of "low cncrgy) . All thcsc
problcms arc symptoms of dcprcssion [ cvcn thc arthritis pain, bccausc dc-
prcsscd paticnts bccomc morc distrcsscd by painml problcms likc arthritis) ,
but somctimcs it's hard to scc thc frcst fr thc trccs. 5cfrc you know it,
thc paticnt is taking a dozcn or so dihcrcnt mcdications fr all thc dihcrcnt
symptoms of dcprcssion, and thc discasc that undcrlics thcm all, a mood
disordcr, has bccn misscd. I t i s an amazing cxpcricncc t o scc all thcsc symp-
toms that havc not bccn hclpcd by pcrhaps a dozcn mcdications disappcar
ahcr a coursc of clcctroconvulsivc thcrapy in an cldcrly paticnt.
This lcads mc to anothcr principlc. C7sbcu|dnc||ca|rca|mcn|c}|as|
rcscr|}cr ||c|ard|scrdcr. LCT should bc considcrcd whcncvcr symptoms
arc vcry scvcrc, or whcn thcy arc scvcrc cnough to intcrfcrc with work and
fmily lifc and havc gonc on fr an cxtcndcd pcriod of timc. Somc gcri-
1 M VAi
atric psychiatrists rccommcnd LCT as thc {rs|-||nc |rca|mcn| fr scrious
mood- disordcr symptoms in thc cldcrly. If thc paticnt is having symptoms
day ahcr day, has bccn on mcdical lcavc hom work fr wccks, and is still
not gctting rclicf hom his mcdication, it's timc to scriously considcr LCT.
Whcn symptoms arc disabling, LCT should probably bc considcrcd ahcr
thc filurc of thc hrst mcdication, not ahcr thc filurc of thc sccond or third
or furth.
Pcrhaps thc most uncxpcctcd hnding to comc out of thc STLP- 5O was
thc surprising lack of cvidcncc that antidcprcssant mcdications arc hclpml in
trcating bipolar disordcr. nc of thc studics within thc STLP- 5O comparcd
dcprcsscd paticnts trcatcd with a mood stabilizcr plus an antidcprcssant [ci-
thcr scrtralinc or bupropion) with paticnts trcatcd with a mood stabilizcr
and a placcbo. Thc main paticnt-outcomc goal fr this part of thc study was
"durablc rccovcry hom dcprcssion, dchncd as maintaining a normal mood
fr at lcast cight wccks. Lsing this standard, antidcprcssants wcrc no morc
chcctivc in thcsc bipolar paticnts than thc placcbo [thc paticnts taking thc
antidcprcssant with thcir mood stabilizcr did no bcttcr than thosc who took
only a mood stabilizcr) . ot only that. whcn somc sccondary mcasurcs wcrc
asscsscd, thcrc was thc suggcstion that thc paticnts on mood stabilizcr alonc
did somcwhat |c||crthan thc paticnts who took an antidcprcssant. Ior cx-
amplc, it appcarcd that dcprcsscd paticnts with bipolar II disordcr actually
did a bit bcttcr w||bcu|thc antidcprcssant. Iurthcrmorc, as a fllow-up to
thc placcbo- controllcd study, thc paticnts who d|d rccovcr and who wcrc
taking thc antidcprcssant with thcir mood stabilizcr wcrc dividcd into two
groups. onc group continucd on both mcdications, and thc othcr group
stoppcd taking thc antidcprcssant. Again, thc group that stoppcd taking thc
antidcprcssant did just as wcll as thosc who did not. taking an antidcprcs-
sant did not kccp paticnts wcll longcr and did not dclay a rclapsc, comparcd
with taking a mood stabilizcr alonc. Although it did not rcach thc lcvcl of
statistical signihcancc, thcrc was also thc suggcstion that paticnts who had
rapid- cycling symptoms [scvcral cpisodcs of mania or dcprcssion in a ycar)
had a rclapsc of dcprcssion sccncrthan thosc who stoppcd taking thc an-
tidcprcssant. that is, continuing on an antidcprcssant incrcascd thc risk of
gctting dcprcsscd. Talk about countcrintuitivc|
It has bccn known fr many ycars that antidcprcssants can triggcr manic
or mixcd symptoms in bipolar paticnts. Clinicians havc also long suspcctcd
that antidcprcssant mcdications incrcasc cycling in bipolar paticnts, causing
thcm to havc morc cpisodcs of dcprcssion and manic or mixcd symptoms.
VAi PPVLLHS 1i 1PL1V 11SLV1V M 1j,
Thc STLP-5O appcars to rcinfrcc both of thcsc imprcssions. Howcvcr,
cvcry psychiatrist carcs fr paticnts with bipolar disordcr who can safcly takc
an antidcprcssant and who rcguirc it to stay wcll.
So what should wc concludc about thc usc of antidcprcssant mcdica-
tions in bipolar paticnts I think it's fir to say that antidcprcssants should
bc uscd with cxtrcmc caution in paticnts with bipolar disordcr, and that an
antidcprcssant should bc discontinucd as soon as possiblc ovcr thc longcr
tcrm of trcatmcnt. Antidcprcssants should bc stoppcd immcdiatcly if thc
paticnt dcvclops insomnia or fccls ovcractivatcd or "wircd ahcr shc starts
taking an antidcprcssant. I havc had paticnts dcscribc this as fccling "anx-
ious,' and whilc it may bc a fccling that is similar to anxicty, whcn I scc a
bipolar paticnt taking an antidcprcssant who rcports scvcrc "anxicty,' I havc
a vcry low thrcshold fr stopping thc antidcprcssant.
Somctimcs thcrc don`t sccm to bc any immcdiatc untoward chccts hom
starting an antidcprcssant, but it may bccomc clcar ovcr timc that thc pa-
ticnt is cycling morc ohcn. If, in thc months [or cvcn ycars) ahcr a paticnt
starts taking an antidcprcssant, hc noticcs ncw mood symptoms, such as
mixcd symptoms or problcms with "ragcs fr thc hrst timc, thc continucd
usc of thc antidcprcssant should bc scriously gucstioncd.

Iinally, I can`t strcss cnough that cvcry||c|ara||cn|nccdssycbc|bcr-
ay at onc point or anothcr. Scvcral wccks or months of counscling is ab-
solutcly csscntial ahcr thc diagnosis and initiation of trcatmcnt fr bipolar
disordcr. [ust as a pcrson with diabctcs nccds to fllow dictary rccommcn-
dations to gct thc bcst control of hcr glucosc lcvcls, and a hip-hacturc pa-
ticnt nccds physical thcrapy fr optimal mnctioning, pcrsons with bipolar
disordcr nccd psychothcrapy at timcs to havc thc bcst possiblc control of
thcir mood symptoms.
Psychothcrapy is onc intcrvcntion fr thc dcprcssion of bipolar disordcr
that I can conhdcntly statc docs nc|havc any risk of triggcring manic symp-
toms or incrcascd cycling. Many pcrsons with bipolar disordcr go through a
pcriod of dcprcssion ahcr thcy rccovcr hom a pcriod of mania or hypoma-
nia. It can bc vcry tcmpting to think about using an antidcprcssant to dcal
with this problcm. Ior thc rcasons notcd abovc, howcvcr, this is not usually a
good idca. Ouring somc pcriods of bipolar dcprcssion, thc intcrvcntion that
nccds to bc startcd, or givcn at a highcr "dosc,' is psychothcrapy.
1j M VAi
A H 1
.JJ.J^ L.\^^
In this group of chaptcrs wc'll cxplorc scvcral variations on thc thcmc
of bipolar disordcr. Wc'll look hrst at how thc coursc and symptoms of
thc illncss can dihcr in childrcn and adolcsccnts and thcn notc thc dif-
fcrcnccs in symptoms bctwccn mcn and womcn [with spccial attcntion
to prcmcnstrual mood symptoms, thc challcngc of postpartum mood
disordcrs, and thc dilcmmas fccd by womcn who havc thc illncss
during thcir childbcaring ycars) .
Chaptcr i , dcals with thc complicatcd rclationships bctwccn bi-
polar disordcr and substancc abusc. Individuals with bipolar disordcr
sccm to bc cspccially vulncrablc to substancc-abusc disordcrs, so much
so that it's rcasonablc to think of chcmical dcpcndcncy as a compli-
cation of thc illncss. Thc symptoms of substancc abusc and of bipolar
disordcr can bccomc so intcrtwincd that it is impossiblc to hgurc out
which is which. Wc'll look fr a way out of this conmsion and dis-
cuss thc trcatmcnt approachcs that work in such cascs. It's cxtrcmcly
important to conhont chcmical dcpcndcncy hcad on, bccausc rcscarch
shows that alcoholism and drug abusc arc ohcn }a|a|complications of
bipolar disordcr.
In thc subscgucnt chaptcrs, wc'll go hom onc cxtrcmc to thc othcr
as fr as causcs and conncctions arc conccrncd, looking hrst at somc
vcry concrctc scicntihc issucs and thcn at somc vcry abstract, almost
philosophical oncs. In chaptcr iwc'll lcarn about our body's biolog-
ical clock and thc rclationship bctwccn mood and thc slccp cyclc and
about thc scasonal cyclcs somc pcrsons with bipolar disordcr havc. In
chaptcr i;wc'll cxplorc an arca of intcnsc intcrcst to bipolar paticnts
and thcir fmily mcmbcrs. thc gcnctics of bipolar disordcr. Chaptcr i8
considcrs othcr aspccts of bipolar biology. how mood disordcrs can bc
causcd by mcdical illncsscs, somc of thc ways wc arc ablc t o litcrally
look at bipolar disordcr in thc mnctioning brain, and, hnally, thc pos-
siblc conncctions bctwccn bipolar disordcr and viruscs.
Thcn, ahcr wc'vc hnishcd talking about OA molcculcs and
chromosomcs and brain chcmicals, wc'll lcavc thc laboratory and go
into thc artist's studio, to cxaminc somc of thc intriguing conncctions
bctwccn this tcrriblc illncss and artistic gcnius and crcativity.
10 M NV11LiS, L\SS, i1 LLiiL1LiS
L M A 1 H J
1O1d1 I1SO1UO1 1D LD11U1OD
rarc in young pcoplc, cvcn though rcscarch data on adults indicatcd that thc
hrst appcarancc of thc symptoms of thc illncss usually occurrcd bcfrc agc
twcnty. [Lmil Kracpclin fund that thc highcst numbcr of "hrst attacks of
manic- dcprcssivc illncss occurrcd bctwccn thc agcs of hhccn and twcnty.)
Pcrhaps bccausc of a rcluctancc to diagnosc childrcn with an illncss known
to bc a lifclong problcm and thc unwillingncss to prcscribc fr childrcn thc
powcrml mcdications uscd to trcat its symptoms, bipolar disordcr in young
childrcn rcccivcd littlc attcntion hom rcscarchcrs until guitc rcccntly.
Rcccnt rcscarch suggcsts that bipolar disordcr is much morc common
in young pcoplc than prcviously rccognizcd. In zoiithc World Hcalth rga-
nization cstimatcd that pcdiatric bipolar disordcr is thc furth lcading causc
of disability in adolcsccnts agcd hhccn to ninctccn worldwidc, accounting
fr a total of pcrccnt of disability in this agc rangc.
Ior a long timc, thc trcatmcnt of childrcn and adolcsccnts with bipolar
symptoms consistcd mostly of improviscd variations on adult trcatmcnts.
Iortunatcly, this too is changing, thcrc is now guitc a bit of rcscarch availablc
to guidc thc clinician in crahing a trcatmcnt plan fr young paticnts with
bipolar disordcr.
Lvcn vcry young childrcn can havc bipolar symptoms . In onc study that
lookcd at such symptoms in thc pcdiatric [undcr cightccn) agc rangc, ncarly
onc-third of thc paticnts wcrc youngcr than twclvc, and thc avcragc agc of
onsct fr thcsc young bipolar paticnts was cight and a half. ' This samc rc-
Tzeiri - i Comparison of adult and pcdiatric bipolar disordcr
Initial episode.
Episode tye.
Functioning between episodes.
Major depression
Rapid cycling, mixed
Chronic, continuous
Poor continuous cycling)
Discrete episodes
scarch is also shcdding light on why psychiatrists uscd to think pcdiatric
bipolar disordcr was a rarc diagnosis . although adolcsccnts with bipolar dis-
ordcr havc symptoms similar to thosc of adults, bipolar disordcr in young
childrcn can appcar rathcr dihcrcnt [tablc i - i) .
It appcars that whcn bipolar disordcr occurs i n young childrcn [bcfrc
pubcrty) , it is a morc scvcrc frm of thc illncss. Pcrhaps this is bccausc chil-
drcn who dcvclop symptoms of bipolar disordcr at so young an agc havc a
hcavicr gcnctic "loading'' fr mood disordcrs than do pcoplc whosc symp-
toms bcgin latcr. 5ipolar childrcn ohcn havc morc individuals with mood
disordcrs i n thcir fmilics than adult- diagnosis bipolar paticnts, fr many of
thcsc childrcn, mood disordcrs cxist on both sidcs of thc fmily.' Anothcr
dihcrcncc bctwccn childhood- and adult-onsct bipolar disordcr is that in-
stcad of mania or hypomania, a major dcprcssion is hcgucntly thc hrst sign
of thc disordcr in childrcn. Scvcral studics indicatc that 2O to o pcrccnt of
young childrcn with major dcprcssions dcvclop manic symptoms latcr in
lifc. '
5ut thc most striking dihcrcncc bctwccn childhood- onsct and latcr-
onsct bipolar disordcr is thc coursc of thc illncss. Pcdiatric bipolar disor-
dcr is a much morc continuous illncss than adult bipolar disordcr. In most
adults thc illncss appcars in discrctc cpisodcs of dcprcssion or mania, and
thc symptoms go into rcmission fr months or ycars at a timc. Childrcn, in
contrast, ohcn havc long pcriods of continuous rapid cycling. Thcsc childrcn
somctimcs cyclc bctwccn dcprcssion and mania scvcral timcs a day, having
a laughing ht onc momcnt and talking about wanting to shoot thcmsclvcs
thc ncxt.' nc study of bipolar disordcr in thc pcdiatric agc rangc dcscribcd
childrcn who had morc than onc hundrcd minimanias in a ycar, mood cp-
isodcs that lastcd only a day or two. In this study, nonc of thc rcscarch sub-
jccts undcr thc agc of ninc had a singlc mood cpisodc lasting two wccks or
morc as his only cpisodc. Ior thcsc childrcn a complcx pattcrn of hcgucnt,
short cpisodcs was thc rulc, not thc cxccption. `
12 M NV11LiS, L\SS, i1 LLiiL1LiS
Symptoms ot Pcdatrc BpoIar sordcr
Ocprcssion is comparativcly casy to spot in childrcn. thc wccpy, listlcss,
and lcthargic child is guickly rccognizcd as a sick child. 5ut how do you
distinguish hypomanic or manic bchavior in a child hom thc boistcrousncss
and high cncrgy of normal childrcn An cvcn morc dimcult task is to dihcr-
cntiatc manic symptoms hom thc hypcractivity and "can`t sit still picturc of
attcntion-dchcit hypcractivity disordcr [AOHO) .
Thc dihcrcntiation is possiblc if closc attcntion i s paid t o changcs in
mood. Childrcn with AOHO arc hypcractivc but don't havc thc cxpansivc,
grandiosc mood of mania. Thc child with AOHO may disrupt a classroom
with clowning around and rcstlcssncss, but a manic child may tcll thc tcachcr
that thc lcssons arc bcing taught incorrcctly and try to takc ovcr thc class.
Thc manic child caught taking things that bclong to somconc clsc may say
that it's wrong fr othcr pcoplc to stcal but not fr hcr. Thc manic child may
bc convinccd that hc is dcstincd fr a brilliant carccr as a doctor or a lawycr
dcspitc filing ncarly cvcry subj cct in school. Thc child may bclicvc that hc is
on thc vcrgc of bccoming a rock star dcspitc bcing unablc to play a musical
ormal childrcn, of coursc, fntasizc in similar ways about thcir mturc,
but thcy arc ablc to scparatc thcir fntasics hom rcality and apply thcmsclvcs
to school work and fllow thc rulcs at homc. Manic childrcn, convinccd of
thc rcality of thcir grandiosc idcas, spcak and act bascd on thc bclicf that thc
usual rulcs and rcguircmcnts don't apply to thcm.
Manic childrcn jump hom topic to topic in thcir spccch pattcrns, arc
dimcult to intcrrupt, and complain that thcir thoughts arc moving too fst.
Hypcrscxuality is a symptom in oldcr childrcn, who may bccomc scxually
promiscuous or masturbatc cxccssivcly, thcy may suddcnly start using scx-
ual profanity or say that a tcachcr or a fmous pcrson is in lovc with thcm.
Spcnding sprccs may takc thc frm of ordcring itcms ovcr thc phonc using
i-8ooand i- oonumbcrs .
Vcry young childrcn may havc manic cxaggcrations of thc normal mag-
ical thinking of childhood but will act on this thinking instcad of using it
as a basis fr play. ormal childrcn may imaginc that thcy can fly and may
run through thc back yard "flapping thcir arms likc thc wings of a bird or
making airplanc noiscs. A manic child undcr thc influcncc of thc dclusion
that shc has bccomc an angcl or a supcrhcro may jump out of a window or
oh thc roof of a housc. Thc symptoms of bipolar disordcr in childrcn can bc
cvcry bit as dcadly as thcy arc in adults.
Whcn a young pcrson dcvclops scrious dcprcssion, how can wc tcll
whcthcr hc might bc having thc hrst cpisodc of what will turn out to bc bi-
polar disordcr Although it's impossiblc to know fr surc, thcrc arc somc in-
1PL1V 11SLV1V 1i LH111Vi i1 1L1SLiS M 1j
dicators that sccm to bc firly rcliablc. In onc study, rcscarchcrs invcstigatcd
a group of sixty adolcsccnts, agcd thirtccn to sixtccn ycars, who had bccn
hospitalizcd fr maj or dcprcssion ovcr thc coursc of thrcc to fur ycars, thc
purposc was to scc whcthcr any particular clinical variablcs might prcdict
which of thcm would cvcntually dcvclop a bipolar coursc of illncss zo pcr-
ccnt of thc group cvcntually did) . Statistical analyscs showcd that bipolarity
was prcdictcd by a dcprcssivc symptom clustcr that includcd rapid symptom
onsct, a slowcd- down, "rctardcd typc of dcprcssion, and psychotic fcaturcs
[hallucinations or dclusions) . A fmily history of mood disordcrs [bipolar
disordcr or maj or dcprcssion) in many fmily mcmbcrs and through suc-
ccssivc gcncrations was also a prcdictor, as was a history of thc adolcsccnt
dcvcloping hypomanic symptoms whcn shc took antidcprcssant mcdica-
tions-a clinical indicator that turncd out to bc ioopcrccnt accuratc in prc-
dicting bipolar disordcr in this group. "
BpoIar sordcr and Attcnton-chct
Hypcractvty sordcr
Psychiatrists usc thc tcrm ccmcr||d||yto dcscribc two scparatc condi-
tions or illncsscs that hcgucntly occur togcthcr in thc samc paticnt. Thcrc is
a high dcgrcc of comorbidity bctwccn AOHO and mood disordcrs, in somc
studics as high as pcrccnt.
Childrcn and young adolcsccnts with bipolar disordcr ohcn do not havc
thc discrctc pcriods of clcvatcd, usually cuphoric mood sccn in oldcr ad-
olcsccnts and adults. Rathcr, cxtrcmc irritability and prolongcd aggrcssivc
tcmpcr tantrums callcd "ahcctivc storms arc common, and thc abnormal
mood is ongoing and continuous rathcr than cpisodic as in oldcr individu-
als. Oistractibility, impulsivity, hypcractivity, and "mood swings arc symp-
toms of both AOHO and mania. Ior thcsc rcasons, thc diagnosis of both
mood disordcrs and AOHO is dimcult in young pcoplc, and thc rclation-
ships bctwccn thc two diagnoscs arc, at this point, poorly undcrstood.
It i s possiblc to dihcrcntiatc bctwccn thc symptoms of AOHO and bi -
polar disordcr i n many young pcoplc, but thcrc arc somc individuals who
sccm to havc both disordcrs simultancously. In onc study of childrcn who
had alrcady bccn diagnoscd with AOHO, zi pcrccnt wcrc also fund to
mcct thc diagnostic critcria fr bipolar disordcr by agc hhccn-that is, thcy
sccmcd to havc both disordcrs. This suggcsts that, in somc youngstcrs at
lcast, AOHO symptoms may in fct bc carly signs of bipolar disordcr. Thc
AOHO childrcn who cvcntually dcvclopcd bipolar symptoms had morc sc-
vcrc symptoms and morc disturbcd bchaviors than thosc who did not. Lvcn
morc of thcsc AOHO childrcn with morc scvcrc symptoms mct thc critcria
fr a diagnosis of maj or dcprcssion. by agc clcvcn, z pcrccnt had maj or
1q M NV11LiS, L\SS, i1 LLiiL1LiS
dcprcssion, and by agc hhccn, q pcrccnt had bccn diagnoscd with major
dcprcssivc disordcr.
How do wc undcrstand thc childrcn whosc AOHO sccms to dcvclop
into bipolar disordcr Oid thcy rcally havc AOHO symptoms in thc hrst
placc, or docs vcry- carly- onsct bipolar disordcr mimic AOHO in its carly
stagcs Arc AOHO and carly- onsct bipolar disordcr two scparatc illncsscs
that sharc similar symptom picturcs but havc dihcrcnt causcs Can AOHO
dcvclop into bipolar disordcr If so, how And what do wc makc of thc cx-
trcmcly high comorbidity bctwccn AOHO and mood disordcr Thcsc gucs-
tions arc, as yct, unanswcrcd.
It has bccn suggcstcd that thc link bctwccn thc two disordcrs may bc
gcnctic. Whcn fmily mcmbcrs of AOHO childrcn arc studicd, thcy arc
fund to havc high ratcs of mood disordcrs. Childrcn of parcnts with mood
disordcrs havc high ratcs of AOHO. Thc rcscarchcrs studying thc group of
young pcoplc with AOHO dcscribcd abovc invcstigatcd thc prcvalcncc of
mood disordcrs in fmily mcmbcrs. Thcy fund that rclativcs of childrcn
with both AOHO and bipolar disordcr wcrc hvc timcs as likcly to havc bi-
polar disordcr thcmsclvcs as fmily mcmbcrs of childrcn with only AOHO.
Thcy also fund high ratcs of major dcprcssion among thc rclativcs of thc
childrcn with AOHO and bipolar disordcr. Thc rcscarchcrs spcculatc that
AOHO with bipolar disordcr is a particular subtypc of thc illncss. ' r pcr-
haps thcsc arc two scparatc illncsscs that happcn to bc inhcritcd togcthcr
hcgucntly bccausc thc gcncs that causc thcm arc locatcd ncar onc anothcr
on thc chromosomc and thus arc usually inhcritcd togcthcr. Thc only thing
about this mystcrious conncction that wc arc rcally surc of is that much rc-
scarch in thc arca rcmains to bc donc.
Trcatmcnt and Prognoss
Somc studics havc indicatcd that lithium is chcctivc in childrcn, but it
is firly clcar that it is not as chcctivc in childrcn as in adults. If complicatcd
rapid- cycling bipolar disordcr is indccd thc rulc in carly- onsct bipolar dis-
ordcr, thcn lithium rcsistancc should not bc a big surprisc. similar typcs of
bipolar symptoms sccm rclativcly lithium- rcsistant in adults, too. Pcdiatric
lithium doscs arc, of coursc, lowcr than adult doscs, but thc chcctivc thcr-
apcutic rangc fr lithium in thc bloodstrcam whcn it docs work sccms to
bc about thc samc in childrcn as in adults. [ Rcmcmbcr that thc thcrapcutic
rangc in thc bloodstrcam is a mcasurc of lithium conccntration. 5ccausc
childrcn havc a smallcr total blood volumc than adults, a lowcr dosc of lith-
ium fr a child will rcsult in thc samc conccntration in thc bloodstrcam. )
Cctting rcgular blood tcsts donc is, of coursc, morc challcnging with chil-
drcn than with adults, but givcn thc toxicity of lithium, blood- lcvcl tcsts arc
1PL1V 11SLV1V 1i LH111Vi i1 1L1SLiS M 1j
if anything cvcn morc important in childrcn. Scvcral studics havc bccn donc
using mcthods that avoid thc nccdlcs and dctcrminc lithium lcvcls hom sa-
liva rathcr than hom blood, but thc rcsults havc bccn disappointing, and so
fr now thcsc littlc paticnts must, unfrtunatcly, havc blood tcsts.
Scvcral studics havc indicatcd that valproatc is chcctivc fr somc young
childrcn with bipolar disordcr, and somc havc suggcstcd that it is morc cf-
fcctivc than lithium in this agc rangc. Thcrc is now substantial rcscarch sup-
porting thc usc of atypical antipsychotic mcdications fr pcdiatric bipolar
disordcr. Thcsc agcnts appcar to bc morc chcctivc than lithium or anticon-
vulsant mood stabilizcrs in young paticnts. 5ccausc of thcsc issucs, a combi-
nation of mcdications is commonly rcguircd to kccp pcdiatric bipolar- dis-
ordcr symptoms undcr control. '"
Thc combination of AOHO and bipolar disordcr sccms to bc cspccially
dimcult to trcat, and in thosc cascs cspccially, combinations of mcdications
arc ohcn ncccssary. In a study of adolcsccnts bcing trcatcd with lithium fr
a manic cpisodc, a comparison was madc bctwccn thc trcatmcnt rcsponsc
in adolcsccnts with and without a history of childhood-onsct AOHO. Thc
adolcsccnts with thc AOHO history took signihcantly longcr to gct bcttcr
on lithium than thc adolcsccnts with no history of AOHO symptoms . This
sccms to bc mrthcr cvidcncc that thc combination of AOHO and bipolar
disordcr may bc a subtypc of illncss and that it is cspccially challcnging to
trcat. ' '
Many clinicians rccommcnd avoiding stimulant mcdications complctcly
in young pcrsons with bipolar disordcr. Thc samc gocs fr somc othcr trcat-
mcnts fr AOHO, most notably antidcprcssants. Thc problcm hcrc is thc
samc as with stimulant mcdications. thc possibility of prccipitating mania
in a prcdisposcd youngstcr. Anothcr mcdication uscd to trcat AOHO, ato-
moxctinc [Strattcra), has also bccn rcportcd to prccipitatc mania. Whcn it
was givcn to an clcvcn-ycar- old boy who had bccn diagnoscd with AOHO,
had a fmily history suggcstivc of bipolar disordcr, and had cxpcricnccd
manic-typc symptoms hom antidcprcssants, hc dcvclopcd scvcrc manic
symptoms. ' '
Clonidinc [Cataprcs) and guanfcinc [Tcncx), mcdications uscd to trcat
high blood prcssurc in adults, havc bccn fund to bc hclpml in AOHO.
Whcrcas stimulant mcdications hclp with inattcntion but arc not vcry hclp-
ml fr impulsivity and hypcractivity, clonidinc and guanfcinc sccm to bc
chcctivc in rcducing thcsc symptoms. Thcrc i s also vcry prcliminary cvi-
dcncc that mcdications that ahcct thc ncurotransmittcr acctylcholinc may
bc hclpml fr thc symptoms of AOHO. Tacrinc [ Cogncx) and doncpczil
[Ariccpt), two mcdications with this thcrapcutic mcchanism that arc uscd
to trcat Alzhcimcr's discasc in thc cldcrly, havc bccn rcportcd to bc hclpml
1 M NV11LiS, L\SS, i1 LLiiL1LiS
fr thc trcatmcnt of AOHO. ' ' Thcsc altcrnativcs may bc safcr fr youngstcrs
with bipolar disordcr who nccd additional trcatmcnt fr AOHO.
How is normal psychological dcvclopmcnt in childrcn ahcctcd by bi-
polar disordcr Rclationships with fmily mcmbcrs arc ohcn straincd fr
thcsc paticnts, as arc rclationships with thcir pccrs. Thcir cducational dc-
vclopmcnt incvitably suhcrs as wcll. Clcarly, attcntion to thc psychological
nccds and thc spccial cducational rcguircmcnts of thcsc childrcn is vitally
important to minimizc thc chccts of thc illncss on thcir psychological dc-
vclopmcnt. Thus, pcrhaps cvcn morc than in adults, counscling and thcrapy
must bc a high priority whcn dcvcloping trcatmcnt plans fr childrcn with
bipolar disordcr.
Oocs carlicr onsct of bipolar symptoms prcdict a stormicr coursc of
illncss latcr on As notcd prcviously, childrcn hcgucntly havc continuous
rapid cycling and mixcd symptoms . Oocs thc illncss takc on thc morc usual
adult pattcrn of discrctc cpisodcs as thcsc childrcn agc If so, arc thc cpi-
sodcs morc hcgucnt than in pcrsons with latcr- onsct illncss Thc jury is
still out on this gucstion, rcscarch rcsults arc lacking. 5ut at lcast onc small
study shows that bipolar disordcr in young pcrsons can indccd bc a dimcult
illncss to managc. In this study, hhy- fur adolcsccnts who wcrc admittcd to
a univcrsity hospital with a diagnosis of bipolar I disordcr wcrc fllowcd fr
hvc ycars. '' f thcsc youngstcrs, ncarly half had a rclapsc, and about half
of thcsc had two or morc cpisodcs during thc hvc ycars of thc study. This
study was donc on paticnts who nccdcd to bc admittcd to thc hospital, and
so it is biascd toward sickcr paticnts . This typc of rcscarch problcm is callcd
asccr|a|nmcn| ||as: thc rcsults of thc study may bc skcwcd bccausc of thc
mcthod uscd to gathcr paticnts fr thc study. In this casc, sincc paticnts who
wcrc not ill cnough to nccd hospitalization would not havc madc it into thc
study, thc study group may not bc rcprcscntativc of all pcdiatric bipolar I pa-
ticnts. cvcrthclcss, thcsc rcsults would sccm to indicatc that at lcast somc
of thcsc young paticnts arc cspccially pronc to rclapsc and so nccd carcml
5ut as to thc longcr coursc of bipolar disordcr that bcgins in childhood,
thcrc is practically no infrmation. Is thc coursc of illncss dihcrcnt at agc
thirty or frty dcpcnding on whcthcr it startcd at agc tcn or at twcnty Thcrc
arc no dchnitivc answcrs to this sort of gucstion fr now.
Scvcral tasks lic ahcad fr thosc rcscarching bipolar disordcr in chil-
drcn. Iirst will bc to improvc upon thc diagnostic proccss and hnd out how
to bcttcr scparatc bipolar [cspccially manic) symptoms hom othcr simi-
lar diagnostic picturcs-cspccially attcntion- dchcit hypcractivity disordcr.
Clarifying thc rclationship bctwccn bipolar disordcr and AOHO will bc a
vcry instructivc arca of rcscarch fr othcr rcasons as wcll and will surcly
1PL1V 11SLV1V 1i LH111Vi i1 1L1SLiS M 1,
lcad to bcttcr undcrstanding of and trcatmcnts fr both disordcrs . Morc rc-
scarch to dctcrminc which of thc availablc trcatmcnts fr bipolar disordcr
work bcst fr childrcn and adolcsccnts is also nccdcd, as arc long- tcrm fl-
low- up studics to scc if pcdiatric- onsct bipolar disordcr looks dihcrcnt hom
latc- adolcsccnt-onsct bipolar disordcr as thc paticnt grows to adulthood.
1 P NV11LiS, L\SS, i1 LLiiL1LiS
L M A 1 H 1
YOHOD W11D 1O1d1 I1SO1UO1t
hom bipolar disordcr, thc hormonal changcs that accompany mcnstruation
and prcgnancy ahcct thc coursc of bipolar disordcr in womcn and dcscrvc
spccial attcntion, as do somc pattcrns of symptoms morc ohcn cxpcricnccd
by womcn than mcn with bipolar disordcr. In addition, mcdication usc
during prcgnancy and whilc brcast- fccding rcguircs carcml considcration.
Symptom Hcrcnccs n Womcn
f thc various dihcrcnccs bctwccn thc gcndcrs in thc coursc of illncss
and symptoms of bipolar disordcr, thc grcatcr incidcncc of rapid cycling
in womcn is thc bcst documcntcd. 1 rcvicw articlc on bipolar disordcr in
womcn lookcd at tcn studics involving scvcral hundrcd pcrsons with rapid-
cycling bipolar disordcr and fund that q pcrccnt of thc rapid- cycling pa-
ticnts wcrc fcmalc. ' Thus, thc ratio of womcn to mcn with rapid- cycling dis-
ordcr is j .I.
Scvcral rcasons havc bccn proposcd fr this dihcrcncc. Sincc thyroid
problcms havc bccn associatcd with rapid cycling in bipolar disordcr, and
sincc womcn arc morc likcly than mcn to havc ccrtain typcs of thyroid
problcms, it was thought that a highcr incidcncc of thyroid discasc among
womcn might cxplain thc dihcrcncc. 5ut whcn womcn with rapid- cycling
bipolar disordcr wcrc tcstcd fr thyroid problcms, no grcatcr incidcncc of
thyroid discasc was fund. Thcorics implicating fcmalc hormoncs havc also
bccn suggcstcd, but so fr thcy arc mostly spcculativc, no rcscarch data cxist
clcarly proving that hormonal dihcrcnccs bctwccn mcn and womcn cxplain
this dihcrcncc.
Anothcr intriguing idca about thc incrcascd incidcncc of rapid- cycling
bipolar disordcr in womcn is rclatcd to thc hnding that womcn with bipolar
disordcr havc a slightly grcatcr ratio of dcprcssivc to manic cpisodcs than
mcn havc. Scvcral studics havc fund that womcn with bipolar disordcr
tcnd to havc morc cpisodcs of dcprcssion during thc coursc of thcir illncss
than mcn havc. ' This bcing thc casc, it may bc that womcn with bipolar dis-
ordcr arc morc likcly to bc trcatcd with antidcprcssants that can causc thcm
to cntcr a rapid- cycling phasc of thc disordcr. Thc typcs of clinical studics
that could provc this thcory havc yct to bc carricd out.
Thc hnding that womcn with bipolar disordcr havc morc dcprcssivc
cpisodcs than thcir malc countcrparts sccms to ht with thc hnding that
womcn arc morc likcly than mcn to suhcr hom nonbipolar dcprcssion. o
onc undcrstands this grcatcr tcndcncy of womcn to suhcr hom dcprcssivc
illncsscs. Rcscarch on thc lcvcls of thc fcmalc rcproductivc hormoncs in dc-
prcsscd womcn has gcncrally bccn unrcvcaling.
It is now known that thcrc arc many dihcrcnccs in brain organization
bctwccn womcn and mcn, dihcrcnccs that havc littlc to do with scx and rc-
production. Psychological tcsting prohlcs indicatc that womcn arc supcrior
to mcn in thcir pcrfrmancc on ccrtain tcsts of languagc and mcmory, mcn
pcrfrm bcttcr on ccrtain spccializcd tcsts of thrcc- dimcnsional visualiza-
tion. It is thought that thcrc arc subtlc dihcrcnccs in thc way thc brains of
mcn and womcn arc "wircd during prcnatal dcvclopmcnt, probably undcr
thc influcncc of hormoncs in thc womb, cspccially tcstostcronc. Thc dif-
fcrcnccs bctwccn mcn and womcn in thc incidcncc and symptom prohlc
of mood disordcrs may bc duc to thcsc dihcrcnccs in "wiring' Lxplaining
thc signihcantly highcr incidcncc of scrious dcprcssion, including bipolar
dcprcssion, in womcn is pcrhaps thc most important unanswcrcd gucstion
bcfrc us in thc hcld of womcn`s mcntal hcalth.
Postpartum Mood sordcrs and IamIy PIannng
Many clinical studics indicatc that womcn with bipolar disordcr arc at
vcry high risk fr an cpisodc of illncss in thc pcriod ahcr giving birth. nc
rcvicw articlc on bipolar disordcr in womcn put it this way. "Thcrc is no
othcr timc in thc lifc of any bipolar paticnt whcn thc risk of an cpisodc is
highcr than it is fr a fcmalc bipolar paticnt in thc post-partum pcriod''
Thc numbcrs arc indccd sobcring. studics havc shown that bctwccn 2 pcr-
ccnt and jO pcrccnt of womcn with bipolar disordcr who bccomc prcgnant
and dclivcr will havc an cpisodc of dcprcssion or mania cithcr during prcg-
1,0 P NV11LiS, L\SS, i1 LLiiL1LiS
nancy or fllowing dclivcry. 5ctwccn 8o pcrccnt and Ioo pcrccnt of womcn
with bipolar disordcr who stop taking mood- stabilizcr mcdication during
prcgnancy will cxpcricncc rclapsc soon ahcr discontinuing thc mcdication. '
Lpisodcs arc usually charactcrizcd by dcprcssivc or mixcd symptoms , purc
manic symptoms arc lcss common. Thus, many womcn who cxpcricncc a
"postpartum dcprcssion`' will turn out to havc bipolar disordcr, not "uni-
polar dcprcssion, and thc trcating physician nccds to carcmlly cvaluatc any
paticnt who dcvclops scrious dcprcssion fllowing childbirth fr this possi-
nc can spcculatc on why thc pcriod ahcr giving birth is such a high-
risk pcriod fr womcn with bipolar disordcr . thcrc arc thc cmotional and
physical strcss of labor and dclivcry, with thc incvitablc slccp dcprivation,
pcriods of physical pain, and thc dramatic changcs in thc lcvcls of rcproduc-
tivc and strcss hormoncs that attcnd childbirth. Although thc cxact rcasons
rcmain unknown, it appcars that thcsc sorts of cnvironmcntal issucs arc not
as important as biological fctors. youngcr agc and hrst prcgnancy arc two,
but thc most signihcant appcars to bc a fmily history of postpartum mood
disordcrs i n rclativcs. In onc study, having a rclativc who had suhcrcd a
postpartum cpisodc morc than doublcd thc risk fr postpartum rclapsc in
womcn with bipolar disordcr.`
Womcn with bipolar disordcr who want to havc a child arc thus fccd
with a challcnging dilcmma. n thc onc hand, physicians usually rccom-
mcnd that a woman not takc any mcdications during prcgnancy, to protcct
thc unborn child hom prcnatal cxposurc to pharmaccuticals. n thc othcr
hand, it is clcar that a woman with bipolar disordcr is at high risk fr rclapsc
ahcr giving birth and pcrhaps nccds mcdication latc in hcr prcgnancy morc
than at any othcr timc in hcr lifc. Anothcr problcm is that scvcral commonly
uscd mood-stabilizing mcdications havc bccn associatcd with birth dcfccts.
Thcrc arc no casy solutions to thcsc problcms, but a fcw fcts suggcst
somc ways out. Taking lithium during prcgnancy appcars to bc much safcr
than originally thought, although thcrc is an incrcascd risk of ccrtain vcry
scrious hcart malfrmations in thc child, thc absolutc risk is still guitc low-I
to 2 out of I, ooo. " Among thc anticonvulsants, valproatc and carbamazcpinc
havc dchnitcly bccn shown to causc birth dcfccts. Lamotriginc appcars to bc
much safcr, as do thc atypical antipsychotics.
nc fct, howcvcr, is vcry clcar . simply stopping all mcdications whilc
trying to gct prcgnant and fr thc duration of thc prcgnancy in ordcr to
climinatc all risk to thc fctus is vcry ris| fr thc mothcr. Somc womcn
will, of coursc, bc willing to takc this risk, and thcrc arc many argumcnts to
support this approach. 5ut thc hrst wccks and months-and somc say thc
hrst fcw momcnts-of mothcr- child contact arc vcry important fr mothcr-
child bonding, and this proccss may bc disruptcd if thc mothcr is dcprcsscd
LAi 1H 1PL1V 11SLV1V P 1,1
or hospitalizcd with bipolar symptoms. Anothcr vcry risky sccnario is thc
woman who unknowingly bccomcs prcgnant whilc taking mcdication fr
bipolar disordcr and thcn abruptly stops taking it. This is ris| fr thc child
bccausc by thc timc a woman discovcrs shc is prcgnant, thc fctus has al-
rcady bccn cxposcd to any mcdications shc is taking fr scvcral days to scv-
cral wccks. Signihcant organ dcvclopmcnt has alrcady occurrcd during this
timc. I'vc alrcady mcntioncd thc high risk of rclapsc in womcn who stop
mcdication trcatmcnt suddcnly during prcgnancy. Ior both of thcsc rca-
sons, I can`t strcss cnough that womcn with bipolar disordcr should plan
and prcparc fr prcgnancy so as not to bc fccd with such dimcult choiccs
and dccisions on short noticc.
Many womcn with bipolar disordcr havc hcalthy babics and rcmain wcll
in thc wccks and months fllowing dclivcry. Carcml planning, conscicntious
symptom monitoring, and timcly rcsumption of trcatmcnt will incrcasc thc
chanccs of this happcning. Thc woman with bipolar disordcr owcs it to hcr-
sclf and to hcr child to think and plan carcmlly about prcgnancy. Shc should
hnd an obstctrician and a psychiatrist who will support hcr dccision to bc-
comc prcgnant and work closcly with hcr and with cach othcr toward thc
hcalthicst possiblc outcomc fr both mothcr and baby.
Is it safc to brcast-fccd whilc taking mcdication Many mcdications arc
sccrctcd in brcast milk, including thosc uscd to trcat bipolar disordcr. Carc-
ml monitoring fr infnt cxposurc to pharmaccuticals by tcsting brcast milk
and thc baby's blood and urinc makc it possiblc fr somc paticnts to brcast-
fccd morc safcly whilc taking somc mcdications.
Prcmcnstrua Syndromcs
Thcrc has bccn intcnsc intcrcst fr many ycars in thc mood symptoms
that somc womcn cxpcricncc fr scvcral days bcfrc thc monthly onsct of
mcnstruation. Although many womcn cxpcricncc somc unplcasant physical
and psychological symptoms fr a fcw days bcfrc thcir pcriods, a subgroup
of womcn suhcr clinically signihcant and impairing mood symptoms prc-
mcnstrually and somctimcs midcyclc as wcll. Whcthcr womcn with bipolar
disordcr as a group arc morc likcly to havc cycling of thcir mood with thcir
mcnstrual cyclc is not clcar. Howcvcr, bipolar womcn who do cxpcricncc
this cycling can havc vcry signihcant and dcstabilizing mood fluctuations
that can makc thcir illncss morc dimcult to control. It has bccn shown that
womcn with such monthly mood cycling do not havc abnormal rcproductivc
hormonc lcvcls. Rathcr, it appcars to bc thc complctcly normal but dramatic
changcs of hormonal lcvcls during thc mcnstrual cyclc that arc rcsponsi-
blc fr thcsc mood fluctuations . nc way to addrcss thcsc symptoms is to
takc a contraccptivc. Such mcdications dampcn down thc normal cycling of
1,2 P NV11LiS, L\SS, i1 LLiiL1LiS
hormoncs and csscntially hold hormonc lcvcls to what is normally prcscnt
at thc bcginning of thc mcnstrual cyclc [whcn thc flow bcgins) . To prcvcnt
hormonal cycling, thc paticnt takcs activc mcdication all thc timc, skipping
thc placcbo [inactivc) pills that arc supplicd in most contraccptivc dispcns-
crs. This also mcans that thcrc is no monthly mcnstrual flow. Womcn who
noticc that mcnstrually rclatcd mood fluctuations consistcntly causc signih-
cant problcms fr thcm should considcr discussing this approach with thcir
psychiatrist and thcir gynccologist.
I can`t lcavc thc subj cct of prcmcnstrual mood symptoms without mcn-
tioning an intriguing study publishcd in thc Amcr|can)curna|c}Psycb|a|ry
by scvcral rcscarchcrs who had noticcd a signihcant ovcrlap bctwccn prc-
mcnstrual syndromc [PMS) symptoms and thc symptoms of scasonal ahcc-
tivc disordcr [SAO) . In both syndromcs dcprcsscd mood is accompanicd by
low cncrgy, a tcndcncy to slccp too much rathcr than too littlc, and an in-
crcasc in appctitc with carbohydratc craving. [Wc'll go into thc dctails of thc
symptoms of SAO in chaptcr i. ) Whcn thc rcscarchcrs askcd paticnts rc-
fcrrcd to a PMS clinic if thcir PMS was worsc during thc wintcr, about two-
thirds said that it was. f thc original group, 8pcrccnt mct thc diagnostic
critcria fr mll-blown scasonal ahcctivc disordcr. Thcsc womcn, thcn, had a
mood disordcr that cyclcd in at lcast |wcways . with thc monthly mcnstrual
cyclc and with thc twclvc-month cyclc of thc scasons. This study shows
us oncc morc that thcrc arc intricatc and complcx rclationships bctwccn
mood and bodily rhythms and cyclcs and that mood disordcrs arc ahcctcd
by many dihcrcnt fctors in ways wc arc only bcginning to undcrstand.
LAi 1H 1PL1V 11SLV1V P 1,j
L M A 1 H 4
hcrc is onc of thc most signihcant and most disturbing. according to onc
vcry important study, morc than opcrccnt of pcrsons with bipolar disordcr
also suhcr hom alcoholism or drug- abusc problcms. '
Oocs having bipolar disordcr makc individuals morc likcly to usc and
abusc drugs and alcohol Can alcoholism or drug abusc triggcr thc dcvcl-
opmcnt of bipolar disordcr in somconc who is gcnctically vulncrablc Oo
bipolar disordcr and substancc-abusc disordcrs havc a common biochcmi-
cal or gcnctic causc Thcrc is cvidcncc to support an answcr of ycs to all of
thcsc gucstions.
BpoIar Bngcs
Pcrhaps thc casicst- to- undcrstand modcl fr thc obscrvcd link bctwccn
bipolar disordcr and alcoholism and drug abusc is thc idca that thc mood
changcs of bipolar disordcr propcl pcoplc into situations thcy would othcr-
wisc bc ablc to avoid and causc thcm to do things thcy othcrwisc wouldn't do .

5rad was a frty-two-ycar-old writcr. Hc had a day j ob as a copywritcr
fr a small advcrtising hrm, but his crcativc juiccs rcally startcd flow-
ing latc at night whcn hc workcd on his "storics' In collcgc 5rad had
won a writing contcst and had sccn his vcry hrst attcmpt at writing a
short story publishcd in a prcstigious national publication. Sincc thcn
hc had publishcd onc or two storics a ycar, somctimcs in littlc litcrary
j ournals that paid him practically nothing, oncc in A||an||cMcn|b|y,
most ohcn in somcthing in bctwccn.
I hrst mct 5rad whcn hc was starting to gct trcatmcnt fr alcohol-
ism at thc substancc- abusc trcatmcnt fcility amliatcd with thc hos-
pital whcrc I workcd. A psychiatric consultation had bccn rcgucstcd
bccausc 5rad had told thc stah hc had bccn troublcd by dcprcssion and
thought it madc his drinking problcms worsc.
"I know what you'rc thinking. anothcr alcoholic writcr. 5ut
I'm not'
"Slow down, 5rad,' I said. "I didn`t cvcn know you wcrc a writcr
until you told mc just now' Hc was a scrious and intcnsc man with
dark, dccp- sct cycs. I had to admit hc lookcd thc part of thc troublcd
writcr. "5ut I'm intcrcstcd in hcaring your idcas about your drinking
"Sorry, I shouldn't jump to conclusions. 5ut pcoplc always think
of writcrs as alcoholics . You know, Hcmingway, Tcnncsscc Williams,
sitting at thcir typcwritcrs with a glass of Scotch. Wcll, I don't drink
whcn I writc, I drink whcn I can`t writc'
This was bcginning to sound intcrcsting. "What do you mcan I
5rad drank whcn hc couldn`t writc bccausc it madc him fccl bcttcr.
And it gradually bccamc clcar to mc that whcn hc couldn`t writc, it was
bccausc hc was dcprcsscd. "My mind just gocs blank fr days at a timc.
I gct bchind at work, I slccp too much, and I don`t cvcn bothcr turn-
ing thc computcr on at homc. I can gct thc car-wax and potato- chip
commcrcials writtcn at work, but I couldn't bc rcally crcativc if my lifc
dcpcndcd on it. This `what's thc usc' fccling comcs ovcr mc, and I hnd
mysclf bringing homc a hhh of vodka two or thrcc timcs a wcck and
just sipping thc nights away'
"Havc you cvcr uscd any othcr drugs Marijuana Cocainc I
"h, ycs,' 5rad said with a dccp sigh. "About thrcc ycars ago I
draincd my bank account ovcr a summcr-blcw it all on cocainc. If I
hadn't cndcd up in thc hospital, I might ncvcr havc stoppcd'
"What happcncd
"Wcll, this is rcally cmbarrassing. I don`t know what got into mc,
but I got this inspiration to try writing fr TV. I had ncvcr tricd script-
writing bcfrc, but I was surc I could do it. I got an idca fr a script
1LLHL11SA i11V\L \S P 1,j
about a guy who flls in lovc with a woman with a cocainc problcm.
I thought I nccdcd to do somc rcscarch-you know, whcrc you go to
buy thc stuh, what thosc arcas of town arc likc, thc pcoplc involvcd'
"Maybc you should havc tricd thc library hrst'
5rad turncd, looking at mc intcntly. At hrst I thought I had
ohcndcd him with my littlc attcmpt at humor. 5ut I hadn`t. " That's just
it,' hc said. " That's what I usually wcu|dhavc donc' Hc lookcd away
again. `+m not a particularly bravc pcrson, and ccrtainly not a fol.
5ut I was . . . I don`t know guitc how to put it . . . uninhibitcd, conh-
dcnt. I fund mysclf walking down strccts at midnight that I would
havc bccn ncrvous walking down in broad daylight. I bought thc stuh
and had no gualms about using it. And I was hookcd in no timc at
all. I would gct oh work, go homc, and writc until it got dark. Thcn
I'd makc a run fr thc cocainc, kind of cruisc around fr a whilc, thcn
comc homc and snort it. I'd gct back to thc writing and go at it until
thc sun camc up'
"Whcn did you slccp I askcd.
"I didn't, not fr days at a timc. I didn't nccd to. I fclt cncrgizcd all
thc timc'
"All thc timc
"Ycs, I think cocainc must ahcct mc dihcrcntly than it docs most
pcoplc. I was fccling high cvcn hours and hours ahcr I had uscd. ncc
thc high lastcd thrcc days'
This was sounding likc morc than just a drug and alcohol problcm.
Pcoplc don`t fccl high hom cocainc fr thrcc days. Somcthing clsc had
cncrgizcd 5rad that summcr. His mood and bchavioral changcs had all
thc hallmarks of hypomania.
"So how did you cnd up in thc hospital
"nc morning my hcart startcd bcating rcal fst and my chcst
startcd to hurt. I lch thc omcc and got mysclf to thc cmcrgcncy room.
Thcy wantcd to admit mc right away, but I wouldn't lct thcm'
"Why not
"It didn`t sccm ncccssary to mc. I thought my hcart was hnc, I just
wantcd somcthing fr thc pain. I know that sounds crazy now, but I
think I wasa littlc crazy by thcn. I don`t rcmcmbcr much about what
happcncd ncxt, but thcy told mc I startcd shouting and hghting. All
I know is I got two shots in thc butt and didn't wakc up until clcvcn
hours latcr'
Iortunatcly 5rad's hcart washnc, but hc was dischargcd with a
prcscription fr Rispcrdal to takc fr a fcw days fr what was callcd a
"cocainc-induccd psychosis' His slccp pattcrns and cncrgy lcvcl got
back to normal.
1, P NV11LiS, L\SS, i1 LLiiL1LiS
"It's mnny,' hc addcd, "I havcn`t had cvcn thc slightcst tcmptation
to usc cocainc again. I didn`t drink cithcr fr thc wholc ncxt ycar. 5ut
thcn I fund mysclf slipping into thc pit again, and I didn't havc thc
cncrgy to say no anymorc. 5ut this timc I kncw I nccdcd hclp. I think
mcmorics of that cocainc summcr madc mc rcalizc that thc drinking
might lcad to somcthing clsc again if I didn`t gct somc scrious trcat-
mcnt. That's why I chcckcd in hcrc'
I couldn't hclp asking onc morc gucstion bcfrc tclling 5rad I
thought hc probably had bipolar disordcr. "Oid you hnish thc script
"Ycs, I did. It turncd out grcat. I'vc scnt it to a produccr, and shc's
intcrcstcd. You know, I might cvcn makc back thc moncy I spcnt on
my, uh . . . rcscarch'

ot all storics likc 5rad's havc such a happy cnding. Somc pcrsons with
bipolar disordcr can indccd pull out of substancc abusc whcn thcir mood
cpisodcs comc to an cnd, cithcr spontancously or with trcatmcnt, but fr
othcrs thc substancc- abusc problcm takcs on a lifc of its own. In thc worst-
casc sccnario, thc mood disordcr and thc substancc-abusc disordcr start
fccding on cach othcr, and a vicious cyclc of mood symptoms, incrcascd
substancc abusc, and cvcn morc scvcrc mood fluctuations takcs ovcr until
it's impossiblc to scparatc onc problcm hom thc othcr.
Psychiatrists uscd to talk a grcat dcal about "sclf-mcdication in discuss-
ing thc rclationship bctwccn bipolar disordcr and substancc abusc. Thc idca
was that bipolar paticnts somctimcs startcd down thc road to a mll-blown
substancc-abusc problcm by attcmpting to "trcat thcir mood symptoms with
alcohol or drugs of abusc. Although this ccrtainly occurs in somc paticnts, it
docsn't sccm to bc thc most common sccnario. Although somc paticnts, likc
5rad, hnd thcmsclvcs drinking whilc dcprcsscd bccausc it dcadcns thc psy-
chic pain of dcprcssion, bipolar paticnts sccm at grcatcr risk fr alcohol and
drug abusc whcn thcy arc hypomanic or manic. 5rad's cocainc bingc is actu-
ally thc morc typical story. Thc "sclf-mcdication hypothcsis might prcdict
that bipolar paticnts would usc stimulants likc cocainc to allcviatc thcir dc-
prcssions. 5ut studics show that, likc 5rad, bipolar paticnts arc morc likcly
to usc cocainc-and to a lcsscr cxtcnt alcohol-to intcnsify and prolong
thcir hypomanic and manic statcs. '
Thc link bctwccn mania and cocainc abusc has convinccd many rc-
scarchcrs that it is manic disinhibition and loss of judgmcnt rathcr than a
tcndcncy to "sclf-mcdicatc that puts bipolar paticnts at such high risk fr
substancc abusc.
1LLHL11SA i11V\L \S M 1,,
EHcct, Causc, or Assocaton?
Anothcr possiblc rclationship bctwccn bipolar disordcr and substancc
abusc works in thc othcr dircction-that is, alcohol and drug abusc may
bring on cpisodcs of abnormal mood in bipolar- disordcr paticnts, pcrhaps
by triggcring cpisodcs in pcrsons who arc vulncrablc to thc disordcr bccausc
of gcnctic fctors. Scvcral studics havc shown that bipolar paticnts who havc
a substancc-abusc disordcr havc a stormicr coursc to thcir mood disordcr
than paticnts who do not abusc alcohol or drugs. "Oual- diagnosis paticnts,
on avcragc, hrst dcvclop symptoms of thcir bipolar disordcr at a youngcr
agc, and in somc studics thcy havc bccn shown to havc morc hcgucnt hos-
pitalizations . This has bccn intcrprctcd to indicatc that substancc abusc may
worscn thc coursc of bipolar disordcr, pcrhaps bccausc of somc dircct chcct
on thc brain causcd by rcpcatcd usc of drugs and alcohol. `
Iinally, it may bc that, likc bipolar disordcr, a vulncrability to addiction
has a strong gcnctic componcnt, and thc two problcms tcnd to occur to-
gcthcr simply bccausc thc gcncs fr both arc locatcd closc to onc anothcr on
thc chromosomcs and tcnd to bc inhcritcd togcthcr. I, fr onc, havc sccn too
many paticnts likc 5rad-paticnts whosc bipolar- disordcr symptoms and
substancc abusc sccm to triggcr and rcinfrcc cach othcr-to bclicvc that
thcsc so ohcn tightly intcrtwincd problcms arc randomly associatcd.
!sc or Ahusc?
At what point docs substancc usc bccomc "abusc [tablc Iy- I ) It would
bc casy fr mc to launch into a long and complcx discussion of diagnos-
tic critcria fr substancc abusc and chcmical dcpcndcncy, but that probably
wouldn`t bc vcry hclpml. I think thc issuc is guitc clcar fr individuals with
a mood disordcr. with thc possiblc cxccption of occasional alcohol usc, I
advisc pcrsons with a mood disordcr to scruu|cus|yavc|danyanda|||n|cx-
All abuscd substanccs appcar to work by stimulating "rcward ccntcrs in
thc brain. You havc probably hcard that laboratory animals will push a lcvcr
that dclivcrs an clcctrical stimulus to ccrtain brain rcgions rathcr than an-
othcr onc that dclivcrs fod to thcir cagc, and that thcy will continuc doing
so until thcy'rc practically dcad hom hungcr. Whcn a similar lcvcr dcvicc
is uscd to dclivcr an intravcnous dosc of alcohol or anothcr drug to labora-
tory animals, thc substanccs that animals will willingly and pcrsistcntly sclf-
administcr in this way arc almost cxactly thc samc oncs that humans usc to
gct intoxicatcd. narcotics, cocainc, and ccrtain stimulants and tranguilizcrs.
Thcsc arc thc samc substanccs that humans abusc and bccomc addictcd to.
Somc drugs, likc cocainc, ahcct thcsc ccntcrs guickly and powcrmlly, oth-
1, P NV11LiS, L\SS, i1 LLiiL1LiS
TzeirI-I Signs of alcoholism
Many medical and professional organizations endorse the CAGE questionnaire to
identi( problem drinking.
1. Have you ever felt you should Cut down on your drinkingr
z. Have people Annoyed you by criticizing your drinkingr
. Have you ever felt bad or Guilty about your drinkingr
. Have you ever had a drink nrst thing in the morning to steady your nerves or get
rid of a hangover an Eye opener)r
One ycs suggests a possible alcohol problem. More than one ycs means that an
alcohol problem is highly likely
Scurce atonal !nsttutc on AIcohoI Abusc and AIcoholsm, A|cchc||sm Ce|||ny |he Fac|s,
crs, likc marijuana, work morc slowly, but thcy all work thc samc way. by
disrupting thc normal opcration of thc brain`s "fccl- good circuitry.
ow, you don`t nccd to bc a psychiatrist to rcalizc that pcrsons with
bipolar disordcr alrcady havc cnough problcms with thc "fccl- good circuits
of thc brain, and that mucking things up mrthcr with "rccrcational drugs
is a vcrybad idca. Tcrc is somc cvidcncc to suggcst that intoxicating sub-
stanccs activcly intcrfcrc with thc thcrapcutic chccts of thc mcdications uscd
to trcat mood disordcrs. It sccms to mc that any usc of intoxicating sub-
stanccs by pcrsons with bipolar disordcr is unhcalthy and cxtrcmcly ris|
and fr thosc rcasons amounts to substancc abusc.
Tc gucstion that usually comcs ncxt is, Can`t I cvcn havc an occasional
glass of winc with dinncr Although I'm hard-prcsscd to frbid my paticnts
cvcr to drink, it's clcar that whcn it comcs to alcohol, lcss is bcttcr. Civcn thc
known high risk of bipolar paticnts fr scrious substancc- abusc problcms,
thc bcst coursc is probably no alcohol at all.
A cadIy Comhnaton
Tcrc is onc wcll- cstablishcd rcscarch hnding that is much morc signif-
icant than all thc spcculation about thc naturc of thc association bctwccn
bipolar disordcr and substancc abusc and cvcn morc disturbing than thc
cxtrcmcly high ratc of substancc abusc among pcoplc with bipolar disordcr.
Tis is thc hnding that pcrsons who havc mood disordcrs and also abusc
alcohol or drugs havc a grcatly incrcascd risk of suicidc. Scvcrc dcprcssion
complicatcd by alcoholism or drug abusc has bccn fund to bc onc of thc
most hcgucnt diagnostic picturcs in study ahcr study of thc psychiatric
diagnoscs of suicidc victims. In a Ij study attcmpting to makc psychi-
atric diagnoscs of suicidc victims, clinicians rcvicwcd thc mcdical rccords
1LLHL11SA i11V\L \S P 1,
and intcrvicwcd thc rclativcs of almost furtccn hundrcd pcrsons who had
committcd suicidc. This study, which fund that most of thc suicidc vic-
tims had suhcrcd hom a mood disordcr, also fund that ncar|yba{8pcr-
ccnt) had suhcrcd hom alcoholism or drug abusc. '
Anothcr point to cmphasizc hcrc is that whcn bipolar disordcr and a
substancc-abusc problcm cocxist, thcy |c|bnccd trcatmcnt. Cctting propcr
trcatmcnt fr thc mood disordcr will ccrtainly makc thc substancc- abusc
problcm casicr to trcat, but it cannot bc assumcd that a substancc- abusc prob-
lcm will simply go away whcn a cocxisting mood disordcr is trcatcd. An ac-
tivc substancc-abusc problcm will in fct makc thc mood disordcr dimcult
to diagnosc, lct alonc trcat.
Substancc abusc and addiction can bcst bc undcrstood as problcm |c-
bav|crs.A ccrtain bchavior bccomcs a problcm whcn thc individual cngagcs
in thc bchavior dcspitc ncgativc conscgucnccs that arc so signihcant that
continuing thc bchavior is litcrally sclf- dcstructivc. A pcrson who continucs
to drink alcohol or usc somc othcr intoxicating substancc dcspitc physical,
psychological, or social problcms that arc causcd or madc worsc by his usc
has a substancc-abusc problcm. Substancc abusc is not dchncd by physical
dcpcndcncc [somc substanccs, such as cocainc, don't cvcn causc physical dc-
pcndcncc) or by amount of usc. Loss of control and continucd usc dcspitc
ncgativc conscgucnccs dchnc substancc abusc.
Trcatng Suhstancc Ahusc and Addcton
Thc most important prcrcguisitc fr thc succcssml trcatmcnt of sub-
stancc abusc, or any problcm bchavior, i s acccpting thc nccd to stop thc disor-
dcrcd bchavior-that is, rccognizing that thc bchavior is causing problcms,
is out of control, and nccds to bc givcn up. This is ohcn thc most dimcult
stcp. Lnlcss thc pcrson ovcrcomcs dcnial ["I don`t havc a problcm, I can stop
any timc I want to) and acccpts his nccd to changc, trcatmcnt can`t cvcn gct
nc way to conccptualizc thc proccss of rccognizing this nccd to changc
bchavior is outlincd in thc |rans|bccrc||ca| mcdc|, morc commonly callcd
thc s|aycsc}cbanyc modcl, which was initially dcvclopcd spccihcally to dc-
hnc thc thought pattcrns and proccss of bchavioral changc in smoking ccs-
sation. ` It proposcs that individuals who succcssmlly changc an unhcalthy
bchavior pass through scvcral stagcs in thc proccss of changc, in a highly
prcdictablc way [hgurc Iy- I ) .
Thc hrst phasc i s callcd thc rcccn|cm|a||vcs|ayc. I n this phasc, indi-
viduals simply don`t considcr that thcy may havc a problcm. Thcy scc no rca-
sons fr stopping or gctting trcatmcnt, bccausc thcy havc littlc or no apprcci-
ation of thc ncgativc conscgucnccs and dangcr of thcir bchavior. Pcoplc with
10 M NV11LiS, L\SS, i1 LLiiL1LiS


50 00088
licuarI - I Stagcs of bchavioral changc. Pcoplc makc bchavoral changcs in
stagcs, moving clockwsc through thc cyclc hom rcccn|cm|a||vc[not acccpt-
ing thc nccd to changc) to ma|n|cnancc[maintaining thc bchavoral changc).
Many slip backard [countcrclockwsc in thc cyclc) on thcir way to rccovcry,
and many sudcr a hll rclapsc, movng hom maintcnancc to thc prccontcm-
plativc phasc and nccding to go through thc cyclc anothcr timc, cvcn multiplc
timcs, bcfrc achicving succcss.
problcm bchaviors cngagc in thcm bccausc doing so bcnchts thcm in somc
way. Orinking alcohol makcs you fccl good. It is an cxpcctcd part of many
social situations. It dccrcascs anxicty and boosts onc's mood a bit, at lcast
initially. In largc amounts, it dcadcns thc psychic pain of dcprcssion to somc
cxtcnt, at lcast fr a fcw hours [although wc know that alcohol and othcr in-
toxicating substanccs worscn dcprcssion whcn uscd rcgularly) . Ouring this
stagc, thc individual is continuing thc bchavior bccausc shc judgcs that thc
bcnchts of thc bchavior arc not outwcighcd by ncgativc conscgucnccs.
1LLHL11SA i11V\L \S M 11
It's important to cmphasizc hcrc that whcthcr c|bcrsthink that ncgativcs
outwcigh positivcs is not important. nly thc ahcctcd individual's judgmcnt
in this mattcr can lcad him to changc.
Thc ncxt phasc is known as thc ccn|cm|a||vcs|ayc. At this point in-
dividuals bcgin to scc that thcir bchavior has at lcast somc ncgativc consc-
gucnccs-to thcmsclvcs and thcir hcalth, or to thcir lovcd oncs. Thcy arc
bcginning to think thcrc might bc somc advantagcs to stopping thc bchavior
and may cvcn takc somc stcps to at lcast invcstigatc what that might cntail.
Thcy havc madc no commitmcnt to stop, but thcy arc at lcast somcwhat
opcn to thc possibility of stopping. This is onc of thc most important phascs
in thc cyclc, bccausc it is an important placc to intcrvcnc. Pcoplc can bc
stuck hcrc fr somc timc. thcy may fcar thc dimculty of stopping, fccl unccr-
tain about putting togcthcr a plan, or just bc "waiting fr thc right timc' This
is somctimcs as fr as a pcrson gcts in thc proccss of changc, and it can bc a
torturous timc in hcr lifc, shc now sccs thc ncgativc rcsults of hcr actions but
is still powcrlcss to stop.
Thc third phasc is known as thc ac||cns|ayc. Individuals takc stcps to
implcmcnt a plan to stop thcir ncgativc bchavior. This is also a crucial stagc
in thc proccss-if thc individual can`t tolcratc thc loss of thc bchavior's pos-
itivc chccts, hc may guickly givc up on this plan and movc back to thc con-
tcmplation phasc. Ouring thc action stagc, individuals nccd support, cmpa-
thy, and strong cncouragcmcnt to kccp on track and continuc in trcatmcnt.
If thc action individuals takc lcads to ccssation of thc bchavior, thcy
cntcr thc ma|n|cnanccs|ayc, in which thcy continuc to abstain hom ncga-
tivc bchaviors and havc coping mcchanisms and support in placc to do so.
As with thc action phasc, individuals may nccd a grcat dcal of support to
rcmain committcd to abstincncc. This can bc particularly important as thcir
situation improvcs and thc prcvious ncgativc conscgucnccs of thc bchavior
rcccdc. It is casy to scc how scductivc thoughts likc "j ust onc morc timc or
"I can handlc it now can sncak in.
nc important and uniguc aspcct of thc stagcs-of- changc modcl is that
it incorporatcs thc conccpt of rclapsc and sccs it as a common ncxt phasc
that many individuals movc into. Thc rc|ascs|aycis sccn not as a filurc but
simply as thc ncxt phasc in thc cyclc. Many pcoplc, whcn initially trying to
stop ncgativc bchaviors, will havc onc [or many) rclapscs. Sccing a rclapsc
as filurc cncouragcs thc pcrson to givc up, scc thc proccss as too hard, and
go back to hcr old ways. Thc stagcs-of- changc modcl sccs it as a ncarly in-
cvitablc conscgucncc of having a bchavioral disordcr and undcrstands that
pcoplc arc hcgucntly scduccd to rcvcrt back to thcir old ways whcn thcy
bccomc strcsscd, or, convcrscly, whcn thcy arc guitc happy and "lct thcir
guard down'
Many pcoplc cyclc through thc stagcs scvcral timcs bcfrc thcy havc
12 M NV11LiS, L\SS, i1 LLiiL1LiS
distanccd thcmsclvcs cnough hom thc problcm bchavior-fr which thcy
havc substitutcd hcalthy coping mcchanisms and now havc broad and dccp
support systcms-that cvcn maintcnancc is no longcr ncccssary, and thcy
cxit thc cyclc.
Psychiatrists and othcr mcntal-hcalth profcssionals arc wcll vcrscd in
thc availablc trcatmcnt rcsourccs in thcir community fr chcmical- dcpcn-
dcncy problcms. 5ut pcrhaps morc than most othcr typcs of mcntal-hcalth
problcms, thc trcatmcnt of alcohol- and drug- abusc problcms rcguircs a
widc rangc of spccializcd scrviccs and support groups. Mcntal-hcalth pro-
fcssionals will usually rcfcr a paticnt to a chcmical- dcpcndcncy ccntcr or
organization fr cvaluation and trcatmcnt of a chcmical dcpcndcncy. Trcat-
mcnt options might includc inpaticnt rchabilitation, outpaticnt trcatmcnt,
or a ncw typc of trcatmcnt program whcrcin paticnts spcnd thc day at thc
program and rcturn homc at night. Thcrc arc cvcn cvcning programs that
allow pcoplc to rcturn to work during thc day.
Thc hrst stcp is admitting that thcrc might bc a problcm. This is ohcn
thc most dimcult stcp. Whcn in doubt, talking about thcsc conccrns with thc
psychiatrist or thcrapist is not just important, it can bc litcrally lifcsaving.
1LLHL11SA i1 1V\L \S M 1
L M A 1 H
is thc scicncc of bodily rhythms and biological clocks. carly cvcry organ-
ism on thc planct livcs in rhythm with thc astronomical cyclcs of thc carth,
thc sun, and thc moon. Thc activitics of animals and thc growth cyclcs of
plants harmonizc with thc daily rising and sctting of thc sun, thc monthly
cbb and flow of occan tidcs, and thc annual cyclc of thc changing scasons.
Ancicnt pcoplcs crcctcd immcnsc astronomical calculators and obscr-
vatorics to track thcsc cyclcs at placcs likc Stonchcngc in Lngland and thc
monumcnts at Carnac in Irancc, whcrc rows of morc than a thousand stoncs
strctch across thc countrysidc. At thcsc sacrcd placcs and othcrs, includ-
ing thc pyramids of thc Mayans and thc Incas, ancicnt astronomcrs dctcr-
mincd thc datcs and timcs of solsticcs, cguinoxcs, and cclipscs . In fcstivals
likc thc Roman Saturnalia, our frcbcars cclcbratcd thc lcngthcning of thc
daylight hours that hcralds thc arrival of spring and thc rcturn of thc sun.
ur modcrn midwintcr holidays, Christmas and Hanukkah, rccall thcsc
scntimcnts with traditions ccntcrcd around candlcs, lights, and grccncry.
ncc wc humans lcarncd how to prcdict cclipscs, wc wcrc no longcr
tcrrihcd by thcm. As wc lcarncd how to cxtcnd thc daylight hours with hrc
and gaslight and clcctricity, wc dcpcndcd lcss on thc cyclcs of thc sun to
structurc our activitics and fclt morc in control of timc. Wc lcarncd to warm
oursclvcs in wintcr and cool oursclvcs in summcr. Thc changcs of scasons
wcrc still lovcly to watch and intcrcsting in thc way thcy ahcctcd thc plants
and animals around us, but thcy didn`t rcally ahcct us vcry much anymorc-
or so wc thought.
5ut thc changcs of thc scasons ccrtainly dc ahcct othcr crcaturcs. wc
know about thc migration of birds, salmon, and whalcs, Arctic rabbits that
changc color in wintcr , thc astonishing changcs in plant lifc that occur hom
fll to wintcr to spring, and, of coursc, thosc hibcrnating bcars. 5ut humans
havc cvolvcd bcyond all that, havcn't wc ur cyclcs of activity, likc our
slccping at night and bcing awakc during thc day, arc just convcntions sct
by our culturc rathcr than cxprcssions of our biology. Wc humans havc scv-
crcd our conncctions with thc rhythms of thc cclcstial bodics. Havcn`t wc
That's what many of us thought-until I8z, whcn a papcr by rcscarch-
crs hom thc ational Institutc of Mcntal Hcalth appcarcd in thc Amcr|can
)curna| c}Psycb|a|ry.

This papcr, titlcd "5right Artihcial Light Trcatmcnt

of a Manic-Ocprcssivc Paticnt with a Scasonal Mood Cyclc,' dcscribcd a
paticnt with bipolar disordcr whosc symptoms occurrcd in a pattcrn rclatcd
to thc scasons. dcprcssion in wintcr and mood clcvation during thc summcr.
Scasonal pattcrns in bipolar disordcr had bccn dcscribcd prcviously by
astutc clinicians, including [as you might cxpcct) Lmil Kracpclin, who ob-
scrvcd, "Rcpcatcdly in thcsc cascs, I saw moodincss sct in in autumn and
pass ovcr in spring `whcn thc sap shoots in thc trccs, to cxcitcmcnt'' 5ut
thcrc had bccn littlc organizcd rcscarch into thc rclationship bctwccn mood
and thc scasons. Thcn i n thc latc I;os, a group of rcscarchcrs wcrc drawn
togcthcr at IMH by a mutual intcrcst in scasonal mood changcs, and thcy
startcd to look at thcsc rclationships. nc of thcm, orman Roscnthal, had
fr ycars noticcd his own scasonal shihs of mood in his nativc South Ahica,
and hc had sccn thcsc mood swings worscn whcn his psychiatric training
brought him to cw York-a city locatcd much frthcr hom thc cguator
than his nativc [ohanncsburg had bccn. In cw York thc summcr days arc
much longcr and thc wintcr days much shortcr than in South Ahica. Roscn-
thal rccallcd his hrst autumn in cw York this way.
Oaylight-saving timc was ovcr and thc clocks wcrc put back an hour.
I lch that hrst Monday ahcr thc timc changc and fund thc world in
darkncss. A cold wind blowing oh thc Hudson Rivcr hllcd mc with
frcboding. Wintcr camc. My cncrgy dcclincd, and I wondcrcd how
I could havc undcrtakcn so many tasks thc prcvious summcr. Had I
bccn crazy ow thcrc sccmcd to bc no altcrnativc but to hang in and
try to kccp cvcrything afloat . . . . Iinally, spring arrivcd. My cncrgy
lcvcl surgcd again, and I wondcrcd why I had worricd so ovcr my
workload. '
Somc mood- disordcr paticnts with scasonal mood changcs fund out
about thc IMH group and sought out Roscnthal and thc othcr scicntists
working on scasonal mood disordcrs. nc was a woman who cxpcricnccd
rcgular wintcr dcprcssions charactcrizcd by low mood and thc dcvclopmcnt
of an intcnsc craving fr swccts and starchcs. Shc had madc an important
obscrvation during thc two wintcrs bcfrc shc camc to IMH. during both
of thosc wintcrs, shc had takcn vacations in thc Virgin Islands. n both oc-
casions, travcling south toward thc cguator-to a latitudc whcrc thc wintcr
days wcrc signihcantly longcr-rcsultcd in a dramatic improvcmcnt in hcr
mood. Iurthcrmorc, thc improvcmcnt vanishcd abruptly whcn shc rcturncd
to hcr coldcr-and darkcr-homc up north. It was bccoming obvious to thc
IMH tcam that thc crucial fctor in scasonal mood changcs was | |yb|.
Thc word bc|ccr|cd rcfcrs to thc lcngth of daylight hours in thc
twcnty- fur-hour day. It has bccn known fr many ycars that photopcriod
has a profund chcct on many living things. If you'vc cvcr put a poinscttia
plant or Christmas cactus in a dark closct to coax it into bloom fr thc holi-
days, you'vc uscd photopcriod manipulation to influcncc thc plant's physiol-
ogy. Thc shortcncd photopcriod causcs thc plant to producc hormoncs that
causc its flowcr buds to bc sct.
nc mcmbcr of thc IMH tcam suggcstcd trying to trcat wintcr dc-
prcssions by artihcially lcngthcning thc photopcriod. Scvcral paticnts vol-
untccrcd to sit in hont of bright lights fr scvcral hours bcfrc dawn and
scvcral morc ahcr sunsct. Within thrcc days thc hrst paticnt bcgan to fccl
bcttcr. "Thc changc was dramatic and unmistakablc,' Roscnthal latcr wrotc. '
Photothcrapy had bccn born.
Crcadan Rymms
Wc nccd to pausc hcrc and rcvicw an important conccpt in chronobiol-
ogy, c|rcad|anrby|bms. Thc tcrm comcs hom thc Latin words "circa,' mcan-
ing "around,' and "dicm,' mcaning "day' It rcfcrs to rhythms in thc body that
havc an approximatcly twcnty-fur-hour cyclc, that is, thc day-night cyclc.
It turns out that many bodily mnctions fllow a circadian rhythm. 5ody
tcmpcraturc cyclcs daily, with thc lowcst body tcmpcraturc occurring about
q. OO a. m. and thc highcst around . OO p. m. 5lood prcssurc drops whilc wc
arc aslccp and jumps up about . OO a. m. in rcsponsc to a surgc in thc adrcnal
hormonc cortisol, which itsclf riscs and flls in a twcnty- fur-hour cyclc.
Thc hormonc mclatonin, which is sccrctcd by thc pincal gland, locatcd dccp
within thc brain, has a circadian cyclc and appcars to bc vcry important in
rcgulating slccp and wakcmlncss, as anyonc who has uscd mclatonin pills to
hclp him slccp knows.
Humans, likc most animals, havc an intcrnal biological clock. It has
1 M NV11LiS, L\SS, i1 LLiiL1LiS
bccn dcmonstratcd undcr cxpcrimcntal conditions that this clock has a nat-
ural cyclc of about twcnty-]vc hours, but it is rcsct cvcry morning by cnvi-
ronmcntal cucs, primarily light, to stay in synch with thc twcnty-fur-hour
cyclc of thc day. Anothcr fct about this intcrnal clock, fmiliar to world
travclcrs, is that this "rcsct can shih by only about onc or two hours pcr
day. Whcn wc rcsct our watchcs fr daylight saving timc or travcl to an ad-
jaccnt timc zonc, wc hardly noticc thc changc. 5ut whcn wc travcl across
scvcral timc zoncs, it takcs scvcral days fr our intcrnal clock to bccomc
synchonizcd to thc ncw timc. Ouring that timc, wc awakcn and gct slccpy
at thc wrong timcs fr our ncw timc zonc and gcncrally fccl out of sorts, thc
phcnomcnon known as jct lag. Lvcntually, our intcrnal clock adjusts, but
thc frthcr wc'vc travclcd, thc longcr it takcs. about onc day fr cach hour
of timc changc. So what happcns to pcoplc whosc intcrnal clocks arc out of
synch with thcir cnvironmcnt fr prolongcd pcriods of timc
Lnglish rcscarchcrs sct out to invcstigatc this gucstion in thc latc Ios.
Thcy askcd furtccn hcalthy young mcn and womcn to voluntccr fr a bi o-
logical- clock cxpcrimcnt. Two or thrcc at a timc, thc voluntccrs cntcrcd cx-
pcrimcntal living guartcrs whcrc, fr about a month, instcad of a twcnty-
fur-hour day, thcy livcd on a thirty- hour day. twcnty hours of wakcmlncss,
tcn hours of slccp. Lvcry scvcral hours whilc awakc thcy took a tcn-minutc
battcry of psychological tcsts and ratcd thcir mood.
Sincc thcsc individuals wcrc frccd to livc on a thirty- hour cyclc, thcir
intcrnal clocks could ncvcrcatch up with thcir slccp-wakc cyclc. Ior thcm,
this schcdulc was thc cguivalcnt of travcling through hvc timc zoncs cvcry
day. Ouring thc cxpcrimcnt, thc rcscarchcrs had thc voluntccrs takc thcir
tcmpcraturc cvcry fcw hours, and in this way thcy wcrc ablc to dctcrminc
what timc it was fr cach pcrson`s biological clock. Thcy fund that thc
voluntccrs' intcrnal clocks wcnt in and out of synchronization with thcir
artihcially prolongcd slccp-wakc cyclc and that thc morc out of synchro-
nization thc voluntccrs wcrc, thc worsc thcir mood bccamc. In fct, it was
thc |n|crac||cn of thc two cyclcs that sccmcd to makc thc most dihcrcncc
in thcir mood. Thcy fclt worst whcn thcir intcrnal tcmpcraturc clock was
tclling thcm it wasn`t timc to gct up yct and thcir cnvironmcntally cnfrccd
slccp-wakc cyclc was tclling thcm it was timc to start winding down hom
a long day. Thc rcscarchcrs proposcd that "tcmporal alignmcnt bctwccn thc
slccp-wakc cyclc and thc intcrnal] circadian rhythms ahccts sclf- asscss-
mcnt of mood in hcalthy subj ccts'` Put morc simply. whcn our slccp-wakc
cyclc and our intcrnal clock arc out of synchronization, it has a vcry ncya||vc
chcct on our mood.
ScasonaI AHcctvc sordcr
Scvcral thcorics fr SAO involving circadian rhythms havc bccn put
frward, but nonc ht thc cxpcrimcntal hndings vcry wcll. It was proposcd
that pcoplc with SAO might havc an abnormal dclay in circadian rhythms.
Larly- morning bright light would bc cxpcctcd to corrcct this problcm by
advancing thc cyclc. Lvcning photothcrapy would bc cxpcctcd to havc thc
oppositc chcct and makc things cvcn worsc. 5ut rcscarch clcarly shows that
morning and cvcning photothcrapy arc cgually hclpml fr SAO. It has also
bccn suggcstcd that SAO paticnts havc lazy circadian rhythms and cvcn that
thcy arc abnormally scnsitivc to light. 5ut tcsts of thcsc hypothcscs havc lcd
to morc conmsion than clarity, and no onc has comc up with a thcory that
tics SAO to a particular circadian rhythm disturbancc.
A rcscarch group hom Columbia Lnivcrsity attcmptcd to discovcr thc
fctors that prcdictcd who would havc a good rcsponsc to photopcriod ma-
nipulation. Thcy gavc a coursc of photothcrapy to IOj pcoplc who rcportcd
scasonal mood changcs. Somc of thcsc individuals mct diagnostic critcria
fr bipolar I, somc fr bipolar II, and somc had unipolar dcprcssions-that
is, thcy had ncvcr bccn manic or hypomanic.
Thc rcscarchcrs fund that it was not diagnosis [as bipolar I or II or
nonbipolar dcprcssion) but a particular a||crnof dcprcssivc symptoms that
prcdictcd a good rcsponsc to photothcrapy. Thc pcoplc hclpcd by photo-
thcrapy tcndcd to slccp morc rathcr than lcss whcn thcy wcrc dcprcsscd
[hypcrsomnia) and to complain of low cncrgy and ftiguc. Thcy noticcd in-
crcascd appctitc during dcprcssions, cspccially fr swccts and starchcs ["car-
bohydratc craving), and an accompanying wcight gain. Iinally, thcy had a
striking diurnal variation in mood [a consistcnt pattcrn of changc in mood
through thc day) , but i n a pattcrn that was thc oppositc of that usually sccn
in scvcrc dcprcssion. instcad of waking up carly in thc morning with thc
worst mood of thc day and thcn fccling bcttcr as thc day wcnt on, thcsc
pcoplc fclt bcttcr in thc carly part of thc day but had an ahcrnoon or cvcning
"slump,' a pattcrn callcd rcvcrscd|urna|var|a||cn. "
I'vc bccn talking about SAO as if it wcrc a diagnostic catcgory of its own,
but it's not. SAO can rcfcr to a bipolar I, bipolar II, or nonbipolar dcprcssivc
illncss that shows a scasonal pattcrn in its symptoms. 5ut a lot of what wc
know about mood disordcrs suggcsts that bipolar I, bipolar II, and nonbi-
polar dcprcssivc illncsscs arc vcry d crcn|illncsscs in coursc and causation.
What docs it mcan that cacb can havc a scasonal pattcrn Thc study I dc-
scribcd carlicr showcd that it was not diagnosis but rathcr symptom pattcrn
that prcdictcd who gcts bcttcr with light thcrapy. Oocs this mcan that our
wholc diagnostic classihcation systcm is callcd into gucstion
Oon`t throw out your DSMjust yct. Thc bipolar-nonbipolar and bipolar
1 M NV11LiS, L\SS, i1 LLiiL1LiS
I-bipolar II diagnostic divisions arc still vcry uscml in choosing trcatmcnts,
and so is thc "with scasonal pattcrn-without scasonal pattcrn dcsignation.
It may just bc a fcw morc ycars bcfrc wc hgurc out how all thc classihca-
tions ht togcthcr.
In thc mcantimc, paticnts with bipolar symptoms who noticc a scasonal
pattcrn should talk with thcir physician about photothcrapy, cspccially if
thcy havc thc typical SAO dcprcssivc symptom pattcrn. low cncrgy, hypcr-
somnia, carbohydratc craving, wcight gain, and rcvcrsc diurnal variation of
mood [ahcrnoon or cvcning "slump) .
Scvcral ycars of rcscarch havc fund that bright bluc- tingcd light i s thc
most chcctivc fr trcating SAO, and thcrc arc now rclativcly incxpcnsivc
lights with this wavclcngth spccihcally dcsigncd to trcat SAO. Thc usual rcc-
ommcndation is that thc paticnt usc thc light in thc morning and start with
an cxposurc of thirty minutcs daily. A rcccnt study suggcsts that rcading
whilc in hont of thc light is cspccially bcnchcial, bccausc thc light rcflcctcd
hom thc pagc incrcascs thc total light cxposurc. Thc thcrapcutic chcct of
light thcrapy is somctimcs cvidcnt within days, but as with antidcprcssants,
scvcral wccks of thcrapy may bc nccdcd to obtain good rcmission of symp-
toms. Sidc chccts arc minor. hcadachcs and cycstrain, fr cxamplc. Too
much light cxposurc can somctimcs prccipitatc mild hypomanic symptoms.
irritability, insomnia, fccling "hypcr' Iortunatcly, this problcm sccms to rc-
spond guickly to dccrcascd light cxposurc, and photothcrapy docsn`t sccm
to havc thc risks of mood dcstabilization that taking antidcprcssant mcdi-
cation docs . Light thcrapy can bc thought of as an adjunctivc thcrapy fr bi-
polar disordcr with scasonal variation, an add- on trcatmcnt that works with
mcdication and psychothcrapy to rcgulatc mood through a natural cyclc of
thc body. Thcrc's anothcr cyclc that's also cxtrcmcly important to pay attcn-
tion to. thc slccp-wakc cyclc.
Thc SIccp CycIc and BpoIar sordcr
Wc'rc not hnishcd with circadian rhythms yct. nc of our most promi-
ncnt circadian rhythms, thc slccp-wakc cyclc, turns out to bc vcry signihcant
in bipolar disordcr. Thc study with our Lnglish voluntccrs dcmonstratcd
how important thc slccp-wakc cyclc is in thc rcgulation of mood in pcr-
sons who do nc|havc mood disordcrs. So it should comc as no surprisc that
slccp-wakc cyclc manipulation has dramatic chccts on pcrsons with bipolar
disordcr. Clinical obscrvations conhrm this. slccp dcprivation can bc uscd
thcrapcutically to trcat thc symptoms of dcprcssion, and it can also causc a
switch into thc manic statc. To undcrstand thcsc obscrvations, wc nccd to
takc a closcr look at normal slccp.
Ior guitc a long timc, slccp wasn't of much intcrcst to cxpcrimcntal
L| g0l Sl
H8| 0 y
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' '

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Iiouer I6-I Normal slccp architccturc.

. -

. |
6 7
psychologists and psychiatrists. Tis may sccm odd, cspccially considcring
Ircud's and othcrs' intcnsc intcrcst in drcams. Possibly bccausc of a lack of
invcstigativc tools, intcrcst in drcams ncvcr cxtcndcd to intcrcst in thc pro-
ccss of drcaming, and so thc physiology of slccp was a ncglcctcd arca of
rcscarch fr many dccadcs.
Tc changc camc in Iy, whcn a group of rcscarchcrs uscd an clcctro-
cnccphalogram [LLC) machinc on slccping voluntccrs in a clinical labo-
ratory t o invcstigatc thc long-standing obscrvation that pcoplc movc thcir
cycs bcncath closcd lids during somc pcriods of slccp. Whcn thc rcscarchcrs
awakcncd thc subj ccts during what camc to bc callcd ra|d cyc mcvcmcn|
s|cc [RLM slccp) , o pcrccnt of thcm rcportcd that thcy had bccn drcam-
ing. Iurthcr studics rcvcalcd that slccp is a complcx proccss, with scvcral
dihcrcnt stagcs and rhythms of activity that togcthcr arc now callcd s|cc
As hgurc I6- I indicatcs, ahcr flling aslccp, a pcrson passcs through
lightcr and thcn progrcssivcly dccpcr stagcs of slccp. 5rain activity slows,
and thc hcartbcat and blood prcssurc drop to thc lowcst lcvcls of thc twcnty-
fur-hour day. Tc proccss is likc a submarinc dcsccnding into darkcr, guictcr,
dccpcr watcr. Tc vcry dccpcst stagc is callcd s|cw-wavcs|cc [SWS) , bc-
causc thc LLC shows slow synchronizcd rhythms in thc clcctrical activity
of thc brain. SWS is thought to bc thc physically rcstorativc part of slccp,
cxpcrimcntal subj ccts who arc awakcncd whcncvcr thcy cntcr SWS but arc
allowcd to cxpcricncc thc othcr stagcs complain of musclc achcs and othcr
symptoms of physical discomfrt.
10 M NV11LiS, L\SS, i1 LLiiL1LiS
About nincty minutcs ahcr a pcrson flls aslccp, thc slccp "submarinc
bcgins to risc again. Thc LLC indicatcs a brain- activity pattcrn not vcry dif-
fcrcnt hom that sccn in awakc individuals. Thc LLC clcctrodcs that track
cyc movcmcnts mcasurc intcnsc activity, and individuals awakcncd during
this stagc rcport drcaming. thc slccpcr has cntcrcd a pcriod of RLM slccp.
Ahcr hhccn to twcnty minutcs of RLM slccp, cyc movcmcnt ccascs, and
thc slccpcr drihs back down into thc dccpcr stagcs again and has anothcr
pcriod of SWS, which prcdominatcs during thc hrst part of thc night. As
thc night progrcsscs, thc slccpcr spcnds morc timc in RLM slccp and lcss in
SWS. Toward dawn, slccp bccomcs lightcr and RLM pcriods bccomc longcr,
until hnally thc pcrson wakcs up. It is thought that RLM slccp and body
tcmpcraturc arc both tightly linkcd to thc body's main circadian clock [ ohcn
callcd thc s|rcnycsc|||a|cr), bccausc thc lowcst point of thc body's tcmpcra-
turc cyclc coincidcs with thc most intcnsivc pcriod of RLM slccp.
Whcn wc look at LLC slccp studics donc on dcprcsscd pcrsons, thc
RLM cyclc sccms to havc shihcd. Ocprcsscd individuals go into RLM al-
most immcdiatcly ahcr flling aslccp, a phcnomcnon callcd dccrcascdRM
|a|cncy. Somc slow-wavc slccp still occurs in thc latcr part of thc night, but
thc ovcrall amount of SWS is rcduccd. Somc rcscarchcrs havc intcrprctcd
thcsc hndings as indicating that dcprcsscd individuals suhcr hom a basc
advanccof thc RLM cyclc and that thc rhythm of thc strong oscillator has
gottcn out of phasc with othcr bodily rhythms. Wc saw hom thc study on
thc Lnglish voluntccrs that whcn thc strong oscillator [as mcasurcd by thcir
tcmpcraturc cyclc) is out of synchronization with thc slccp-wakc cyclc, dips
in mood occur. In thc fcw paticnts with bipolar disordcr who havc bccn
studicd, striking shihs of thc RLM and tcmpcraturc cyclcs wcrc obscrvcd as
thc paticnts cyclcd in and out of dcprcssion and mania.
Thcsc hndings bring togcthcr a lot of what wc know about thc symp-
toms of dcprcssion and about circadian rhythms. Thc dccrcascd amounts of
SWS may cxplain thc ftiguc and bodily discomfrt typical of dcprcssion.
Thc shihing of thc usual pcriod of RLM hom thc carly-morning hours to
thc carly part of thc slccp cyclc may cxplain thc carly- morning awakcning
typically sccn in dcprcssion.
Thcsc hndings may also cxplain thc thcrapcutic chccts of slccp dcpriva-
tion on symptoms of dcprcssion. Paticnts with thc typical diurnal variation
of mood sccn in dcprcssion ohcn rcport that thcy havc thcir bcst mood of
thc day during thc latc cvcning, bcfrc thcy go to slccp, and fccl thcir worst
in thc morning ahcr thcy'vc slcpt. This and othcr obscrvations lcd somc rc-
scarchcrs in thc Iyos to cxpcrimcnt with slccp dcprivation as a thcrapcutic
tcchniguc fr thc trcatmcnt of dcprcssion. With thc introduction of anti-
dcprcssant mcdications, intcrcst in slccp dcprivation fdcd, but rcccntly it
has bccn growing again. This work shows that if paticnts arc totally dcprivcd
of slccp-kcpt up all night-about 6o pcrccnt of thcm rcport a somctimcs
dramatic improvcmcnt in thcir mood. Lnfrtunatcly, thc chcct is tcmpo-
rary, i n most paticnts thc bcnchts disappcar ahcr cvcn a bricf nap, making
this intcrcsting tcchniguc a not tcrribly uscml onc. 5ut cxpcrimcnts with
partial slccp dcprivation indicatc that waking paticnts up at about z. oo a. m.
and making surc that thcy do not slccp during thc sccond half of thc night
is ncarly as chcctivc as total slccp dcprivation. Advancing thc slccp cyclc by
six hours, so that paticnts go to slccp at 6. oo p.m. and gct up at z. oo a.m., has
also bccn fund to havc antidcprcssant chccts.
Although thc tcchniguc has not caught on in thc Lnitcd Statcs, slccp
dcprivation and phasc advancc arc popular in Luropc as adjuncts to mcd-
ication in thc trcatmcnt of bipolar and nonbipolar dcprcssion. An Italian
study publishcd in I comparcd thc rccovcry timc hom dcprcssion in tcn
bipolar paticnts. All of thcm wcrc trcatcd with fluoxctinc [Prozac) , but hvc
wcrc also givcn scvcral cyclcs of total slccp dcprivation. Thc paticnts who
had slccp dcprivation got bcttcr fstcr on thc mcdication than thosc who
did not. '
Thc othcr rclcvant clinical obscrvation about slccp in pcrsons with bi-
polar disordcr is that slccp dcprivation can prccipitatc mania. This is a vcry
wcll-documcntcd hnding, and fr this rcason my discussion of slccp dcpri-
vation as a trcatmcnt fr dcprcssion comcs with a "don`t try this at homc
warning. cvcn onc night of slccp dcprivation can prccipitatc mania. Thcrc
havc bccn numcrous rcports of individuals with bipolar disordcr bccoming
manic ahcr transatlantic flights or ahcr slccp dcprivation causcd by mcdical
cmcrgcncics or fmily criscs. Lmotional upscts can, of coursc, lcad to in-
somnia and poor slccp bccausc of anxicty. It has bccn proposcd that lack of
slccp fr anyrcason may bc what tips thc balancc fr many bipolar paticnts
and brings on an cpisodc of mania. '"
All of thc work on chronobiology and biological clocks indicatcs that
thcrc arc important links bctwccn bodily rhythms and mood, and wc'vc barcly
scratchcd thc surfcc of this fscinating arca of study. So far wc havc only
tantalizing hints about thcsc links rathcr than clcarly undcrstood mccha-
nisms and rclationships. cvcrthclcss, studics of slccp and SAO point thc
way toward ncw and safcr trcatmcnts fr ccrtain mood disordcrs-tcch-
nigucs likc photothcrapy and slccp phasc advancc. This work also indicatcs
thc importancc of lifcstylc rcgularity in controlling thc symptoms of bipolar
disordcr, a topic wc'll cxplorc in morc dctail in chaptcr zo.
12 M NV11LiS, L\SS, i1 LLiiL1LiS
L M A 1 H
O LODO11CS O1 1O1d1 I1SO1UO1
in clustcrs within fmilics. In Man|c-Dcrcss|vc Insan||y, Lmil Kracpclin
wrotc of onc fmily in which "of thc tcn childrcn of thc samc parcnts who
wcrc both probably manic- dcprcssivc by prcdisposition, no fcwcr than
scvcn fcll ill thc samc way, of thc hvc dcsccndants of thc sccond gcncration,
fur havc alrcady fllcn ill.' '
Ior many ycars rcscarch on thc gcnctics of bipolar disordcr was ham-
pcrcd by fggy diagnostic critcria and a lack of laboratory mcthods to
idcntify gcncs. 5ut this statc of ahairs has changcd dramatically. ot only
havc psychiatrists bccomc morc skillcd in thc diagnosis of bipolar disordcr,
but thc biochcmical mcthods availablc to locatc and idcnti gcncs on thc
human chromosomc havc bccomc trcmcndously morc sophisticatcd. Thcsc
dcvclopmcnts will, sooncr or latcr, lcad to a bcttcr undcrstanding of thc gc-
nctic mcchanisms of bipolar disordcr, which will in turn lcad to bcttcr diag-
nosis and trcatmcnt of thc disordcr.
Gcncs, Chromosomcs, and MA
Thc pattcrns and rulcs of inhcritancc in living things wcrc hrst dcscribcd
by Crcgor Mcndcl, an Austrian monk who ovcr many ycars pcrfrmcd clc-
gantly planncd and cxccutcd cxpcrimcnts with plants, mostly gardcn pcas,
in his monastcry gardcn. Mcndcl discovcrcd that traits arc transmittcd hom
parcnt to child in discrctc bits of infrmation, bits that wc now call ycncs,
thc units of inhcritancc.
Wc now undcrstand that gcncs arc scts of instructions fr building pro-
tcins. All plants and animals, hom scawccd to snapdragons and hom carth-
worms to clcphants, arc constructcd of and opcratc by mcans of protcins.
Myosin [musclc protcin), hcmoglobin [thc oxygcn-carrying protcin of rcd
blood cclls) , and collagcn [thc structural protcin of skin and cartilagc) arc
just a fcw cxamplcs. Lvcn thc nonprotcin structural matcrials of thc body,
such as thc calcium salts in our boncs, dcpcnd on protcins. Protcins callcd
cnzymcs dircct thc manufcturc of bonc hom calcium salts by cxpcditing
ccrtain chcmical rcactions. Many hormoncs arc protcins [insulin, fr cx-
amplc) , and thosc that arc not [fr cxamplc, tcstostcronc and cortisol) arc
manufcturcd by protcin cnzymcs. All protcins arc built according to spcci-
hcations containcd in gcncs.
Ior many ycars what gcncs wcrc madc of and cxactly how thcy wcrc
transmittcd hom parcnt to ohspring was a complctc mystcry. 5ut by thc
mid- I(os, cxpcrimcnts with bactcria had shown that a fmily of biochcm-
ical compounds fund in cclls, callcd nuc|c|cac|ds, containcd gcnctic infr-
mation. In Iy [amcs Watson and Irancis Crick publishcd a papcr in thc
5ritish scicntihc j ournal Na|urc, dcscribing thc structurc of thc most im-
portant of thcsc compounds, dcoxyribonuclcic acid [OA), and thc modcrn
agc of gcnctics had bcgun.
OA molcculcs arc long spiral chains whosc links consist of fur sim-
plcr compounds callcd nuclcotidcs. Thc fur OA nuclcotidcs, adcninc, cy-
tosinc, guaninc, and thyminc [usually abbrcviatcd as A, C, C, and T) , arc thc
clcmcnts of an clcgantly simplc codc. [ust as you can writc out a Morsc codc
vcrsion of Ham|c|using only dots and dashcs, you can writc out instructions
fr building hcmoglobin, myosin, collagcn, or any othcr protcin using As,
C's, C's, and T's. That's what OA docs. You can think of thc physical struc-
turc of a gcnc as thc scction on thc OA molcculc that contains thc codc fr
onc protcin.
Whcn thc OA molcculc is doing its work in thc ccll, it is unravclcd and
strctchcd out, surroundcd by a wholc rctinuc of ultramicroscopic attcndants
busily rcading thc codcd instructions and making protcins. Whcn it's timc
fr thc ccll to dividc, anothcr sct of attcndants carcmlly coil thc OA mol-
cculc into a compact cylindcr and surround it with protcctivc protcins to
frm thc thrcadlikc structurcs you may havc lookcd at undcr thc micro-
scopc in high school biology. thc chromosomcs.
1q M NV11LiS, L\SS, i1 LLiiL1LiS
Gcnctc scascs
Ior somc disordcrs, thc links hom a ccrtain gcnc to a ccrtain protcin
to a ccrtain trait or discasc arc casy to fllow. Sicklc- ccll ancmia is onc such
discasc. Whcn thc blood of sicklc-ccll paticnts is cxamincd undcr thc micro-
scopc, instcad of sccing thc normal sauccr- or disk-shapcd rcd blood cclls,
onc sccs abnormal crcsccnt- or sicklc-shapcd cclls . ncc scicntists had thc
biochcmical mcthods that allowcd thcm to look at thc componcnts of blood
cclls, thcy discovcrcd that sicklc-ccll paticnts had an abnormally shapcd hc-
moglobin molcculc [hcmoglobin is thc protcin in rcd blood cclls that trans-
ports oxygcn) . This abnormal hcmoglobin tcnds to frm abnormal chains
within thc ccll, strctching thc normally disk-shapcd cclls into thc sicklc
shapc charactcristic of thc discasc.
5ccausc hcmoglobin is casily purihcd, it was onc of thc hrst protcins
whosc structurc was complctcly dcscribcd [a fcat that carncd Cambridgc
Lnivcrsity biochcmist Max Icrdinand Pcrutz thc obcl Prizc in I6z) . Rc-
scarchcrs discovcrcd that sicklc- ccll hcmoglobin [now callcd hcmoglobin
S) dihcrs hom normal hcmoglobin by only onc molccular clcmcnt that is
causcd by a singlc misprint in thc hcmoglobin gcnc of pcrsons with thc dis-
casc. At onc particular spot on thc OA molcculc of pcrsons with sicklc- ccll
ancmia, thcrc is an A instcad of a T. An abnormal hcmoglobin molcculc
rcsults hom thc rcading of thcsc incorrcct instructions, and thc abnormal
hcmoglobin molcculcs causc thc abnormally shapcd rcd blood cclls, which
block blood vcsscls and rcsult in thc symptoms of thc discasc. Thc pathway
hom abnormal gcnc to abnormal protcin to abnormal cclls to symptoms has
bccn complctcly dcscribcd.
Ccncs havc bccn idcntihcd and locatcd in scvcral othcr human discascs
whosc inhcritancc pattcrn indicatcs that thcy arc singlc-gcnc illncsscs, in-
cluding cystic hbrosis, many frms of hcmophilia, and Ouchcnnc's muscular
What Wc Know
In thc abscncc of spccihc idcntihcd gcncs or any knowlcdgc about what
protcins thcsc gcncs codc fr, wc can talk about thc inhcritancc of bipolar
disordcr in only a vcry gcncral way. Childrcn of individuals with bipolar
disordcr havc an incrcascd risk of dcvcloping bipolar disordcr. Assigning a
numbcr to that risk is vcry dimcult, fr somc of thc samc rcasons that thc
scarch fr a bipolar gcnc has bccn so dimcult, cspccially problcms of diag-
nosis. 5ut thc risk sccms to bc scvcral timcs that of thc gcncral population,
on thc ordcr of Io pcrccnt. Howcvcr, childrcn of pcrsons with bipolar disor-
dcr arc also at a highcr risk fr unipolar [dcprcssion-only) illncss, and whcn
H Li1LS L1 1PL1V 11SLV1V M 1j
you add in this risk, thc pcrccntagcs go up into thc high twcntics. This mcans
that thc childrcn of pcrsons with bipolar disordcr havc about a onc- in-
fur chancc of dcvcloping somc kind of mood disordcr and about a onc-
in- tcn chancc of dcvcloping bipolar disordcr.'
Individuals with bipolar disordcr nccd to bc alcrt to signs and symp-
toms of mood disordcrs in thcir childrcn and to gct thcm into trcatmcnt
if such symptoms occur. Although wc may bc unccrtain about thc dctails
of thc inhcritancc of bipolar disordcr, wc arc not at all unccrtain about thc
importancc of carly diagnosis and trcatmcnt.
Thc Scarch Contnucs
Scvcral fctors makc scicntists optimistic about cvcntually discovcring
gcncs fr bipolar disordcr. Thc cxplosivc growth of tcchnologics availablc
to gcncticists is pcrhaps thc primary rcason fr optimism. Thc Human Cc-
nomc Proj cct was ablc to tacklc thc scgucncing of thc OA in all (6 human
chromosomcs only ahcr automatcd tcchnology to pcrfrm OA scgucnc-
ing bccamc availablc in thc Ios and whcn supcrcomputcrs wcrc dcvclopcd
that could analyzc thc litcrally astronomical amount of data that was gcn-
cratcd. This tcchnology has advanccd cvcn mrthcr in thc intcrvcning ycars,
and it is now possiblc to tcst fr 1 m||||cn gcnctic markcrs in an individual
using a siliconc "chip callcd a "OA microarray that costs only a fcw hun-
drcd dollars to manufcturc. It will soon bc possiblc to scgucncc thc cntirc
gcnomc of an individual fr lcss than onc thousand dollars, a possibility all
thc morc amazing whcn onc lcarns that thc budgct of thc invcstigation that
rcsultcd in thc hrst wholc-gcnomc scgucncing was in thc tcns of millions of
Lvcn whcn gcncs arc idcntihcd, howcvcr, and tcsts arc dcvclopcd that
can look fr thcsc gcncs in individuals, prcdictions about who will dcvclop
symptoms will still bc imprccisc. This is bccausc scvcral gcncs arc likcly in-
volvcd and also bccausc gcnctics is almost ccrtainly not thc wholc story in
bipolar disordcr. Lnvironmcntal fctors arc undoubtcdly important [pcr-
haps cgually important) in dctcrmining who will and will not bc ahcctcd,
psychological and pcrhaps physical strcsscs and traumas arc probably vcry
important. So cvcn whcn a gcnc or gcncs arc idcntihcd and can bc tcstcd
fr, hnding that a pcrson has a bipolar gcnc will probably mcan that hc or
shc has a highcr chancc of dcvcloping symptoms than somconc who docs
not havc thc gcnc-but not a Ioo pcrccnt chancc. This will raisc a lot of
gucstions about who should and should not bc tcstcd and who is cntitlcd to
know gcnctic tcst rcsults.
5ut hnding rcsponsiblc gcncs may lcad to ncw trcatmcnt approachcs
that will bcncht cvcryonc with mood disordcrs. Ccnc idcntihcation, as wcll
1 M NV11LiS, L\SS, i1 LLiiL1LiS
as idcntihcation of thc mnction of thcsc gcncs or thc gcnc products, will
undoubtcdly shcd light on thc biochcmical basis of bipolar disordcr. It may
thcn bc possiblc to dcsign mcdications or othcr trcatmcnts bascd on knowl-
cdgc about thc causcs of bipolar symptoms on a ccllular or biochcmical
lcvcl-rathcr than stumbling upon trcatmcnts by accidcnt, as has bccn thc
casc so fr. Ccnctics rcscarch is onc of thc most challcnging but most prom-
ising arcas of invcstigation of bipolar disordcr, and it holds thc promisc of
truly rcvolutionizing thc trcatmcnt of this discasc.
H Li1LS L1 1PL1V 11SLV1V M 1,
1O1d1 1O1O@
L M A 1 H b
that tcll us a lot about bipolar disordcr. A common thcmc in thcm, it sccms,
is to show that staying wcll with bipolar disordcr dcpcnds guitc a lot on
taking carc of onc's gcncral hcalth. In part IV of thc book [chaptcrs zo-z) ,
I will discuss somc of thc lifcstylc changcs that arc vital i n hclping pcrsons
with bipolar disordcr stay wcll. Many of thcsc changcs arc such things as
gctting a good night's slccp, cxcrcising rcgularly, and cating a hcalthml dict.
ow I know somc rcadcrs [surcly not you) will rcad through that list and
say to thcmsclvcs, "Right, a good night's slccp, cxcrcising, blah, blah, blah. I
know all that stuh. Tcll mc somcthing |mcr|an|'`Wcll, this ncxt scction, on
strcss, cxplains cxactly why thcsc things arc important and why strcss is nc|
good fr your brain.
How thc Body HandIcs Strcss
Thc most dramatic bodily rcsponsc to strcss is thc fmiliar "hght or
flight rcsponsc. If you arc hiking along thc Appalachian Trail and suddcnly
cncountcr a bcar twicc your sizc, somc dramatic physical changcs takc placc
in thc body, changcs that prcparc you to fcc combat with thc crcaturc
["hght) or, pcrhaps morc likcly, run as fst and as far as you can ["flight).
Thcrc i s a hormonally triggcrcd flood of cncrgy- containing glucosc, ft mol-
cculcs, and protcins into your bloodstrcam, your hcart ratc and blood prcs-
surc go up, to gct thcsc cncrgy molcculcs to thc musclcs as guickly as possi-
blc, and your brcathing bccomcs fstcr and dccpcr to providc thc oxygcn
nccdcd to turn thc cncrgy molcculcs into powcr. Simultancously, body sys-
tcms that arc not involvcd in hghting or flccing shih down. digcstion slows
down, ccllular growth and tissuc rcpair grind to a halt, and cvcn thc immunc
systcm tcmporarily gocs into hibcrnation. Thc strcss rcsponsc is rcally a bril-
liantly orchcstratcd symphony of physiological rcsponscs in many organ
systcms that prcparcs thc body fr intcnsc physical cxcrtion. All of this is
tcrrihc in a physical cmcrgcncy, but if this hypcractivc physiology gocs on fr
too long, bad things bcgin to happcn.
In othcr animals, thc strcss rcsponsc is cithcr activc or inactivc, thc sys-
tcm is cithcr "on`' or "oh.' 5ut in humans [ and thc animals most closcly rc-
latcd to thcm) , clcmcnts of thc strcss rcsponsc can bc activc fr much longcr
pcriods of timc. curoscicntist Robcrt Sapols| highlightcd this dihcrcncc
bctwccn humans and othcr animals in a book about thc rolc of strcss in
hcalth and discasc that hc callcd WyZc|rasDcn`|Gc|C|ccrs.Thc titlc rcfcrs
to thc fct that whcn a grazing zcbra spots a lion on thc cdgc of thc junglc, its
strcss rcsponsc kicks in at mll frcc and thc animal bounds oh at brcakncck
spccd, but thcn, if it's bccn fst cnough and lucky cnough, thc zcbra cscapcs
thc hungry lion and simply rcsumcs cating, as calm and placid as if nothing
had happcncd, with bodily mnctions guickly rcturning to basclinc. thcr
than thc sight of a lion, thcrc isn`t much that brings on thc strcss rcsponsc in
zcbras, bccausc zcbras don't havc thc cognitivc capacity to worry. 5ut wc arc
guitc dihcrcnt. "Wc humans can bc strcsscd by things that simply makc no
scnsc to zcbras . . . . It is not a gcncral mammalian trait to bccomc anxious
about mortgagcs or thc Intcrnal Rcvcnuc Scrvicc, about public spcaking or
fcars of what you say in a job intcrvicw, about thc incvitability of dcath.''
cvcrthclcss, thcsc vcry un- zcbralikc sourccs of strcss activatc many of thc
samc physiological rcsponscs in thc human body as our zcbra`s sighting of
thc lion or our hikcr's cncountcr with thc bcar.
Thc main hormoncs rcsponsiblc fr thc strcss rcsponsc arc thc y|uccccr-
||cc|ds, a group of hormoncs that arc produccd by thc adrcnal glands, and
thc most important of thcsc is ccr||sc|. You can think of cortisol as rcspon-
siblc fr controlling thc changcs to thc cncrgy cconomy of thc body that
arc part of thc strcss rcsponsc. thc rclcasc of glucosc into thc bloodstrcam,
thc damping down of thc immunc systcm, and thc supprcssion of ccllular
growth. It is this last fcaturc of cortisol that is most rclcvant to pcrsons with
bipolar disordcr.
As you may rcmcmbcr hom chaptcr , our mood-rcgulation systcm
dcpcnds on thc constant activc rcmodcling of nctworks of ncurons in thc
brain, cspccially in an arca of thc brain callcd thc hippo campus. Thc cclls in
thc hippocampus arc vcry busy, sprouting ncw conncctions and disconncct-
ing and rcconnccting with othcr ncurons, and ncw ncurons arc constantly
1PL1V 1L1LLY M 1
Iiouer i8- i Thc cdccts of chronic strcss on hippocampal ncurons. / is a
rcprcscntativc ncuron hom a control animal, and Bis hom an animal that was
subj cctcd to chronic strcss fr scvcral hours daily fr tcn consccutivc days.
Scurce A. Vyas, K. Mtra, b. Kao, and S. Chattarj, "Chronc Strcss !nduccs Contrastng
Iattcrns oI Ocdrtc Kcmodclng n Ippocampal and AmygdaIod curons, ]curna| c)
Neurcsc|ence zz (zooz). 68to-t8.
nccdcd to rcplcnish thc oncs that simply wcar out hom all this work. It's casy
to scc, thcn, how too much cortisol damping down ccllular growh ovcr too
long a timc can havc a vcry dclctcrious chcct on thc mood systcm.
Tc damaging chcct of high lcvcls of cortisol on thc brain has bccn
abundantly dcmonstratcd in animal studics. Micc arc timid littlc crcaturcs.
Tcy scurry around thcir cnvironmcnt, not bcing still fr vcry long cxccpt
to cat, and thcy prcfcr darkncss. A rclativcly humanc way to subj cct micc
to strcss, thcn, is to conhnc thcm to a Lucitc tubc in a wcll- lit cnvironmcnt
fr scvcral hours. If you do this day ahcr day, an cxpcrimcntal tcchniguc
known as "chronic immobilization strcss,' thc micc will cxhibit changcs in
thcir bchavior that rcscmblc dcprcssion in humans. Tcy don`t cat as much
and thcy losc wcight. Slccp is disruptcd and scxual activity rcduccd. Tcy arc
lcss activc, thcy spcnd lcss timc running on thc whccls that havc bccn put
in thcir cagcs. Tcsts of objcct rccognition and mcmory show that thcir cog-
nitivc mnctioning suhcrs as wcll. Whcn thc blood lcvcl of corticostcronc,
thc mousc cguivalcnt of cortisol, is mcasurcd, it is fund to bc clcvatcd. 5ut
thc most striking hndings involvc changcs in ncurons in thc hippocampus.
As Iigurc i8-ishows, whcn thc hippocampal ncurons of micc subj cctcd to
chronic strcss arc comparcd to thosc of control micc, thc dihcrcncc is un-
200 M NV11LiS, L\SS, i1 LLiiL1LiS
Thc ncurons of thc strcsscd animals look shrunkcn and stuntcd, com-
parcd to thosc of thc nonstrcsscd animals. Most importantly, rcscarch has
shown that it is cortisol that is rcsponsiblc fr thcsc changcs. Inj ccting thc
rodcnt cguivalcnt of cortisol [ corticostcronc) into animals that arc not sub-
jcctcd to chronic strcss produccs cxactly thc samc chcct. shrunkcn brain
cclls in thc hippocampus, thc arca of thc brain thought to bc thc most im-
portant in mood rcgulation. '
5ut hcrc's thc most imprcssivc thing of all. strcss- causcd damagc to brain
cclls in thc hippocampus can bc rcvcn|cdby lithium. Scicntists at Rockc-
fcllcr Lnivcrsity, along with collcagucs in othcr institutions, dcsigncd an
cxpcrimcnt to invcstigatc whcthcr lithium might protcct ncurons in thc hip-
pocampus hom thc chccts of strcss. Somc cxpcrimcntal micc wcrc dividcd
into two groups. nc group was givcn lithium fr two wccks and thc othcr
was not, thcn both groups wcrc subj cctcd to chronic strcss. Iigurc I8-z is
onc of thosc picturcs worth a thousand words.
Thc hrst ccll is hom a control animal that was not subj cctcd to strcss, it
shows a normally dcvclopcd ccll [A) . Ccll is a rcprcscntativc ncuron hom
a strcsscd mousc, showing, as cxpcctcd, a stuntcd and shrunkcn ccll. Cis a
ccll hom thc hippocampus of a mousc that rcccivcd lithium fr two wccks
Iiouer I8-z Protccting hippocampal ncurons hom thc damaging cdccts of
chronic strcss wth lithium. / is a rcprcscntativc hippocampal ncuron hom a
control animal, is hom an animal subj cctcd to twcnq- onc days of immobi-
lization strcss, and Cis hom a strcsscd animal that had bccn prctrcatcd with
lithium fr two wccks bcfrc cxpcricncing thc strcss.
Scurce G. Wood, L. Young, L. Kcagan, b. Chcn, and b. McLwan, "Strcss-!nduccd Structural
KcmodcIng n thc Ippocampus: Ircvcnton by Lthum 1rcatmcnt, Prcceed|nys c) |he
Na||cna| Academ) c) Sc|ences tot (zoo|). ;-;8.
1PL1V1L1LLY M 201
bcfrc bcing subj cctcd to strcss and continucd on lithium through thc pc-
riod of strcss. You don`t nccd to bc a ncuroscicntist to scc that thc ccll hom
thc lithium- trcatcd mousc C)was protcctcd hom thc chccts of strcss and
looks just as hcalthy as thc onc hom thc control animal A) .
So what should wc concludc hom all this Iirst of all, strcss i s no| good
fr your brain. Strcss raiscs thc lcvcls of stcroid hormoncs i n thc blood-
strcam, and cortisol, thc most important of thcsc hormoncs, is practically
toxic to ncurons in thc most important mood-rcgulation ccntcr of thc brain,
thc hippocampus. So it fllows rathcr obviously that pcrsons with bipolar
disordcr should avoid thc kinds of strcss that incrcasc thcir cortisol lcvcls.
And what arc thosc strcsscs Thcy arc all thosc things that your doctor [and
probably your mothcr) told you to avoid. an unhcalthml dict, not cxcrcising,
smoking, drinking alcohol, not gctting a good night's slccp-wcll, you gct
thc idca. And although zcbras don't worry about hnancial problcms, dcad-
lincs, or rclationship conflicts, humans do. Thosc things incrcasc cortisol
lcvcls as wcll. In thc chaptcrs of part I\ I'll talk about how to put this knowl-
cdgc into practicc.
BpoIar sordcr and HormonaI Systcms
5y fr thc most important hormonc systcms in thc rcgulation of mood
arc thc thyroid hormoncs and thc adrcnal hormoncs. Wc'vc alrcady dis-
cusscd both of thcsc systcms a bit, but a bricf rcvicw will hclp.
Thc thyroid gland, locatcd just bclow thc larynx [thc "voicc box) at thc
basc of thc ncck, sccrctcs scvcral hormoncs into thc blood. Thcsc hormoncs
arc vcry important in thc body's rcgulation of cncrgy. Thyroid hormoncs
hclp control thc ratc of caloric consumption by thc body, known as mc|u|-
o||sm, and thc ratc at which calorics arc convcrtcd to and storcd as ft. If
thc thyroid gland sccrctcs an cxccss of its hormoncs [h}crthyroidism) , thc
pcrson`s mctabolism spccds up, if not cnough is sccrctcd [h}othyroidism) ,
thc mctabolism slows down. This "spccding up or "slowing down`' ahccts
cmotions and bchavior as wcll and can causc symptoms mimicking a mood
disordcr cvcn i n pcrsons who othcrwisc don`t sccm to havc mood problcms
[tablc i8- i ) .
Whcn a pcrson i s suhcring hom scvcrc hypcr- or hypothyroidism,
thc clinical picturc is prctty unmistakablc. 5ut in mild thyroid problcms,
changcs in mood and activity lcvcl can bc thc on|} symptoms of thc thyroid
troublcs. ot only can thyroid discasc causc mood symptoms dircctly, it can
also makc thc symptoms of a prccxisting mood disordcr morc dimcult to
trcat. Wc havc alrcady discusscd thc link bctwccn rapid- cycling bipolar dis-
ordcr and thyroid discasc. Mood disordcrs can bc vcry rcsistant to trcatmcnt
if thcrc is cvcn thc slightcst thyroid problcm. Thcsc arc morc rcasons why
202 M NV11LiS, L\SS, i1 LLiiL1LiS
Tzeiri8-i Psychiatric symptoms of thyroid discasc
Poor concentration
Delusional thinking
Depressed mood
Poor concentration
Slowed thinking
Apathy and social withdrawal
it is vcry important to pay attcntion to this hormonal systcm and to tcst fr
thyroid hormonc lcvcls in pcrsons with mood disordcrs.
Tc adrcnal glands sit atop thc kidncys in thc lowcr back and sccrctc
many hormoncs, thc most important of which arc thc corticostcroids. Wc'vc
discusscd onc of thcsc, cortisol, in somc dctail. In addition to thcir rolc in
thc strcss rcsponsc, thc corticostcroid hormoncs arc vcry important in thc
rcgulation of mctabolism.
Corticostcroids arc potcnt anti- inflammatory agcnts, and many phar-
maccutical products, such as cortisonc, prcdnisonc, and othcrs arc artihcial
vcrsions of thcsc adrcnal hormoncs. Tcsc drugs arc a componcnt in somc
crcams uscd to trcat allcrgic skin rcactions, but corticostcroids arc also givcn
orally and intravcnously to trcat inflammatory conditions such as rhcuma-
toid arthritis, asthma, and inflammatory bowcl discasc, and thcy arc ohcn
givcn as a trcatmcnt fr acutc pain, cspccially back pain.
n onc hand, cxccssivc corticostcroids hom adrcnal tumors can causc
symptoms of agitatcd dcprcssion with suicidal thinking. n thc othcr hand,
hypomanic symptoms sccm to bc morc common in paticnts bcing trcatcd
with artihcial corticostcroids fr mcdical conditions . Pcrsons with bipolar
disordcr nccd to bc vcry carcml about taking thcsc drugs fr mcdical con-
ditions and should ask about altcrnativcs whcn such trcatmcnt is bcing con-
sidcrcd. [Stcroid crcams do not causc psychiatric symptoms. Tc crcams arc
frmulatcd so that thc mcdication ahccts only thc tissuc it comcs into dircct
contact with. nly minutc amounts of thc activc ingrcdicnt arc absorbcd
into thc bloodstrcam. )
Pcturng BpoIar sordcr n thc Bran
Ior dccadcs clinical scicntists havc scarchcd fr a way to tcst fr bi-
polar disordcr. As wc havc dcvclopcd morc sophisticatcd ways of probing
thc workings of thc brain, wc havc bccn ablc to mcasurc subtlc dihcrcnccs
1PL1V 1L1LLY M 20j
in brain mnctioning in mood- disordcr paticnts, and although nonc of thcsc
obscrvations havc lcd to thc dcvclopmcnt of rcliablc tcsts yct, wc arc ncvcr-
thclcss lcarning a grcat dcal about thc disordcr with thcsc tcchnigucs.
As wc saw in chaptcr q, carly rcscarchcrs who disscctcd thc brains of dc-
ccascd pcoplc who had had bipolar disordcr or cxamincd thcir brain tissucs
undcr a microscopc fund no abnormalitics of brain structurc and gucs-
tioncd whcthcr bipolar disordcr was rcally a brain discasc at all. Wc now
know that it is-but that's bccausc wc havc lcarncd how to look fr and mca-
surc abnormalitics of brain cbcm|s|ry. Looking at thc s|ruc|urcof thc brain,
whcthcr with thc nakcd cyc, thc microscopc, or thc x-ray machinc, has bccn
unrcvcaling until guitc rcccntly. 5ut now two ncw imaging tcchnigucs arc
bcginning to allow us to picturc bipolar disordcr in thc brain.
Thc hrst of thcsc tcchnigucs i s maync||crcscnancc|may|ny or MRIMRI
i s bascd on thc discovcry that thc atoms of obj ccts placcd i n a powcrml
magnctic hcld absorb cncrgy or "rcsonatc at charactcristic hcgucncics that
can bc mcasurcd with thc propcr cguipmcnt. In mcdical MRI scans, thc
paticnt lics cncirclcd by a largc doughnut- shapcd instrumcnt that gcncratcs
a powcrml magnctic hcld. Scnsitivc instrumcntation mcasurcs thc dihcrcnt
rcsonanccs of dihcrcnt tissucs. bonc, musclc, ft, blood, and so frth, and
thc signals hom cach arc asscmblcd by computcr into a picturc. MRI is a
vcry scnsitivc tcchniguc, and cvcn small and subtlc tissuc dihcrcnccs show
up with astonishing clarity.
A numbcr of studics havc shown that thc brains of pcrsons with bipo-
lar disordcr show an incrcascd numbcr of unusual MRI hndings callcd 1,
bycr|n|cns|||cs. Thcsc arc small arcas of high MRI signal intcnsity thought
to indicatc changcs of watcr contcnt in brain tissuc. MRI scans of pcrsons
with blood-vcsscl discascs of thc brain and scvcral othcr brain discascs also
indicatc T_ hypcrintcnsitics, and T_ hypcrintcnsitics sccm to incrcasc with
thc normal aging proccss. 5ut although T_ hypcrintcnsitics arc not uniguc
hndings in bipolar disordcr, thcy arc fund in highcr numbcrs in pcoplc
with bipolar disordcr than in control subj ccts matchcd fr agc. In onc study,
hypcrintcnsitics wcrc fund i. e timcs as ohcn in bipolar I as in bipolar II
paticnts and twicc as ohcn in bipolar I paticnts as in comparison subj ccts
who did not havc bipolar disordcr.'
It's not clcar cxactly what is rcprcscntcd by thcsc signal dihcrcnccs on
thc MRI imagcs of pcrsons with bipolar disordcr. Most of thc othcr con-
ditions in which T_ hypcrintcnsitics arc fund involvc loss of ncurons and
othcr brain cclls and also thc pathological proccss callcd dcmyclination, thc
loss of thc ftty insulating matcrial of ncrvc hbcrs . Pcrhaps T_ hypcrintcnsi-
tics arc a rcsult rathcr than thc causc of bipolar disordcr, pcrhaps pcrmancnt
brain changcs occur ahcr many ycars and many cpisodcs of bipolar disor-
20q M NV11LiS, L\SS, i1 LLiiL1LiS
dcr symptoms, and T _ hypcrintcnsitics arc thc tiny "scars of thcsc cpisodcs.
Much work rcmains to bc donc to cxplain thc signihcancc of thcsc intrigu-
ing hndings.
Morc rcccntly, anothcr frm of MRI imaging has bccn dcvclopcd that
has rcvolutionizcd thc hcld of brain imaging. Iunc||cna| MRI [hRI) is a
tcchniguc in which thc MRI instrumcnt is adjustcd so that it can mcasurc
thc amount of oxygcn in arcas of thc brain in cxguisitc dctail. In this way,
not only is thc structurc of thc brain rcvcalcd, but variations in thc lcvcl of
mctabolic activity of brain arcas can bc visualizcd. Iunctional MRI scans
can pinpoint changcs in activity in brain arcas only a fcw cubic millimctcrs
in sizc that last only a sccond or two.
Whilc thcsc arc carly days in using this approach to undcrstand bipo-
lar disordcr, various basic fcts arc cmcrging. As might bc cxpcctcd, scv-
cral ccntcrs dccp in thc oldcst part of thc brain that arc alrcady known to
bc important in strong cmotions such as fcar and angcr [a sct of structurcs
known collcctivcly as thc ||m||csys|cm)show dihcrcnccs in activity in bipo-
lar paticnts comparcd t o hcalthy controls. I n addition, howcvcr, i t has bccn
fund that arcas of thc prchontal lobcs also show pattcrns of activity that
arc dihcrcnt in individuals with bipolar disordcr , thcsc arc arcas of thc brain
whcrc advanccd intcllcctual proccssing takc placc. nc of thc most consis-
tcnt hndings in hRI studics of mood disordcrs is a dccrcasc in mctabolic
ratc in an arca of thc lch prchontal lobc in dcprcsscd paticnts, a hnding that
lcd to thc dcvclopmcnt of transcranial magnctic stimulation [ TMS) , onc of
thc brain-stimulation trcatmcnts discusscd prcviously. Somc ncuroimaging
studics of bipolar disordcr havc fund a similar pattcrn of undcractivity in
this arca, but othcrs havc not, suggcsting that "unipolar dcprcssion and bi-
polar disordcr havc dihcrcnt biological bascs. '
Yct anothcr ncw frm of MRI ncuroimaging is callcd d_s|cnmagnctic
rcsonancc imaging [dMRI ) . This tcchniguc visualizcs watcr molcculcs as
thcy movc along brain conncctions and can rcvcal variation in thc conncc-
tions bctwccn dihcrcnt brain arcas. Studics using this approach havc fund
dihcrcnccs in thc sizc of connccting bundlcs of hbcrs connccting dihcrcnt
ccntcrs of thc limbic systcm in pcrsons with bipolar disordcr.
curoimaging in psychiatric illncss is a rclativcly ncw hcld, but rcscarch
in this arca is booming. It's dimcult to kccp up with thc dcvclopmcnt of ncw
imaging tcchnigucs, lct alonc thc ncw hndings that cmcrgc hom thcir usc.
Lnfrtunatcly, thc mctabolic pattcrns sccn in thcsc studics arc apparcnt only
whcn groups of individuals arc comparcd, most of thc studics comparc a
dozcn or so individuals with bipolar disordcr to a similar numbcr of hcalthy
controls to dctcct dihcrcnccs. Thc dihcrcnccs arc too small and thc rangc of
normal rcsults too largc fr thcsc approachcs to bc hclpml fr clinical pur-
1PL1V 1L1LLY M 20j
poscs such as frming thc basis fr a rcliablc tcst fr bipolar disordcr-so fr,
at lcast. 5ut thcsc hndings show conclusivcly that bipolar disordcr is a brain
discasc with rcal physical changcs in thc mnction of brain arcas that can bc
visualizcd and mcasurcd with thc right cguipmcnt.
20 M NV11LiS, L\SS, i1 LLiiL1LiS
L M A 1 H
1O1d1 I1SO1UO1 dDU L1Od11V11j
somc touch of madncss'' Most truisms contain a kcrncl of truth, and that
of thc "mad gcnius sccms to as wcll. Scholars who havc studicd thc livcs of
highly crcativc pcoplc havc discovcrcd that among thcm thcrc arc uncxpcct-
cdly high numbcrs of individuals with scvcrc psychiatric illncss. Clinicians
involvcd in this work havc concludcd that bipolar disordcr is by fr thc most
common of thcsc illncsscs. It docsn`t rcguirc cxtcnsivc rcscarch to comc up
with a long list of writcrs, artists, and composcrs whosc biographics indicatc
that thcy probably had a mood disordcr. Lct's takc a glimpsc into thc livcs of
scvcral of thcm.
Ccorgc Cordon, Lord 5yron [ I;88-I8z() [hgurc I- I) , had pcriods of
hcry cxpansivcncss and hollow dcspair throughout his lifc. Thc rccordcd ob-
scrvations of his hicnds and his physicians makc a diagnosis of bipolar dis-
ordcr all but ccrtain in thc grcat Lnglish poct. Lord 5yron's fmily history is
cntircly consistcnt with thc diagnosis of bipolar disordcr-suicidc, "mad-
ncss,' and murdcr can bc traccd back fr scvcral gcncrations on both sidcs
of his fmily trcc.
Mcdical biographcrs of Vinccnt van Cogh [I8y -I8o) havc spcculatcd
fr dccadcs about thc illncss that drovc him to sclf- mutilation and rcpcat-
cdly conhncd him to thc Asylum of Saint Paul at Saint- Rmy. Thc cpisodic
naturc of van Cogh`s illncss and thc accclcration of its coursc toward thc cnd
of his lifc arc highly suggcstivc of bipolar disordcr. Van Cogh dcscribcd his
drcadml dcprcssions in his lcttcrs and was diagnoscd with mania by scv-
licuarIp- I Ccorgc Cordon, thc Lnglish poct usually known as Lord 5yron,
sudcrcd hom scvcrc mood symptoms throughout his lif [as did scvcral mcm-
bcrs of his fmily) . "I must think lcss wildly,` hc wrotc in his cpic Cb||deHar-
c|dsP||yr|maye "I havc thought too long and darkly, till my brain bccamc . . . a
whirling gulf of phantasy and hamc``
Scurce CuIvcr Icturcs, !nc.
cr al of his physicians. Van Cogh`s fmily history, likc Lord 5yron`s, sccms to
conhrm thc diagnosis of bipolar disordcr . Vinccnt's brothcr To dcscribcd
his own strugglcs with dcprcssion in lcttcrs to Vinccnt, and a third brothcr,
Cor, committcd suicidc. A pcrson nccds only to imaginc thc brilliant, swirl-
ing, somctimcs hcnzicd colors and shapcs of van Cogh`s paintings as visual
rcprcscntations of his moods to undcrstand what psychiatric illncss bcst cx-
plains thc artist's cpisodcs of psychosis .
Tc Romantic composcr Robcrt Schumann [I8Io-I8y 6) wrotc of suicidc
at agc cightccn, but only a ycar latcr rcportcd, "I am so mll of music, and so
ovcrflowing with mclody that I hnd it simply impossiblc to writc down any-
thing' Schumann suhcrcd his hrst maj or cpisodc of psychiatric illncss in
I8(( at thc agc of thirty-fur, but hc had writtcn a dcscription of his dcprcs-
sions scvcral ycars carlicr in a lcttcr to his mturc wifc, Clara. "o onc knows
thc suhcring, thc sickncss, thc dcspair, cxccpt thosc so crushcd. In my tcrri-
blc agitation I wcnt to a doctor and told him cvcrything-how my scnscs
filcd mc so that I did not know which way to turn in my hight, how I could
not bc ccrtain of not taking my own lifc whcn in this hclplcss condition'
20 M NV11LiS, L\SS, i1 LLiiL1LiS
Schumann rccovcrcd hom this cpisodc to writc somc of his grcatcst musical
works, including thrcc of his fur symphonics, but tcn ycars latcr hc suhcrcd
anothcr collapsc. In Icbruary I8y( Clara rccordcd, "In thc night, not long
ahcr wc had gonc to bcd, Robcrt got up and wrotc down a mclody which, hc
said, thc angcls had sung to him. Thcn hc lay down again and talkcd dcliri-
ously thc wholc night. Whcn morning camc, thc angcls transfrmcd thcm-
sclvcs into dcvils and sang horriblc music, tclling him hc was a sinncr and
that thcy wcrc going to cast him into Hcll''
A fcw wccks latcr, probably in thc grip of an cpisodc of psychotic dcprcs-
sion, Schumann ran out of thcir homc and thrcw himsclf oh a bridgc into
thc icy watcrs of thc Rhinc. Hc was rcscucd by hshcrmcn and placcd in thc
asylum in Lndcnich, whcrc hc dicd a ycar latcr, possibly of sclf-starvation.
As with van Cogh, biographcrs havc guarrclcd at timcs about Schumann`s
diagnosis, but a glancc at thc opus numbcrs of his works groupcd by ycar
of composition [hgurc I- z) lcavcs littlc doubt that hc suhcrcd hom bipolar
disordcr. What othcr illncss could bcttcr cxplain thcsc intcnsc fluctuations
of productivity, pcriods of intcnsc crcativc cncrgy that gavc way to psychosis
and dcspair
Thc fct that many grcat artists havc suhcrcd hom bipolar disordcr docs
not in itsclf indicatc a spccial link bctwccn bipolar disordcr and crcativity.
Thcrc havc ccrtainly bccn many othcr grcat artists, writcrs, and composcrs
who as fr as wc can tcll did nc|suhcr hom major psychiatric illncsscs. [o-
hanncs 5rahms, Schumann's musical protg, who arguably wcnt on to sur-
pass his mcntor's accomplishmcnts as a composcr, was as staid and stcady a
man as cvcr livcd. 5rahms atc dinncr at thc samc rcstaurant in Vicnna ncarly
cvcry day fr thc last scvcral dccadcsof his lifc, ohcn sitting at thc samc tablc
and ordcring thc samc itcms hom thc mcnu.
cvcrthclcss, scvcral rcscarchcrs who havc pcrfrmcd psychobiograph-
ical survcys of groups of crcativc individuals havc fund that a striking and
inordinatc numbcr of accomplishcd artists, writcrs, and musicians havc suf-
fcrcd hom bipolar disordcr. Most studics havc comc up with prcvalcncc
ratcs of bctwccn o and yo pcrccnt-ncarly tcn timcs thc ratc of mood dis-
ordcrs in thc gcncral population. Pcrhaps thc most carcml of thcsc studics
has bccn donc by Kay Rcdhcld [amison, who cxamincd autobiographical
and biographical matcrials and, whcn availablc, thc mcdical rccords of all
major 5ritish and Irish pocts born bctwccn oy and I8oy. [amison con-
cludcd that ovcr half of thcsc writcrs suhcrcd hom a mood disordcr, morc
than onc-third of thcm hom bipolar disordcr. Thcsc numbcrs arc so high
that onc can`t hclp but wondcr if thcrc might bc somc bias in thc rcscarch
mcthod. do thc morc tumultuous biographics of psychiatrically ill artists
rcsult in morc biographical matcrial bcing availablc, thus skcwing thc rc-
sults To avoid such a bias, rcscarchcrs havc madc studics of living writcrs,
1PL1V 11SLV1V i1 LV1N1Y M 20
! 24
003 0! 0
! 42
! 27
030 ! 20
032 029 064
02! 027 054
022 0! 7 0! 8 026 052 047
0! ! 0! 4 0! 2 0! 6 025 038 044 050
007 00! 002 005 099 009 0! 3006 0! 5 024 027 04! 046
! 46
! 45
! 4!
! 38
! 37
! 08
! 06
! 02
! 0!
094 ! 36
093 ! 28
092 ! 2!
09! ! ! 9
086 ! ! 7
085 ! 44 ! ! 6
082 ! 30 ! ! 3
079 ! 29 ! ! 2 ! 43
078 ! 25 ! ! ! ! 34
076 097 ! ! 0 ! 33
075 096 ! 09 ! 48 ! 32
072 084 ! ! 5 074 090 ! 07 ! 47 ! 3!
080 08! 073 089 ! 05 ! 40 ! 26
065 07! 070 088 ! 04 ! 39 ! 23
065 06! 063 068 069 087 ! 03 034 ! ! 8
055 059 062 066 067 083 ! 00 ! 22 ! ! 4
! 829 '30 ' 3! '32 '33 ' 34 '35 ' 36 ' 38 '40 ' 4! '42 '43 '44 '45 '46 '47 '48 '49 '50 ' 5! '52 '53 '54


! 840

throughout! 844

! 849
iGURB p-z Thc scvcrc huctuations of thc Ccrman Romantic composcr
Robcrt Schumanns musical productivty bccomc strikingly apparcnt whcn his
musical works [idcntincd hcrc by opus numbcr) arc arrangcd according to thc
ycar of thcir composition. Schumann dicd in an asylum a littlc morc than a
ycar ahcr his suicidc attcmpt in 8](.
Scurce Adaptcd hom Lliot Slatcr and AlIrcd Mcycr, "Contributions to a IathoIogy oI thc
Musician Kobcrt Schumann, Ccn{n|a Ps)ch|a|r|ca 2 ) . 6-q. Kcproduccd with thc
pcrmission oI S. Kargcr, AG, bascl.
210 M NV11LiS, L\SS, i1 LLiiL1LiS

TzeirIp- I Artists, writcrs, and composcrs with bipolar disordcrs
Paul Gauguin
Vincent van Gogh*
Mark Rothko*
William Blake
Lord Byron
Ernest Hemingway*
Robert Lowell*
Sylva Plath*
Anne Sexon*
Virginia Woolf
Hector Berlioz
George Frederick Handel
Robert Schumann*
Hugo Wolf
*Attcmptcd or committcd suicidc.
musicians, and artists who wcrc sclcctcd bccausc thcy had won litcrary and
artistic prizcs. Tosc studics havc comc up with virtually thc samc numbcrs.
Tc prcvalcncc of bipolar disordcr is simply much highcr in groups of ac-
complishcd artists than in thc gcncral population [tablc I- I) . '
How can this striking hnding bc cxplaincd Lmil Kracpclin thought
that manic- dcprcssivc illncss could hcc a pcrson hom thc inhibitions that
might othcrwisc stiflc crcativity. "Tc volitional cxcitcmcnt which accom-
panics thc discasc may . . . sct hcc powcrs which arc othcrwisc constraincd
by all kinds of inhibition s] '' Icar of filurc, scnsitivity to criticism, worry
that onc has nothing important to contributc-thcsc kinds of inhibitions, of
coursc, vanish during pcriods of hypomania and mania.
nc can arguc that thc cxtraordinary mcntal statcs cxpcricnccd by pcr-
sons with bipolar disordcr providc thcm with rich raw matcrials fr thc pro-
duction of works of grcat crcativity. As I tricd to makc clcar in chaptcr 1 of
this book, thc clinical statcs of mania and major dcprcssion ohcn bcar littlc
rcscmblancc to normal mood statcs. Tcy arc not simply cxaggcrations of
normal happincss and sadncss but rathcr arc normal moods transccndcd
and transfrmcd. Is it any wondcr, thcn, that thosc who cndurc thcm havc
put such grcat chort into chronicling and communicating thcsc rcmarkablc
cxpcricnccs 5ccausc of thc rclapsing and rcmitting coursc of thc illncss, a
pcrson who has rccovcrcd hom mania or maj or dcprcssion can rccord what
1PL1V 11SLV1V i1 LV1N1Y M 211
it was likc. Individuals in thc midst of an cpisodc will usually bc too disorga-
nizcd or too lcthargic to bc vcry productivc, but latcr, whcn thcir mood statc
rcturns to normal, thcy can cxprcss thcsc almost incxprcssiblc fcclings and
cxpcricnccs in art, music, and poctry.
It has bccn suggcstcd that thc changcs in thinking pattcrns that occur
during thc hypomanic and manic statcs arc cspccially conducivc to crcativc
cndcavor. Whcn thc thinking proccsscs of highly crcativc individuals [with
or without mood disordcrs) havc bccn studicd, it has bccn fund that thcir
thinking tcnds to bc vcry fluid and divcrgcnt. Idcas spring hom and givc risc
to othcr idcas only looscly conncctcd by logic and convcntion. Lnrclatcd
idcas arc mcrgcd and minglcd in novcl ways. Thc loss of logical progrcssion
in thinking and a rapid flow of looscly conncctcd idcas arc, of coursc, a mn-
damcntal aspcct of thc hypo manic statc.
It has also bccn suggcstcd that it is not any onc mood statc, normal or
abnormal, that givcs risc to thc crcativc powcrs of thcsc artists, but rathcr thc
flux and tcnsions bctwccn thc dihcrcnt mood statcs. Constant changcs in
mood and tcmpcramcnt givc thc individual with cyclothymic mood changcs
a kalcidoscopic vicw of thc world, always changing, always ncw. Pcrhaps
bipolar disordcr stimulatcs crcativity in part bccausc its suhcrcrs cxpcricncc
thc world through thc cmotional prisms of its many and shihing moods,
somc of thcm cxtrcmc, cvcn violcnt. As thc Lnglish poct [ohn Kcats obscrvcd,
"What shocks thc virtuous philosophcr dclights thc chamclcon poct'`
Individuals with bipolar disordcr may bc drawn to crcativc cndcavors
out of a nccd to undcrstand and hcal thcmsclvcs through art and thc act of
crcation. Thc Ircnch author and hlmmakcr [can Coctcau said, "Art is sci-
cncc madc clcar'" Whcn mcdicinc and psychiatry fil to cxplain thc inncr
cxpcricnccs of thc discasc, whcn lithium and antidcprcssants and thcrapy
all floundcr and thc tcrriblc moods rcturn again and again, pcoplc can hnd
ways of undcrstanding and transfrming thcir suhcring through poctry,
music, and painting.
All thcsc rcasons hclp us to undcrstand why this drcadml and ohcn
dcstructivc illncss can also gcncratc such intcnsc crcativity and artistic ac-
complishmcnt. If crcativc work rcguircs uniguc cxpcricnccs, fluid imagina-
tion, conhdcncc in onc's abilitics, and cncrgctic cxcitcmcnt about thc act of
crcation, bipolar disordcr would sccm to ht thc bill.
5ut rcading thc biographics of thcsc bipolar artists rcvcals thc high
pricc thcy ohcn paid. 5ipolar disordcr was a mighty but malignant musc
fr Vinccnt van Cogh and Lrncst Hcmingway and Sylvia Plath, all of whom
committcd suicidc. How many morc symphonics would Robcrt Schumann
havc composcd if, likc his guict, stcady hicnd 5rahms, hc had livcd into his
Pcrhaps thc most intriguing gucstion about thc conncction bctwccn bi-
212 M NV11LiS, L\SS, i1 LLiiL1LiS
polar disordcr and crcativity is whcthcr or not thc illncss was somchow cs-
scn||a| to thc crcativc powcrs of thcsc individuals. Van Cogh might havc
livcd to paint many morc paintings if hc had not suhcrcd hom bipolar disor-
dcr, but would thcy havc bccn grcat paintings Would hc havc bccn a paintcr
at all r would hc havc acguicsccd to his fthcr's wishcs and contcntcdly
applicd himsclf to bccoming a mcmbcr of thc clcrgy This is, of coursc, an
unanswcrablc gucstion whcn historical hgurcs arc involvcd, but a rclatcd
gucstion poscs a vcry rcal dilcmma fr many individuals with bipolar disor-
dcr and thcir physicians. Oocs thc trcatmcnt of bipolar disordcr with mood-
stabilizing mcdication supprcss crcativity and dull thc artistic spirit
Scvcral studics attcmpting to answcr this gucstion wcrc donc just ahcr
thc introduction of lithium as a trcatmcnt fr bipolar disordcr in thc I;os
[onc of thcm by Morgans Schou, who, as you may rcmcmbcr hom chaptcr
q, was a pionccr in thc usc of lithium as a mood stabilizcr) . Artists and writ-
crs wcrc askcd whcthcr thcy thought trcatmcnt with lithium had incrcascd,
dccrcascd, or had no chcct on thcir productivity. Thc rcsults arc firly un-
cguivocal and pcrhaps a littlc surprising. vcr half [y; pcrccnt) rcportcd
that trcatmcnt of thcir mood disordcr with lithium had |ncrcascdthcir ar-
tistic productivity, and anothcr zo pcrccnt thought it had not ahcctcd thcir
artistic output. nly onc-guartcr of thcsc artists and writcrs fclt that lithium
had advcrscly ahcctcd thcir work. Sincc onc of thc sidc chccts of lithium in
somc pcrsons is a dulling of thinking, it is also possiblc that thcsc individ-
uals wcrc rcporting thc impact of a mcdication sidc chcct rathcr than thc
impact of mood stabilization. Would artists trcatcd with valproatc or carba-
mazcpinc havc rcportcd thc samc rcsults
vcr thc ycars a vcry fcw of my paticnts havc rcsistcd taking mood sta-
bilizcrs bccausc thcy fclt that thcir crcativc powcrs would bc or actually wcrc
advcrscly ahcctcd by thcsc mcdications. I havc usually thought that thcsc
individuals wcrc rcluctant to takc mcdications fr othcr rcasons. unwilling-
ncss to acccpt a diagnosis of bipolar disordcr, ambivalcncc about taking a
mcdication that thcy fclt would "control thcm, and othcr undcrstandablc
conccrns that can usually bc rcsolvcd with thcrapy and counscling [scc
chaptcr zo fr morc discussion of thcsc issucs ) . Pcoplc scizc upon all kinds
of rcasons not to takc mcdication, my imprcssion is that this particular plau-
siblc- sounding rcason is usually a substitutc fr fcing and working through
undcrstandably conflictcd fcclings about taking mcdication.
Thc mystcrious link bctwccn bipolar disordcr and crcativity, though un-
cxplaincd by cithcr psychiatrists or philosophcrs, is rcal. It poscs challcngcs
fr paticnts and dilcmmas fr clinicians and ohcrs opportunitics fr rc-
scarchcrs. 5cttcr undcrstanding of this conncction will not only cxpand our
undcrstandings of mood disordcrs but will pcrhaps lcad us to ncw insights
into thc magic of artistry and thc crcativc proccss.
1PL1V 11SLV1V i1 LV1N1Y M 21j
A H 1
!J! LJ
.J ^.`J! Y
Thcrc arc millions of pcoplc living with bipolar disordcr today. Many
arc living hcalthy, happy, and productivc livcs, but many othcrs arc
not. This scction of thc book is intcndcd to hclp you to maximizc your
chanccs of gctting into and staying in thc hrst catcgory and staying out
of thc sccond.
If you'rc looking fr a simplc list of dos and don`ts, I' m ahaid you
will bc disappointcd. Instcad, in chaptcr 2O, "Living with 5ipolar Ois-
ordcr,' I'vc tricd to lay out gcncral principlcs that undcrlic thc sorts of
advicc and rccommcndations that arc usually givcn to paticnts in thc
doctor's omcc or clinic. I hopc that ahcr rcading this chaptcr, you'll
havc a bcttcr undcrstanding of why somc of thc rccommcndations that
you hcar hom your doctor and thcrapist arc so important.
Chaptcr 2I ohcrs somc principlcs fr dcaling with cmcrgcncics
and highlights thc typcs of cmcrgcncy situations that paticnts and
thcir fmilics ohcn fil to prcparc fr. Wc'rc always tcmptcd to put oh
thinking about and planning fr things wc hopc won`t happcn. 5ut it is
important not to givc in to this tcmptation. I cxplain hcrc how casy it
is to bc prcparcd fr cmcrgcncics.
5ipolar disordcr docsn`t ahcct only thc individual with thc diagno-
si s of thc illncss. Incvitably, fmily and hicnds arc ahcctcd i n countlcss
ways, both dircctly and indircctly. Chaptcr 22, "Thc Rolc of thc Iam-
ily,' addrcsscs this aspcct of thc illncss. I talk about what fmily mcm-
bcrs can do-and, just as important, what fmily mcmbcrs cannot and
should not try to do-to hclp thcir lovcd onc who has bipolar disordcr.
A short hnal chaptcr looks into thc mturc at somc of thc cxciting
possibilitics that wc hopc will hclp us to bcttcr undcrstand bipolar
disordcr, to bcttcr diagnosc and trcat it, and, ycs, pcrhaps onc day to
LML this illncss.
21 M L1iL V i1 SY1iL 11
L M A 1 H 2
I1V1Dg W11D 1O1d1 I1SO1UO1
bipolar disordcr that works fr cvcryonc. Thc symptoms of thc illncss i n a
spccihc pcrson arc ohcn as uniguc as thc individual, and trcatmcnt must bc
carcmlly individualizcd t o cach paticnt and his particular symptom pattcrn.
This said, thcrc arc somc approachcs and picccs of advicc that I think arc
always going to bc hclpml. In fct, thc principlcs I lay out in this chaptcr arc,
in my cxpcricncc, indispcnsablc to staying wcll and having thc bcst possiblc
control of symptoms.
ConHont and Acccpt thc IIIncss
Thcrc is no curc fr bipolar disordcr, only trcatmcnt and managcmcnt.
It is a rclcntlcss illncss whosc symptoms incvitably and rcpcatcdly rcturn to
tormcnt its suhcrcrs. Thc only way to kccp it at bay is fr thc paticnt to bc
rclcntlcss as wcll-rclcntlcss about gctting nccdcd trcatmcnt and sticking to
it. o othcr piccc of advicc I can givc is as important as this onc.
Human bcings havc an almost unlimitcd capacity to cxplain away thc
obvious. Pcoplc who don`t want to conhont scrious physical illncsscs can
ignorc and cxplain away cvcn thc most alarming symptoms. fr cxamplc, thc
middlc- agcd man with a history of high blood prcssurc who docsn`t pay at-
tcntion to his rcpcatcd cpisodcs of chcst pain ["h, it's just hcartburn, must
havc bccn somcthing I atc) and thc woman who fccls a lump in hcr brcast
and tclls hcrsclf, "It's probably just a cyst, I'm surc it will go away' Conhont-
ing a possibly lifc- thrcatcning illncss is pcrhaps thc most hightcning cxpc-
ricncc wc can fcc. Small wondcr that wc somctimcs put oursclvcs through
somc imprcssivc mcntal gymnastics to avoid thc conhontation.
Whcn thcrc arc no bys|ca|signs of illncss, no pains or lumps or dizzy
spclls, it may bc all thc casicr to convincc oncsclf that thc symptoms of ill-
ncss arc somcthing clsc. I don`t know how many timcs I'vc had a paticnt ask
if I thought shc rcally nccdcd to continuc on a mood stabilizcr ahcr a manic
cpisodc had rcsolvcd. "Ahcr all, I was undcr a lot of strcss, and I hadn`t slcpt
fr wccks. Maybc I just nccd to takc it casy' As wc'll scc, strcss can indccd
play a rolc in prccipitating an cpisodc of a mood disordcr, |u| ||s nc| |bc
causc. Strcss docsn`t makc pcoplc manic or scnd thcm into a maj or dcprcs-
sion unlcss thcy havc bipolar disordcr. cithcr docs drinking too much or
slccp dcprivation or thc loss of a job or thc cnd of a lovc ahair or thc hundrcd
othcr things that you can convincc yoursclf cxplain your symptoms bcttcr
than a diagnosis of bipolar disordcr.
Pcoplc with bipolar disordcr can go through ycars of dcnial and angcr
about thcir illncss. I havc sccn paticnts rcpcatcdly stop taking mcdication
and drop out of trcatmcnt and cxplain thcir rcpcatcd hospitalizations, shat-
tcrcd rclationships, and ruincd hnanccs in all sorts of ways. "My wifc has
it in fr mc, shc put mc in thc hospital again' "If my boss wouldn`t put so
much prcssurc on mc, this wouldn`t happcn' "I think you nccd to chcck
my thyroid again, I know that's thc rcal problcm' r in its simplcst frm. "I
don`t nccd this mcdicinc, bccausc I'm not crazy'
If you havc bccn diagnoscd with bipolar disordcr and you havc rcad to
this point in thc book, you havc almost ccrtainly gottcn past a grcat dcal of
this undcrstandablc dcnial and angcr. This is a trcmcndous accomplishmcnt
and signals a turning point in your rccovcry. [If you'rc rcading this book to
bcttcr undcrstand anothcr pcrson with bipolar disordcr who hasn't yct madc
it past dcnial, chaptcr 22 is cspccially fr you. ) 5ut thcrc's a gap bctwccn
complctc dcnial and complctc ability to conhont and acccpt this illncss. Ln-
frtunatcly, pcoplc somctimcs try to hold on to thc notion that nothing is
scriously wrong by rcmsing to takc thc problcm scriously. It is cspccially
casy and cspccially problcmatic to takc this vicw in bipolar disordcr.
In bipolar disordcr thc paticnt ultimatcly dctcrmincs how wcll anytrcat-
mcnt is going to work-bccausc it is thc a||cn| who puts trcatmcnt rcc-
ommcndations into action. It is thc paticnt who will dctcrminc whcthcr hc
takcs cvcrydosc of mcdication, or just Opcrccnt of thc doscs, or Opcrccnt,
or cvcn lcss. Thc paticnt will dctcrminc whcthcr thc blood fr hcr lithium or
valproatc blood- lcvcl tcst is drawn cxactly twclvc hours ahcr thc last dosc,
or whcthcr shc gcts to thc lab tcn hours or hhccn hours ahcr thc last dosc,
throwing thc rcsults and thc doctor's calculations oh by IO pcrccnt or 2O
pcrccnt. Thc paticnt will dctcrminc how many appointmcnts arc kcpt with
21 M L1iL V i1 SY1iL 11
thc doctor and thc thcrapist and how many arc misscd, and how many arc
shortcr than schcdulcd bccausc of tardincss. It's so casy to lct your guard
down, lct trcatmcnt lapsc in littlc ways, and convincc yoursclf that miss-
ing a dosc of mcdication hcrc or thcrc, having that sccond bccr, ignoring a
string of slccplcss nights, isn`t rcally important. To do so is to turn away hom
rathcr than to conhont this discasc, and ohcn thc turning away springs hom
ambivalcncc about thc nccd fr trcatmcnt. |css |ban ccm|c|caccc|ancc c}
|bc d|ayncs|s. ot to acccpt this illncss, not to conhont it, puts trcatmcnt
succcss in jcopardy, bccausc in bipolar disordcr pcrhaps morc than in any
othcr scrious illncss, it is thc paticnt who administcrs thc trcatmcnt most of
thc timc.
Imaginc that a surgcon is cvaluating a paticnt with rccurrcnt abdom-
inal pain. Hc has donc a physical cxamination and has ordcrcd somc lab
tcsts and x-rays. All thc cvidcncc points to gall bladdcr problcms, and thc
surgcon dccidcs that thc bcst trcatmcnt among scvcral possibilitics is gall
bladdcr rcmoval. ow imaginc that thc surgcon is in thc middlc of thc opcr-
ation and suddcnly says to thc opcrating room nursc, "You know, this opcr-
ating room`s gctting awfully hot, and bcsidcs, I'm hungry. I think wc'll canccl
thc opcration. I'll givc our paticnt hcrc thc antibiotics fr anothcr wcck or
so. Maybc wc didn't stick with thc mcdication approach long cnough ahcr
all. Isn`t thcrc somc ncw mcdication that's supposcd to dissolvc gallstoncs
Maybc I'll ask Or. What's-his-namc about that. 5ut I just don't think I want
to go on with this opcration right now'
Sound fr-fctchcd [I ccrtainly hopc so | ) Wcll, hcrc's anothcr sccnario .
A man with bipolar disordcr has drivcn oh with thc fmily fr thcir thrcc-
wcck vacation. Thc family has alrcady travclcd hhy milcs whcn thc wifc says,
"Honcy, I packcd Timmy's asthma mcdicinc, but I didn't scc your mcdica-
tion bottlc in thc cabinct, did you rcmcmbcr to bring your lithium Thc
man rcalizcs that hc didn`t. `Ah . . . surc I did,' hc tclls his wifc, and thcn says
to himsclf, "Thrcc wccks won't makc any dihcrcncc. 5csidcs, I havcn`t fclt
dcprcsscd or anything in a long timc. This is a vacation, ahcr all. And if I gct
just a littlc high, it would bc K, I'm surc I could handlc it'
ow, what do thcsc sccnarios havc in common In both cascs, a trcat-
mcnt plan had bccn dccidcd upon, prcsumably ahcr much considcration and
discussion as to thc bcst coursc of action. In both cascs, somcthing comcs up
that makcs continuing with thc trcatmcnt a bit inconvcnicnt. In both cascs,
rathcr than makc a rational dccision about thc bcst coursc of action, thc
pcrson in chargc of thc trcatmcnt uscs flimsy logic-accompanicd pcrhaps
by a largc mcasurc of prccxisting ambivalcncc about thc trcatmcnt bcing thc
corrcct onc in thc hrst placc-to justify doing what's casicst. Add in somc
misinfrmation-thcrc |s no mcdication that dissolvcs gallstoncs, thrcc
wccks without lithium canmakc a dihcrcncc, and nobody can just "handlc
11N1iL 1H 1PL1V 11SLV1V M 21
cvolving mania-and you havc a rccipc fr disastcr. o onc would go back
to a physician who trcatcd him this way, and no onc should trcat himsclf
this way, cithcr.
I am suggcsting that making a commitmcnt to trcatmcnt mcans [I) bc-
ing activc, not passivc, i n frmulating a trcatmcnt plan with your providcrs,
[z) taking chargc of trcatmcnt implcmcntation Ioo pcrccnt of thc timc, and
[ ) making thc dccision that you will do cvcrything possiblc to takc control
of this illncss rathcr than bc controllcd by it.
5ut can a pcrson bc "on guard all thc timc In fct, who would wan|
to bc What kind of lifc is it to bc constantly worrying about onc's mcntal
hcalth A tcrriblc onc, of coursc. 5ut worrying all thc timc is ccrtainly not
what I' m suggcsting. Rathcr, acccpting and conhonting this illncss mcans
dcciding to do whatcvcr you nccd to do to bc as hcalthy as you can possi-
bly bc. This mcans sticking with trcatmcnt and bcing hank and opcn with
thc trcatmcnt profcssionals. It also mcans morc sclf- disciplinc and rcstraint
than you may bc uscd to, it mcans making somc lifcstylc changcs that I'll
call mccdbyy|cnc.
Practcc Mood Hygcnc
Hyy|cnc is a word that wc might not usc in mcdicinc as much as wc
should, and wc ccrtainly don`t usc it as much as wc uscd to. Hygcia was thc
Crcck goddcss of hcalth, thc daughtcr-or in somc vcrsions of thc story, thc
wifc-of Asclcpias, thc god of mcdicinc. Hygicnc, or hygicnics, is thc scicncc
of |bccs|a|||sbmcn| and ma|n|cnancc c} bca||bas opposcd to thc trcat-
mcnt of discasc-and has to do with conditions and practiccs that arc con-
ducivc to hcalth. Thc hygicnic conditions and practiccs wc think of today
usually rclatc to clcanlincss, but thc word has a much broadcr mcaning. At
thc bcginning of thc twcnticth ccntury, institutions such as thc [ohns Hop-
kins Lnivcrsity School of Hygicnc and Public Hcalth [now thc 5loombcrg
School) and thc London Lnivcrsity School of Hygicnc and Tropical Oiscascs
wcrc fundcd to study mcthods fr rcvcn||nydiscasc and fr promoting
and improving thc hcalth of wholc communitics. Prcdating thcm both was
thc Mcntal Hygicnc Association, fundcd in Io by frmcr asylum inmatc
Clihord 5ccrs [who probably had bipolar disordcr) . ow callcd thc Mcntal
Hcalth Association, its purposc is to promotc cmotional hcalth and wcll-
bcing and to lobby fr bcttcr and morc rcadily availablc trcatmcnt fr psy-
chiatric illncsscs.
So, what do I mcan by mccd byy|cncSimply put, practiccs and hab-
its that promotc good control of mood symptoms in pcrsons with bipolar
disordcr. Scvcral arcas of rcscarch on bipolar disordcr show how import-
ant prcvcntivc mcasurcs can bc fr improving symptom control in bipolar
220 M L1iL V i1 SY1iL 11
disordcr. Things likc strcss managcmcnt and lifcstylc rcgularity makc a big
Lmil Kracpclin noticcd that carly in thc coursc of his manic- dcprcssivc
paticnts' illncsscs, thcir mood cpisodcs ohcn camc on ahcr a strcssml cvcnt
in thcir livcs. "In cspccial, thc attacks bcgin not inhcgucntly ahcr thc illncss
or dcath of ncar rclativcs . . . . Among othcr circumstanccs thcrc arc occa-
sionally mcntioncd guarrcls with ncighbors or rclativcs, disputcs with lov-
crs . . . cxcitcmcnt about inhdclity, hnancial dimcultics . . . . Wc must rcgard
all allcgcd inj urics as possiblc sparks fr thc dischargc of individual attacks'
Kracpclin was guick to point out that thcsc cvcnts wcrc triggcrs, not causcs,
and that "thc rcal coursc of thc malady must bc sought in pcrmancnt intcr-
nal changcs which . . . arc innatc' Kracpclin noticcd, howcvcr, that latcr in
thc coursc of thc illncss, attacks occurrcd "wholly without cxtcrnal influ-
cnccs,' and hc proposcd that fr paticnts at that stagc of thc illncss, "cxtcrnal
influcncc s] . . . must not bc rcgardcd as a ncccssary prcsupposition fr thc
appcarancc of an attack''
Thc accuracy of thcsc obscrvations has bccn bornc out in latcr studics .
initial and carly mood cpisodcs in paticnts with bipolar disordcr arc ohcn
rclatcd to psychological strcssors, but ahcr scvcral cpisodcs, thc illncss can
takc on a lifc of its own, such that latcr cpisodcs arc morc likcly to arisc
An intcrcsting parallcl in animals can bc dcmonstratcd by rcpcatcdly
giving animals small doscs of stimulants such as cocainc. vcr timc, ani-
mals bccomc mcrcrathcr than lcss scnsitivc to thc stimulant, and rcpcatcdly
giving thc samc small dosc causcs |ncrcas|nyamounts of bchavioral stimu-
lation in thc animal. Whcn thcsc animals' brain cclls arc closcly cxamincd,
it is fund that a ccrtain gcnc that had not bccn activc prcviously had bccn
turncd on by thc rcpcatcd stimulant cxposurc. This samc gcnc can bc madc
to turn on by strcssing thc animals-by dcpriving thcm of watcr, fr cxam-
plc. This work with animals, showing that chcmical stimulation as wcll as
strcss can bring about long-tcrm changcs in bchavior-possibly through al-
tcrations in gcnc mnction-is thought by many cxpcrts to bc highly rclcvant
to thc study of bipolar disordcr.'
Scvcral dircct obscrvations of paticnts indicatc that a similar phcnomc-
non may occur in individuals with bipolar disordcr . [I) Paticnts somctimcs
show morc cnvironmcntally triggcrcd mood cpisodcs at hrst in thc coursc
of thcir illncss and morc spontancously occurring cpisodcs latcr. [z) Thcy
somctimcs show an accclcration in thcir illncss as thcy agc, with cpisodcs
occurring morc and morc hcgucntly as timc gocs on. [ ) Mood cpisodcs
makc paticnts morc scnsitivc to strcss and morc likcly to rclapsc than thcy
might othcrwisc bc. In a study of hhy-two paticnts with bipolar disordcr
fllowcd fr two ycars, thosc who rclapscd during thc timc of thc study wcrc
11N1iL 1H 1PL1V 11SLV1V M 221
much morc likcly to havc cxpcricnccd somc strcssml cvcnt. In this group of
paticnts, thosc with a grcatcr numbcr of prior cpisodcs wcrc mcrcscnsitivc
to thcsc strcsscs. thcy wcrc morc likcly to rclapsc undcr strcss, and thcy rc-
lapscd morc guickly.'
Thc convcrsc, howcvcr, may bc truc as wcll. as timc in rcmission gcts
longcr, pcoplc sccm to dcvclop a rcsilicncy that hclps thcm stay wcll. I prcvi-
ously rcpcatcd a collcaguc's commcnt that "thc sccond ycar on lithium`' was
bcttcr than thc hrst. Hcrc's a corollary. scvcral ycars ago, I was lcading a scm-
inar fr psychiatry rcsidcnts at [ohns Hopkins on thc trcatmcnt of bipolar
disordcr with lithium. Wc wcrc luc| cnough to havc my collcaguc Hop-
kins profcssor Kay [amison drop by and j oin us that ahcrnoon. As wc wcrc
hnishing up, I rcpcatcd my othcr collcaguc's maxim fr thc rcsidcnts, "Thc
sccond ycar on lithium i s bcttcr than thc hrst' Smiling, Or. [amison addcd,
"That's right . . . and thc |wcn|}-sccond ycar on lithium is just tcrrihc| Hcr
point was that longcr pcriods of mood stability confcr a kind of rcsilicncc
on pcrsons with bipolar disordcr and lcsscn thc probability that strcsscs will
triggcr an cpisodc. Scvcral studics havc dcmonstratcd that trcatmcnt and
thc prcvcntion of mood cpisodcs improvc thc long-tcrm outcomc in bipolar
disordcr. Trcatmcnt intcrvcntion during thc hrst tcn ycars ahcr diagnosis
appcars to bc cspccially important, thc prcvcntion of manic cpisodcs is vcry
important, too. ' Working hard to stay wcll, cspccially in thc hrst ycars ahcr
diagnosis, makcs it casicr to stay wcll ovcr thc longcr tcrm, put anothcr way,
"stability bcgcts stability' This mcans that onc of thc fundations of mood
hygicnc nccds to bc rc|ascrcvcn||cn. And thcrc should bc no doubt in
your mind at this point that thc most chcctivc rclapsc-prcvcntion tool is
Pcrsons with bipolar disordcr should makc pcacc with thc idca of taking
mcdication cvcry day fr thc frcsccablc mturc. That is an cspccially hard
thing to do in this discasc. Thc symptoms and thc nccd fr mcdication ohcn
start whcn pcoplc arc in thcir twcntics or cvcn youngcr, whcn nonc of thcir
pccrs havc to bothcr with mcdication-whcn thc only pcoplc thcy know
who takc mcdication arc "old pcoplc and "sick pcoplc' It's vcry dimcult
fr a young, physically hcalthy pcrson who's fccling wcll to takc mcdication
cvcry day.
Thc idca of taking mcdication to control onc's moods and mcntal pro-
ccsscs is also a daunting onc. An carly study askcd frty- scvcn pcrsons who
wcrc attcnding a clinic about thcir attitudcs toward taking lithium. ` f thosc
who had stoppcd taking lithium at somc point during thc coursc of thcir
trcatmcnt, thc most hcgucntly givcn rcason was that thcy wcrc "bothcrcd by
thc idca of moods bcing controllcd by a mcdication' n thc fcc of it, this
is guitc undcrstandablc, pcrhaps cvcn rcasonablc. Rcmcmbcr, howcvcr, that
222 M L1iL V i1 SY1iL 11
in bipolar disordcr thc mcdication allows thc paticnt to bc in control of hcr
moods rathcr than thc othcr way around.
Lach individual nccds to work out fr himsclf a mcthod fr making surc
that cvcry singlc dosc of cvcry mcdication is takcn. Pharmacics scll a varicty
of clcvcr dcviccs to hclp makc this happcn. Thcrc arc pillboxcs with built-in
clocks and timcrs, with alarms that can bc sct to go oh whcn it's timc fr thc
ncxt dosc. Thcrc arc boxcs that hold a wholc wcck`s worth of mcdication in
littlc compartmcnts, onc fr cvcry dosc, so that thc answcr to "Oid I takc my
dosc this morning is always clcar and ccrtain. if thc littlc compartmcnt is
cmpty, thc dosc was takcn. Ask your trcating physician if your mcdication
can bc takcn just oncc a day, or twicc rathcr than thrcc timcs a day. Ask
about controllcd-rclcasc frms of mcdications, scvcral arc availablc, ohcn
making it possiblc to climinatc midday doscs, which arc incvitably thc most
dimcult oncs to ht into a busy lifc.
Thc body of cvidcncc showing that mcdication prcvcnts rclapsc cannot
bc argucd with, it is simply ovcrwhclming. 5ut thcrc is somc cvidcncc that
pcrsons who stop mcdication fr bipolar disordcr may run morc than just
thc risk of a rclapsc. Thcrc havc bccn scvcral casc rcports of pcrsons who
stoppcd taking lithium fr bipolar disordcr, had a rclapsc, and|bcnd|d nc|
rcscnd|c|||b|umwbcn||wasrcs|ar|cd.ncc thc lithium had bccn stoppcd,
it did not work vcry wcll fr thcsc paticnts whcn thcy startcd back on it,
a phcnomcnon that has bccn callcd "lithium- discontinuation- induccd rc-
hactorincss' ut of hhy-fur paticnts who stoppcd lithium, tcn of thcm-
ncarly 2O pcrccnt-had a poor rcsponsc whcn thcy rcstartcd it. Ior thcsc
paticnts, lithium had lost somc of its chcctivcncss. " Thc rcsults of this study
providc cvcn morc proof of thc importancc of rclapsc prcvcntion fr thc
long-tcrm coursc of bipolar disordcr. I alrcady mcntioncd thc work show-
ing a bcttcr prognosis fr pcrsons whosc illncss is wcll controllcd hom thc
bcginning. Lithium- discontinuation- induccd rchactorincss illustratcs thc
convcrsc of thc adagc "stability bcgcts stability. |ns|a|||||y|cyc|s |ns|a|||||y,
at lcast in somc pcrsons .
cxt on thc list of mood- hygicnc practiccs is s|rcssandccn{|c|manayc-
mcn|.Most of us havc vcry littlc control ovcr whcn and how strcss and con-
flict comc into our livcs. 5ut wc can lcarn how to managc strcss and conflict
bcttcr-and hcrc I'll put in anothcr plug fr counscling and thcrapy. This is
bccausc I am talking about scrious, v|ycrcusattcntion to whatcvcr ongoing
sourccs of scrious strcss thcrc may bc. primary rclationship and marital con-
flicts, j ob and carccr problcms, and chronic hnancial or lcgal problcms arc
good cxamplcs. Immcdiatcly ahcr diagnosis with bipolar disordcr may not
bc thc timc to dcal with ongoing and chronic problcms of thcsc sorts. 5ut
scvcral months latcr, ahcr mood symptoms havc bccn undcr good control
11N1iL 1H 1PL1V 11SLV1V M 22j
fr a whilc, would bc a good timc fr somc vcry scrious stocktaking, and
profcssional hclp is highly rccommcndcd.
5y s|cc/|a/|ny I do not mcan somc proccss that can bc dcscribcd in
a fcw paragraphs or distillcd into thc kinds of "hclpml hints and "do and
don`t lists that you might hnd in a magazinc articlc. Rathcr, I mcan scr|cus
cxam|na||cn and}ndamcn|a| cbanyc. This may involvc changing j obs or
cvcn carccrs , sclling a housc you can't ahord, or dcclaring bankruptcy in-
stcad of struggling with an austcrity budgct, postponing or rcconsidcring
marriagc [or divorcc) , not going back to school. [ust as a pcrson who has had
a hcart attack would do somc scrious invcstigation and hard thinking bc-
frc taking a j ob as, say, a high-lcvcl managcr of a big company, thc bipolar
paticnt nccds to go through thc samc proccss bcfrc making big dccisions.
Thc strcss and strain involvcd in whatcvcr is bcing considcrcd should bc
scriously wcighcd in thc dccision-making proccss.
5ut scrious attcntion to thc "big stuh docsn't mcan that thc dctails of
cvcryday lifc will just takc carc of thcmsclvcs. S|ruc|ur|nyycur|{cis a vcry
important aspcct of mood hygicnc as wcll. In chaptcr I6 wc rcvicwcd thc
data and studics on thc rclationship bctwccn slccp and bipolar disordcr. Rc-
mcmbcr that a propcrly synchronizcd slccp-wakc cyclc is important to thc
rcgulation of mood and that pcriods of slccp dcprivation prccipitatc hypo-
manic and manic symptoms . s|a|||sb|nyands||c/|ny|c acrscna|scbcdu|c
is vcry important. This mcans cstablishing rcgular timcs fr going to bcd
and gctting up in thc morning-scvcn days a wcck, if possiblc.
Rcscarch on slccp shows that many othcr lifcstylc fctors contributc to
or dctract hom good slccp. Considcr cutting cahcinatcd bcvcragcs out of
your dict complctcly, or at lcast makc a rulc fr yoursclf not to drink cof-
fcc, tca [including iccd tca), or soh drinks containing cahcinc ahcr noon.
Hcavy mcals latc in thc day should bc avoidcd. Rcgular cxcrcisc has bccn
shown to bcncht slccp and has many othcr bcnchts as wcll, it hclps to stabi-
lizc blood prcssurc, fr cxamplc, most likcly bccausc of thc cortisol-lowcr-
ing chcct that rcgular cxcrcisc providcs. Scbcdu|cyour daily walk and your
Monday-Wcdncsday- Iriday swim or visit to thc gym. Oon't cxcrcisc only
whcn you "havc thc timc or "fccl likc it' Makc it part of your rcgular wcck,
not a luxury.
Dcn`|a||cwycursc{|crccras||na|c. Putting things oh until thc last mo-
mcnt invariably incrcascs strcss lcvcls . Waiting until thc clcvcnth hour to
work on your incomc tax rcturn and thcn staying up latc tankcd up on cof-
fcc, scarching fr rcccipts and W- z frms, is not somcthing pcoplc with bi-
polar disordcr should lct happcn to thcmsclvcs. It's no mn fr anybody, but
fr thc bipolar individual, it's downright dangcrous. Iilc your taxcs carly,
rcncw your drivcr's liccnsc carly, gct your car inspcctcd carly-you gct thc
22q M L1iL V i1SY1iL 11
idca. Lliminatc procrastination as a way of dcaling with things, and you'vc
gonc a long way toward climinating a lot of strcss. This advicc holds truc fr
putting oh dcaling with intcrpcrsonal problcms, too. Smoldcring tcnsions
in a rclationship, chronic conflicts with a co-workcr, a ncighbor, or a land-
lord-thcsc arc chronic strcsscs that will incvitably takc thcir toll on anycncs
mcntal hcalth and can cxact a highcr pricc on thc individual with a mood
disordcr. Oon't put oh dcaling with thcsc problcms, and i f you don`t know
how to approach thcm, gct thc profcssional hclp you nccd, whcthcr that
mcans consulting a counsclor or a thcrapist or an attorncy.
Alcohol As I'vc alrcady said, |bc|css, |bc |c||cr.
As I cxplaincd in a prcvious chaptcr, thc strcss hormonc cortisol has a
dircct injurious chcct on ncurons in thc hippocampus, an arca of thc brain
that is at thc ccntcr of mood control. Psychological strcss, slccp dcprivation,
lack of cxcrcisc, alcohol and drugs, and cvcn an unhcalthy dict arc all cnvi-
ronmcntal fctors that havc bccn shown to raisc cortisol lcvcls in thc blood.
Whatcvcr you can do to kccp cortisol lcvcls down is going to makc it casicr
fr your mcdication to work to kccp you wcll.
Somc pcoplc hnd it hclpml to kccp a rccord of thcir moods, a mccd
cbar|. This can bc a j ournal or diary if you'rc so inclincd, but simplcr and
lcss timc-consuming tcchnigucs can work just as wcll. If you nccd to kccp
an appointmcnt calcndar anyway, it's a simplc mattcr to makc a notation
of your mood cvcry day using a numcrical scalc. Clinicians commonly ask
paticnts to ratc thcir mood on a 1 to IOscalc, with 1 bcing thc most dcprcsscd
thcy'vc cvcr fclt, IO thc bcst mood thcy'vc cvcr had, and y a normal, ncutral,
cvcryday mood. If 1 to IO sccms too conhning, usc a scalc of 1 to IOO. It's
important to ratc your mood at thc samc timc cvcry day to control fr diur-
nal mood variations . Simply rccord your mood ratings cvcry day by j otting
down a numbcr in your appointmcnt book, rccording it in your computcr
timc-managcmcnt program, or marking it on a calcndar you kccp on your
bcdsidc tablc. nc of thc hrst things I ask my paticnts to do whcn wc'rc hav-
ing troublc with pcrsistcnt mood cycling is to kccp a morc dctailcd mood
chart that also capturcs changcs i n thcir slccp pattcrn, lcvcls of anxicty, and
mcdication changcs.
A guick Intcrnct scarch is all it takcs to hnd any numbcr of blank mood
charts you can casily print out. You will also hnd scvcral wcbsitcs that allow
you to sct up an account and track your symptoms onlinc, and mood-
trackcr apps fr smart phoncs arc availablc, too. Kccping this kind of rccord
will providc you and your clinical tcam with invaluablc infrmation that
can hclp show what mcdications arc or arc not working, dctcrminc whcthcr
thcrc is a prcmcnstrual or scasonal componcnt to mood changcs, and, of
coursc, dctcct cvolving dcprcssivc or hypomanic cpisodcs carly.
11N1iL 1H 1PL1V 11SLV1V M 22j
All of this is much casicr said than donc fr pcrsons with bipolar disor-
dcr. Rcgularizing your lifc in thcsc ways may sccm guitc frcign and strangc,
not to mcntion boring. If throughout your lifc you'vc lcarncd to wait fr
thc good moods to gct things donc and just put oh thinking about things
during thc incvitablc rcturn of thc bad oncs, such planning and rcgularity
won't comc casily. 5ut a growing body of rcscarch supports thc notion that
cxtcrnal rcgulators likc rcgular slccp and activity schcdulcs hclp with mood
BuId Your Support Systcm
Lvcryonc should havc a tcam of supportcrs and wcll-wishcrs to hclp hcr
gct through dimcult timcs. Pcrsons with bipolar disordcr arc no cxccption.
All of thc advicc I'vc givcn you so fr will bc much casicr to put into practicc
if you'vc got a tcam bchind you.
Thc most important mcmbcrs of thc tcam arc likcly to bc your fmily
and hicnds. A trustcd fmily mcmbcr or hicnd can bc cxtrcmcly hclpml by
acting as an objcctivc obscrvcr of mood changcs. nc problcm that pcrsons
with bipolar disordcr all strugglc with at onc timc or anothcr is dimculty
hguring out which mood changcs arc normal and which arc not. I havc sccn
paticnts go hom onc cxtrcmc to anothcr in this rcgard. Thcy may cxplain
away scvcrc and obviously pathological mood changcs as "normal ups and
downs whilc thcy arc in dcnial about thc illncss. Thcn thcy may ovcrrcact
and worry that cvcry low mood ahcr a disappointmcnt, cvcry cnthusiasm
ovcr a ncw proj cct or rclationship, mcans that thcir mcdication isn't work-
ing. Thc physician and thc thcrapist can hclp with this, of coursc, but somc-
onc who is conccrncd and caring and closcr to homc can bc an invaluablc
ally in this rcgard. An astutc hicnd or fmily mcmbcr who knows how to
communicatc obscrvations in a caring, nonprovocativc way upon noticing
sustaincd changcs in mood is onc of thc bcst supports you can havc. You
may nccd to givc thc pcrson you choosc pcrmission to bc blunt with you.
Thc bcst pcrson fr this task might not bc somconc who livcs in thc samc
housc with you, that pcrson may bc too closc to thc situation to bc objcctivc.
Look around you and choosc carcmlly.
This topic lcads to thc gucstion, To whom should you disclosc your
diagnosis Two good rulcs arc that thc disclosurc should bc madc only to
thosc who nccd |c /ncwand to thosc who can bc| and wan| |c bc|. Thc
"nccd to know catcgory includcs, of coursc, thc fmily doctor, all trcating
physicians, and any hcalth profcssional who might bc in a position to prc-
scribc mcdication-cvcn dcntists, fr cxamplc. If you havc an attorncy or
accountant who handlcs your ahairs on an ongoing basis, that pcrson prob-
ably nccds to know, too.
22 M L1iL V i1 SY1iL 11
With cmploycrs, things gct a bit trickicr. If you arc askcd to disclosc
conditions you arc bcing trcatcd fr as part of rccciving mcdical insurancc
or othcr bcnchts, thcn you nccd to disclosc your diagnosis . Iailurc to do so
can rcsult i n bcnchts bcing dcnicd at a latcr datc and claims fr rcimbursc-
mcnt of trcatmcnt costs not bcing paid. Oisclosurc up hont can avoid a lot
of problcms down thc linc, whcthcr this mcans sharing fcts about diagnosis
with a ncw cmploycr or with thc currcnt cmploycr at thc timc of diagnosis.
Lctting an cmploycr know that shih changcs, hcgucnt long busincss trips,
and latc hours arc things you will not bc ablc to takc on bccausc of a mcd-
ical condition is not only a rcasonablc rcgucst but also a workplacc right
protcctcd by thc Amcricans with Oisabilitics Act. I routincly writc lcttcrs
fr my paticnts who arc nurscs or othcrs who work night shihs, rcgucsting
that thcy not bc assigncd shih work-and rcminding thcm that thc AOA rc-
guircs thcm to providc "rcasonablc accommodations to cmployccs to kccp
thcm hcalthy. Your providcr will bc ablc to supply documcntation to support
such a rcgucst, too. 5asing thc cmploycr- cmploycc rclationship on opcnncss
and honcsty is always good policy. [Thc samc is truc fr all othcr rclation-
ships, of coursc. )
Although cmploycrs arc lcgally prohibitcd hom discriminating against
individuals with mcdical problcms in hiring and hring dccisions, thcy can
makc lifc dimcult fr cmployccs thcy want to gct rid of. "Choosc your bat-
tlcs would sccm to bc good advicc hcrc. If you scnsc hostility at your work-
placc toward pcrsons rccciving psychiatric trcatmcnt, you might bc doing
yoursclf a fvor to look fr a dihcrcnt cmploycr rathcr than fr an cmploy-
mcnt-law attorncy.
As fr pccrs and co-workcrs, thc "hclping critcrion would sccm to bc
thc applicablc onc, and carcml considcration is ncccssary hcrc. 5ut i f you
hnd that you'rc tclling co-workcrs about your diagnosis to gct sympathy,
to gct spccial considcration, or to gct out of unplcasant assignmcnts, you'rc
hcadcd fr troublc. Thcrc's no bcttcr way to brccd rcscntmcnt and conflict
on thc j ob. You don`t want to dcvclop a rcputation as onc of thosc pcoplc
who usc somc fctor bcyond thcir control to gct co-workcrs to covcr fr
thcm in various ways . That's not building a support systcm, it's manipula-
tion, and it will makc things worsc, not bcttcr.
I cannot spcak too highly of sucr|ycusfr pcrsons with mood dis-
ordcrs. Lndcr thc auspiccs of scvcral dihcrcnt national support organiza-
tions, hundrcds of groups providc support to thousands of individuals with
bipolar disordcr. [ Scc "Rcsourccs at thc cnd of this book fr infrmation on
thcsc organizations. ) Support groups organizcd by and fr individuals with
mood disordcrs and thcir fmilics not only providc pccr support but also arc
sourccs of accuratc infrmation about thc rcsourccs availablc in a particular
11N1iL 1H 1PL1V 11SLV1V M 22,
I somctimcs hcar a paticnt say that hc docsn't want to attcnd a support
group bccausc hc "docsn`t want to sit and listcn to othcr pcoplc's problcms'
Ccrtainly, sitting through an hour of whining is no mn and probably not
hclpml, but that's not what a support group should bc [if thc onc you hnd
yoursclf in is, think about starting to look fr anothcr group) . A good sup-
port group brings togcthcr individuals who sharc a common problcm and
want to lcarn hom cach othcr about coping with it bcttcr. It's onc thing to
ask your doctor about thc sidc chccts of a mcdication that you'rc contcm-
plating starting, but talking to somconc who is actually taking it fr thc
samc problcm you havc providcs a dihcrcnt and a vcry valuablc pcrspcctivc.
Within a support group, you may havc an opportunity to ask othcr pcrsons
with bipolar disordcr how |bcytold thcir boss or thcir childrcn about thcir
diagnosis, what |bcy do to rcmcmbcr a complicatcd mcdication schcdulc,
and a thousand othcr gucstions.
Anothcr advantagc of attcnding a support group is thc rcassurancc you'll
gct whcn you mcct othcr pcrsons with bipolar disordcr who arc doing wcll
and lcading hcalthy, happy, and productivc livcs. Oon't bc surpriscd, how-
cvcr, if thcsc flks sccm to bc in thc minority in your group. It's not that
doing wcll is a rarc outcomc, not at all. Rathcr, many pcrsons simply "out-
grow support groups as thcy do bcttcr and bcttcr. You can think of thcsc
flks as having gottcn what thcy nccdcd hom a support group and having
movcd on.
on' t Bc a "BpoIar Vctm"
Individuals with any incurablc but trcatablc mcdical problcm must lcarn
how to walk thc hnc linc bctwccn not taking thcir illncss scriously cnough
and taking it |cc scriously. Wc psychiatrists scc thc conscgucnccs of not
taking bipolar disordcr scriously cnough cvcry day in our omccs and clin-
ics-and, morc ohcn than not, in hospitals and cmcrgcncy rooms. Individ-
uals who stop taking mcdication, who won`t gct thc trcatmcnt thcy nccd
fr a substancc-abusc problcm, who ignorc ongoing cnvironmcntal strcsscs
and intcrpcrsonal problcms until thcy arc ovcrwhclmcd by thcm-thcsc in-
dividuals arc truly victims of bipolar disordcr who abdicatc to thc whims
and crratic rhythms of thcir illncss rathcr than do what thcy can to control
thcir symptoms. 5ut thcrc's anothcr kind of victim as wcll. thc pcrson who
worrics about hcr symptoms and illncss all thc timc, who avoids challcngcs
and withdraws hom work and thc community into a world of mcdications,
blood tcsts, doctor's visits, and support-group mcctings. I think most pcoplc
with bipolar disordcr spcnd somc timc on both sidcs of this hnc linc as thcy
sort out thc impact of thc illncss on thcir vicw of thcmsclvcs and hgurc out
how to intcgratc what thcy nccd to do about thc illncss into thcir lifcstylc.
22 M L1iL V i1 SY1iL 11
cithcr cxtrcmc is hcalthy, and it takcs timc, good advicc, and hard work to
hnd thc propcr balancc.
Pcrhaps thc biggcst obstaclc to hnding this balancc is s||ya.Sociologist
Lrving Cohman cxplaincd thc grisly origins of that word in thc introduction
to his I6 book on thc subj cct, S||ya:Nc|cscn|bcManaycmcn|c}Sc||cd
Idcn|||y:"Thc Crccks, who wcrc apparcntly strong on visual aids, originatcd
thc tcrm s||ymato rcfcr to bodily signs dcsigncd to cxposc somcthing un-
usual and bad about thc moral status of thc signihcr. Thc signs wcrc cut
or burnt into thc body and advcrtiscd that thc bcarcr was . . . a blcmishcd
pcrson, ritually pollutcd, to bc avoidcd, cspccially in public placcs' Cohman
originally bccamc intcrcstcd in thc issucs of stigma, prcjudicc, and discrim-
ination against physically handicappcd individuals who had somc immcdi-
atcly visiblc sign of bcing dihcrcnt. pcrsons who wcrc blind or dishgurcd or
who had had a limb amputatcd. Hc soon camc to rcalizc, howcvcr, that thc
samc issucs wcrc rclcvant, but bccamc much morc complicatcd, whcn thcrc
was no outward sign of thc stigmatizcd condition, as in "thc blcmishcs of
individual charactcr . . . mcntal disordcr, imprisonmcnt, addiction'
Iortunatcly, psychiatric conditions such as bipolar disordcr arc not ohcn
considcrcd "blcmishcs of individual charactcr anymorc, but thcy arc stig-
matizcd just thc samc. Pcrsons with psychiatric conditions arc too ohcn rc-
gardcd as untrcatablc and thus unprcdictablc and dangcrous, or at thc lcast
unrcliablc and incompctcnt. Too many hlms and tclcvision programs still
ridiculc or dcmonizc individuals with psychiatric illncsscs, and words likc
cracyand |nsancarc gcncralizcd tcrms of contcmpt that you can hcar in any
schoolyard during rcccss. Pcoplc with bipolar disordcr havc usually incor-
poratcd thcsc prcjudiccd and ncgativc vicws into thcir own way of thinking
hom a vcry young agc-a proccss psychologists rcfcr to as thc "intcrnaliza-
tion`' of stigma. Thcrcfrc, whcn thcy arc diagnoscd with bipolar disordcr,
thcy havc to dcal not only with thc prcjudiccs and unfir biascs othcrs may
havc toward thcm, but also with thcir cwn intcrnalizcd ncgativc idcas and
fcclings about pcrsons with a psychiatric illncss. Pcoplc can rcact to this in
oppositc ways, cithcr not acccpting thc diagnosis and rcmaining in dcnial
about it, or giving in to thcir ncgativc thinking and fcclings and bccoming
"a bipolar rathcr than "a pcrson who has bipolar illncss,' tclling cvcryonc
and anyonc about thcir illncss and using it as an cxcusc to avoid rcsponsi-
bilitics and challcngcs. In cithcr casc, thc individual has bccomc a victim of
thc illncss .
How can you avoid bccoming a victim You'vc takcn a big stcp by rcad-
ing this book. Accuratc infrmation about what bipolar disordcr is and is
not providcs an cxccllcnt dcfcnsc against prcjudiccd thinking and bad dc-
cisions bascd on misinfrmation. A closc sccond to gctting accuratc infr-
mation is gctting thc support, fccdback, and advicc-and thc opportunity
11N1iL 1H 1PL1V 11SLV1V M 22
to ask gucstions and just vcnt your fcars and hustrations-that counscling,
thcrapy, and support groups providc. o onc nccds to conhont this problcm
and sort through all thc conflicting cmotions and fcclings alonc-and no
onc should.
2j0 M L1iL V i1SY1iL 11
L M A 1 H 2
not thc dccisions wc would havc madc undcr othcr circumstanccs. Whcn an
cmcrgcncy ariscs fr which wc arc unprcparcd, wc usually havc to improvisc
a rcsponsc as wc go along. In this chaptcr I idcntify scvcral potcntial cmcr-
gcncics that may fcc thc individual with bipolar disordcr and his fmily
and discuss how to prcparc fr and dcal with thcm. nc of thc bcst ways to
prcparc fr an cmcrgcncy is to havc a crisis plan rcady bcfrchand.
5ccausc wc havc such chcctivc trcatmcnts availablc fr bipolar disordcr,
wc somctimcs frgct that it is a potcntially lcthal illncss. And whcn you arc
dcaling with a discasc that can bccomc lifc-thrcatcning, thc last thing you
want is an improviscd rcsponsc to an cmcrgcncy situation.
Pcoplc usually cnjoy making plans-vacation plans, wcdding plans, rc-
tircmcnt plans. Planning fr a psychiatric cmcrgcncy is much lcss cnj oyablc
but, unfrtunatcly, much morc important. Lnlikc vacation plans, thcsc arc
plans that no onc would bc disappointcd about not gctting to usc. 5ut if you
do nccd thcm, odds arc you'll bc vcry glad you madc thcm .

I could scnsc thc hustration in Lisa`s voicc as I listcncd to hcr spcaking
into thc cmcrgcncy- room phonc. Shc was a psychiatric nursc and wc
wcrc both at thc LR.
"I hcar you, ma`am, but thc magistratc won`t approvc a pctition fr
involuntary trcatmcnt just bccausc your husband isn`t taking his mcdi-
cation. I nccd morc infrmation bcfrc wc can-
Suddcnly shc stoppcd and put thc phonc down. "I can`t bclicvc it,
shc hung up on mc' Lisa lookcd down at hcr notcpad, thcn turncd to
mc. "Oocs thc namc Stanlcy Wintcrs mcan anything to you That was
his wifc. Shc wantcd somconc to comc out to thcir housc and bring
him in to thc cmcrgcncy room. Shc said hc's vcry dcprcsscd'
"Thc namc docsn`t ring any bclls with mc,' I rcplicd. "Lct's try thc
computcr to scc if hc's cvcr had any trcatmcnt hcrc bcfrc. Thcn wc
can try calling hcr back' As Lisa stcppcd ovcr to thc cmcrgcncy room`s
computcr tcrminal, I glanccd at my watch. "Lisa, I'm going to go grab
somc lunch. You know how to rcach mc'
Twcnty minutcs latcr, a tcxt hom Lisa arrivcd, a mcssagc to call
thc cmcrgcncy room.
"Irank, this is Lisa. Mr. and Mrs. Wintcrs arc hcrc in thc LR. Wcll,
that's not cxactly truc. Mrs. Wintcrs is hcrc, but Mr. Wintcrs won`t gct
out of thc car. Oo you think you could comc down
I hadn't donc any parking- lot thcrapy fr a whilc, and as I walkcd
past thc `Authorizcd Pcrsonncl nly Plcasc sign that markcd thc door
to thc cmcrgcncy dcpartmcnt, I wondcrcd who and what would bc
waiting fr mc. At thc nursing station, I askcd thc sccrctary whcrc thc
psychiatric nursc was. I had no sooncr askcd thc gucstion than Lisa
walkcd in. "I wcnt out and pcrsuadcd him to comc in. Thcy'rc in room
. Hc's not doing too wcll, I think hc'll nccd to bc admittcd. I'll call thc
unit and scc if wc havc any bcds'
"Has hc bccn hcrc bcfrc Wcrc you ablc to gct a chart I askcd.
"Thc last timc hc was hcrc was about tcn ycars ago, so hc only has
a papcr chart and it's in oh-sitc storagc. Wc might gct it in (8 hours,
but . . ' Shc turncd thc computcr scrccn so I could scc it. " Thc com-
putcr says hc was admittcd to thc mood disordcrs unit fr II days and
thc dischargc diagnosis was bipolar disordcr, manic cpisodc'
"Wcll, that's somc hclp. Lct's go scc thcm'
As soon as I opcncd thc door to thc intcrvicw room, I could scc
that [as usual) Lisa had sizcd up thc situation prctty accuratcly. Mr. and
Mrs . Wintcrs lookcd to bc in thcir carly hhics. Hc was sitting in a cor-
ncr, staring at thc floor, and hc lookcd as if hc hadn`t shavcd in about a
wcck. Mrs. Wintcrs was sitting ncxt to him but got up as I cntcrcd thc
room. "I practically had to carry him to gct him into thc car to comc
hcrc,' shc said. "I'vc bccn dcspcratc. Hc hasn't catcn anything in fur
days. Wc'vc only bccn marricd fr a ycar, and I didn`t rcalizc-I mcan,
I didn`t know how bad . . . I callcd his psychiatrist's omcc, but thcy said
shc wasn`t practicing anymorc'
2j2 M L1iL V i1 SY1iL 11
It took a whilc to gct Mrs. Wintcrs calmcd down, and cvcn longcr
to gct thc wholc story. Mr. Wintcrs was obviously in thc grip of scrious
dcprcssion and was barcly ablc to talk, lct alonc givc any kind of his-
tory of his problcms.
Mrs . Wintcrs showcd mc an cmpty bottlc of lithium capsulcs with
a "hllcd datc thrcc months old and
clcarly indicatcd. I
rccognizcd thc namc of thc prcscribing psychiatrist as a collcaguc who
had rctircd about six months bcfrc. I kncw fr a fct that shc had scnt
lcttcrs announcing hcr rctircmcnt almost a ycar bcfrc shc guit hcr
practicc group.
I was gctting thc morc rcccnt history hom Stan's wifc whcn I hcard
a knock on thc door. Lisa pcckcd in. "Or. Mondimorc, can I scc you fr
a momcnt
"Lxcusc mc,' I said and stcppcd outsidc. Lisa was holding thc
"prcfcrrcd-providcr and HM list that was postcd on thc LR bullctin
board. "His insurancc docsn`t pay hcrc. If hc nccds to bc admittcd, hc'll
havc to go to Harris Mcmorial'
"Crcat,' I grumblcd. "Hc dchnitcly nccds to bc in thc hospital, but
his wifc had a tcrriblc timc gctting him hcrc. I don`t think wc should
lct hcr transport him. Can you havc thc sccrctary call thc hospital
transportation pcoplc
Lisa howncd. "ur transportation won`t takc paticnts to a hospital
outsidc our systcm. Wc'll nccd to call an ambulancc'
"That will cost thcsc flks scvcral hundrcd dollars. Wc can't usc
our pcoplc fr a thrcc-milc ridc Lisa gavc mc hcr vcry bcst "I don`t
makc thc rulcs, I just fllow thcm look and said nothing. I took a dccp
brcath and prcparcd to go tcll thc Wintcrscs that it would probably bc
scvcral morc hours bcfrc Stan would bc i n thc hospital.

Mr. Wintcrs appcarcd to bc opcrating undcr thc assumption that his bipolar
disordcr had gonc away fr good [mistakc numbcr i). So whcn thc lcttcr
camc hom thc omcc of his psychiatrist announcing hcr rctircmcnt, hc put
oh making arrangcmcnts to gct hookcd up with a ncw onc [mistakc numbcr
z) . Whcn thc cmcrgcncy camc along, hc had no trcating physician fmiliar
with his situation. Hc and his wifc had obviously not had a vcry dctailcd dis-
cussion about bipolar disordcr, about what shc should do if symptoms flarcd
up lcaving Stan unablc to makc good dccisions about trcatmcnt [mistakc
numbcr ) . Mrs. Wintcrs was not fmiliar with thc law and thc proccdurcs in
thcir community rcgarding involuntary commitmcnt of pcrsons with psy-
chiatric illncss [mistakc numbcr () . And last but not lcast, thc Wintcrscs
wcrc unfmiliar with thc rcguircmcnts of thcir mcdical insurancc plan and
P1ii1iL 1LV AVLiL1S M 2jj
wcnt to a hospital whcrc thcir insurancc would not approvc hospitalization
[mistakc numbcr y ) .
How long would i t havc takcn t o prcvcnt all thcsc mistakcs An hour
or two Maybc thrcc bviously this would havc bccn timc wcll spcnt. Lct's
rcvicw somc of thc things it is important to know about in planning fr this
typc of cmcrgcncy.
Know Whom to CaII mr HcIp
I'vc always thought that thc pcoplc who can handlc almost anything arc
thosc who know whcn thcy nccd hclp and whom to call fr it. Pcrsons with
bipolar disordcr owc it to thcmsclvcs to bc undcr thc carc of a psychiatrist
who is fmiliar with thcir symptoms and thc coursc of thcir illncss. That
mcans cstablishing yoursclf with a ncw physician whcn you movc to a ncw
community or if any othcr fctor, such as thc rctircmcnt of your psychia-
trist, lcavcs you "uncovcrcd' Changcs in insurancc plans somctimcs frcc
a changc in psychiatrists. Oon't put oh making an appointmcnt to gct cs-
tablishcd as a paticnt in a ncw community or with a ncw practicc. 5ccausc
administrativc hasslcs and dclays can prolong thc timc it takcs fr rccords to
bc transfcrrcd hom onc omcc to anothcr, ask your providcrs if you can bc
givcn a copy of your rccords or a lcttcr of introduction that you can takc to
your ncw doctor at thc hrst appointmcnt.
Oon`t hcsitatc to ask thc psychiatrist how hcr practicc is covcrcd ahcr
hours. And how casy is it to gct a routinc omcc appointmcnt Arc somc ap-
pointmcnt slots sct asidc so that urgcnt appointmcnts can bc sct up within
a day or two Lvcry psychiatrist or mcntal-hcalth clinic should havc somc
mcans of sccing paticnts within twcnty-fur hours in cascs of truc cmcr-
gcncy. nc that docs not is onc to stccr clcar of.
5c surc you know how to contact thc psychiatrist or his omcc at any
timc of thc day or night and what arrangcmcnts arc in placc to handlc cmcr-
gcncics. Oocs thc psychiatrist scc his own cmcrgcncics, or docs cvcryonc in
thc practicc takc cmcrgcncy "on- call duty on a rotating basis Thc on- call
systcm, though not idcal, is ohcn thc standard in a practicc, it mcans that
you may wcll scc a doctor othcr than your rcgular onc if you havc an acutc
cmcrgcncy. Arc you prcparcd fr such an arrangcmcnt in ordcr to bc undcr
thc carc of a psychiatrist who comcs highly rccommcndcd
What hospitals docs your psychiatrist or hcr practicc havc a rclationship
with Oocs shc admit to thc hospital you prcfcr To thc hospital whcrc your
insurancc covcrs inpaticnt psychiatric trcatmcnt
If thc answcrs to thcsc gucstions arc not satisfctory, considcr your op-
tions. Ask your fmily doctor, fmily mcmbcrs, hicnds, or mcmbcrs of your
support group fr rccommcndations. Call thc local chaptcr of thc ational
2jq M L1iL V i1 SY1iL 11
Mcntal Hcalth Association, thc Ocprcssion and 5ipolar Support Alliancc, or
somc othcr advocacy group fr a rcfcrral. [Thcsc groups arc listcd in "Rc-
sourccs at thc cnd of this book. ) Somctimcs your options arc limitcd by
mcdical insurancc covcragc-which brings us to anothcr important aspcct
of bcing prcparcd.
Insurancc Issucs
5c fmiliar with thc dctails of your mcdical insurancc covcragc fr psy-
chiatric illncss . Although thc situation is changing, many plans trcat psychi-
atric illncsscs dihcrcntly hom nonpsychiatric illncsscs. Ior cxamplc, thcy
may havc dihcrcnt and strictcr limits on hospitalization covcragc, thc num-
bcr of outpaticnt visits thcy will pay fr, and thc pcrccntagc or amounts that
paticnts must pay out of pockct [ copaymcnts) fr ccrtain scrviccs. Oo you
havc a lifctimc "cap on psychiatric scrviccs This might bc a limit on days of
hospitalization or on thc numbcr of outpaticnt visits pcr ycar, or thcrc might
bc a dollar- amount limit to covcragc. Arc you limitcd to ccrtain hospitals or
practicc groups or covcrcd at a lowcr ratc if you don`t go to ccrtain hospitals
or psychiatrists If your insurancc company dcnics covcragc fr a hospi-
talization or fr scvcral days of hospitalization, what arc thc proccdurcs by
which you can appcal thc dccision
Hospital stays of all typcs havc bccomc shortcr, and psychiatric hospi-
talization is no cxccption. Hospitalization is now rcscrvcd almost cxclusivcly
fr lifc- thrcatcning cmcrgcncics, and paticnts arc dischargcd as soon as pos-
siblc. Paticnts arc no longcr hospitalizcd in a psychiatric unit or a psychiatric
hospital fr wccks or months. Oocs your psychiatrist havc acccss to a ar||a|
bcs| |a||ca||cnprogram [somctimcs also rcfcrrcd to as a daybcs| |a| )This
altcrnativc to traditional hospital trcatmcnt providcs hospital- likc monitor-
ing and trcatmcnt during thc day, or somctimcs fr only part of thc day, but
allows paticnts to rcturn homc in thc cvcning and spcnd thc night thcrc.
It is a vcry uscml trcatmcnt option fr bipolar disordcr bccausc it ohcrs a
way to providc daily monitoring of mood symptoms and trcatmcnt rcsponsc
without thc disruption to pcrsonal and fmily lifc that staying in a hospital
causcs. Somc insurcrs covcr a partial hospitalization-cvcn insist on it-but
othcrs do not. Know whcrc your insurancc company and your psychiatrist
stand on partial hospitalization.
carly all insurcrs havc somc frm of u||||ca||cn rcv|cwfr thcir poli-
cyholdcrs. Most contract this rolc to a manaycd carccryan|ca||cn [MC)
that supcrviscs or managcs how much mcdical carc you rcccivc. Thc utili-
zation rcvicw is accomplishcd in a varicty of ways, somc of which may bc
visiblc t o you, somc not. Thc main purposc is t o minimizc your usc of thc
morc cxpcnsivc typcs of mcdical carc, usually mcaning hospitalization and
P1ii1iL 1LV AVLiL1S M 2jj
trcatmcnt by spccialists. In an HM you may havc to bc rcfcrrcd by a pri-
mary physician to any spccialists-including psychiatrists-in ordcr to bc
covcrcd. Lab tcsts may bc covcrcd only i f your primary physician approvcs
thcm [this can makc it inconvcnicnt to gct thc blood tcsts nccdcd to monitor
thcrapy with lithium and somc othcr psychiatric drugs) . If you arc admittcd
to a hospital, your doctor is likcly bc callcd cvcry fcw days by somconc hom
thc MC asking why you still nccd to bc in thc hospital. If thc rcvicwcr
[usually a nursc) thinks you should bc dischargcd, hc will tcll your doctor
[and you) that covcragc will bc dcnicd ahcr a ccrtain datc and that you will
bc hnancially rcsponsiblc fr any additional inpaticnt trcatmcnt. [A varicty
of appcals proccdurcs usually kick in at this point if your doctor disagrccs. )
Managcd carc, which was oncc usually limitcd to inpaticnt trcatmcnt, is now
applicd to outpaticnt trcatmcnt as wcll, and psychiatrists arc bcing askcd to
hll out frms spccifying a trcatmcnt plan and rcgucsting a ccrtain numbcr
of omcc visits.
If thc insurancc plan includcs covcragc fr pharmacy chargcs, you may
not havc a choicc of brands of mcdication but will nccd to takc a gcncric
cguivalcnt instcad of thc cxact mcdication your psychiatrist prcscribcs.
Somc plans covcr only ccrtain drugs in a broadly dchncd class of mcdica-
tions, thus limiting thc doctor's prcscribing options. Your insurancc com-
pany may allow you to rcccivc only thirty days of mcdication at a timc, or
may imposc such a limit unlcss you usc a mail- ordcr pharmacy. Your doctor
may nccd to justify prcscriptions and ask pcrmission to prcscribc a highcr
dosc of a mcdication than usual, or to usc a mcdication "oh- labcl to trcat
you. Taking your prcscription to thc pharmacy is ohcn only thc hrst stcp in
gctting your mcdication, if a "prc- authorization`' is nccdcd, thcrc will bc a
scrics of phonc calls and fxcs back and frth bctwccn pharmacy, doctor's
omcc, and bcnchts managcr, a proccss that ohcn takcs scvcral days. If somc
sort of appcals proccss is ncccssary, it can takc wccks. All of this mcans that
you should scrupulously avoid waiting until thc last minutc to call fr a rchll.
Lvcn thcn, somc mcdications simply will not bc covcrcd undcr any cir-
cumstanccs. I oncc wrotc a lcttcr to a pharmacy bcnchts managcr fr pcr-
mission to prcscribc a mcdication "oh- labcl to trcat a paticnt. I includcd
a dozcn or so rcscarch rcfcrcnccs supporting thc rcgucst. Wc wcrc dcnicd
bccausc thcrc had bccn no "largc placcbo- controllcd clinical trial tcsting
thc particular situation that this paticnt was in. This was an impossibly high
standard to sct. if a particular clinical situation docsn`t arisc vcry ohcn, no
onc will invcst in a multimillion-dollar clinical trial to tcst that situation.
Managcd- carc mcthods savc millions upon millions of hcalth-carc dol-
lars. Somc pcoplc arguc that as a rcsult morc pcoplc havc acccss to bcttcr
mcdical carc bccausc thc systcm is morc cmcicnt and chcctivc. thcrs arguc
that "managcd carc is an oxymoron. 5ut thc fct is that managcd- carc
2 M L1iL V i1 SY1iL 11
mcthods arc uscd in all typcs of insurancc covcragc now. Your typc of mcd-
ical insurancc will almost ccrtainly dctcrminc which hospital you can bc ad-
mittcd to, and it may dctcrminc which doctor you can scc. Your insurancc
company will probably supcrvisc thc lcngth of your hospitalizations and
possibly control thc numbcr of omcc visits you can havc, which mcdications
can bc prcscribcd fr you, and likcly what doscs can bc prcscribcd. Thcrc-
frc, you should closcly scrutinizc all aspccts of your insurancc covcragc fr
psychiatric illncss, your cxisting policy and any ncw policics that you may
havc to choosc hom bccausc of job changcs. Oon`t bc bcguilcd by thc smil-
ing fccs on glossy brochurcs hom insurancc companics whcn it comcs to
picking a plan. Ask collcagucs and co-workcrs and pcrsons in your support
group about thcir cxpcricnccs with dihcrcnt plans and companics. Oon't put
yoursclf in thc position of gctting an cmcrgcncy-room surprisc.
Sahty Issucs and HosptaIzaton
Thc most dangcrous cmcrgcncy situation fr pcrsons with bipolar dis-
ordcr, and onc that hcgucntly lcads to hospitalization, is thc dcvclopmcnt of
suicidal thoughts and bchaviors. In studics hom thc I(os, suicidc ratcs of
o and cvcn 6o pcrccnt wcrc rcportcd in groups of bipolar paticnts. Thank-
mlly, thc availability of modcrn trcatmcnts fr bipolar disordcr has grcatly
changcd thcsc grim numbcrs. cvcrthclcss, thc ratc of suicidc dcaths in pcr-
sons with bipolar disordcr has bccn cstimatcd to bc at lcast Iy timcs highcr
than that sccn in thc gcncral population. ' It may sccm obvious to say that
thc most chcctivc way of minimizing thc risk of suicidc in bipolar disordcr
is rclapsc prcvcntion. 5ut if I had said "rc|ascprcvcntion is su|c|dcprcvcn-
tion`' in thc prcvious chaptcr, you might havc thought I was just bcing dra-
matic. Oo not cvcrlosc sight of thc fct that bipolar disordcr is a potcntially
ftal discasc. rclapsc prcvcntion |ssuicidc prcvcntion.
Individuals with bipolar disordcr should not havc hrcarms in thc homc.
Thcrc arc numcrous scicntihc studics showing that having a hrcarm in a
homc incrcascs thc chanccs of a violcnt dcath occurring in that homc, ci-
thcr by suicidc or by homicidc.' Whcrc an illncss whosc symptoms can in-
cludc suicidal dcprcssion and hcightcncd irritability with loss of inhibitions
is conccrncd, thcrc is ncvcr, cvcr any justihcation whatsocvcr fr having a
hrcarm of any typc in thc homc. Pcriod.
Thc cmcrgcncc of sclf- dcstructivc thoughts and impulscs is hightcn-
ing both to thc paticnt and to thosc around hcr. Thc trcmcndous stigma
and disgracc that havc bccn associatcd with suicidc fr ccnturics still makc
pcoplc rcluctant to discuss thcsc thoughts whcn thcy occur. That contcxt
and notions such as "only crazy pcoplc kill thcmsclvcs complicatc what is
rcally a much simplcr clinical issuc. suicidal thinking is a scrious symptom
P1ii1iL 1LV AVLiL1S M 2j,
of this illncss, which must bc cvaluatcd guickly by a profcssional and man-
agcd swihly and chcctivcly. Paticnts can bc intcnscly ashamcd of suicidal
thoughts and fccl that thc dcvclopmcnt of sclf- dcstructivc impulscs is a kind
of filurc. f coursc it is not a filing in any way, it is a symptom of an illncss.
It is important to undcrstand thc dcvclopmcnt of suicidal fcclings in a bipo-
lar paticnt as a vcry dangcrous symptom of scrious illncss, as dangcrous as
thc onsct of chcst pains i n a hcart paticnt. Whcn thcy occur, it's not a timc to
wondcr about what thcy mcan. I|:||mc|c ca||}crbc|.And likc chcst pains
in a hcart paticnt, suicidal fcclings in a mood- disordcr paticnt arc ohcn a
rcason fr hospitalization.
Psychiatric hospitalization can bc cxpcricnccd as a tcrriblc filurc. Again,
thc clinical pcrspcctivc tclls us othcrwisc. Although wc havc bccomc much
bcttcr at trcating bipolar disordcr, our trcatmcnt mcthods arc by no mcans
pcrfcct. Somctimcs, dcspitc cvcryonc's bcst chorts, rclapscs occur and sc-
rious symptoms likc suicidal fcclings cmcrgc and rcguirc hospitalization.
Such an occurrcncc i s not timc fr sclf-blamc or gucstions likc, What did I
do wrong Rathcr, it's timc fr hcaling.
Rcmcmbcr that thc word wc ohcn uscd in thc past fr psychiatric hos-
pitals was asy|um, a tcrm dchncd as "a placc ohcring protcction and safcty''
Individuals whosc will has bccn tcmporarily scizcd by this tcrriblc illncss
and who arc on thc vcrgc of tcrriblc and dcspcratc action dcscrvc a placc
of protcction and safcty. o apologics arc cvcrncccssary, no rcproach cvcr
nc morc rcmindcr. bipolar disordcr can raisc issucs of pcrsonal safcty.
Thcsc issucs nccd to bc anticipatcd, discusscd, planncd fr, and promptly
addrcsscd if and whcn thcy arisc. 5ccausc fmily mcmbcrs arc ohcn a cru-
cial part of dcaling with thcsc cmcrgcncics, I'll discuss thcir rolc mrthcr in
thc ncxt chaptcr.
2 M L1iL V i1 SY1iL 11
DO HO1O O1 1DO IdH11j
L M A 1 H 2
limitcd to thosc who havc thc discasc. Iamily and hicnds fcc thc challcngcs
as wcll. It's intcnscly painml to scc a lovcd onc suhcr hom thc dcspcratc
blcakncss of major dcprcssion, and just as painml and hightcning to scc him
in thc hcnzicd grip of mania. As in any illncss, thc rolc of thc fmily includcs
support, undcrstanding, and cncouragcmcnt of thc pcrson who is ill. Thc
hrst stcp in bcing ablc to providc this kind of support is undcrstanding somc
vcry important fcts about thc illncss .
Rccognzng Symptoms
cvcr frgct that thc pcrson with bipolar disordcr docs not havc control
of hcr mood statc. Thosc of us who do not suhcr hom a mood disordcr
somctimcs cxpcct mood- disordcr paticnts to bc ablc to cxcrt thc samc con-
trol ovcr thcir cmotions and bchavior that wc oursclvcs arc ablc to. Whcn wc
scnsc that wc arc lctting our cmotions gct thc bcttcr of us and want to sub-
duc thcm, wc tcll oursclvcs things likc "Snap out of it,' "Cct hold of yoursclf,'
"Try and pull yoursclf out of it' Wc arc taught that sclf-control is a sign of
maturity and sclf- disciplinc. Wc arc indoctrinatcd to think of pcoplc who
don`t control thcir cmotions vcry wcll as bcing immaturc, lazy, sclf- indulgcnt,
or folish. 5ut you can only cxcrt sclf-control if thc control mcchanisms arc
working propcrly, and in pcoplc with mood disordcrs, thcy arc not.
Pcoplc with mood disordcrs cannot "snap out of it,' much as thcy would
likc to [and it's important to rcmcmbcr that thcy want dcscra|c|yto bc ablc
to) . Tclling a dcprcsscd pcrson things likc "Pull yoursclf out of it is crucl
and may rcinfrcc thc fcclings of worthlcssncss, guilt, and filurc alrcady
prcscnt as symptoms of thc illncss. Tclling a manic pcrson, "Slow down and
gct hold of yoursclf is simply wishml thinking, that pcrson is likc a tractor
trailcr carccning down a mountain highway with no brakcs.
So thc hrst challcngc fcing fmily and hicnds is to changc thc way thcy
look at bchaviors that might bc symptoms of thc illncss-bchaviors likc not
wanting to gct out of bcd, bcing irritablc and short-tcmpcrcd, bcing "hypcr
and rccklcss or ovcrly critical and pcssimistic. ur hrst rcaction to thcsc
sorts of bchaviors and attitudcs is to rcgard thcm as lazincss, mcanncss, or
immaturity and to bc critical of thcm. In a pcrson with bipolar disordcr,
criticism almost always makcs things worsc. it rcinfrccs thc dcprcsscd pa-
ticnt's fcclings of worthlcssncss and filurc, and it alicnatcs and angcrs thc
hypomanic or manic paticnt.
This is a hard lcsson to lcarn. Oon`t always takc bchaviors and statcmcnts
at fcc valuc. Lcarn to ask yoursclf, "Could this bc a symptom bcfrc you
rcact. Littlc childrcn hcgucntly say "I hatc you whcn thcy arc angry at thcir
parcnts, but good parcnts know that it's just thc angcr of thc momcnt talking,
this is not thc child's truc fccling. Manic paticnts will say "I hatc you too, and
it's thc illncss talking, an illncss that has hij ackcd thc paticnt's cmotions. Thc
dcprcsscd paticnt will say, "It's hopclcss, I don't want your hclp' Again, it's
thc illncss and not your lovcd onc rcj ccting your conccrn.
I'm now going to makc things rcally dimcult by warning against thc
othcr cxtrcmc. intcrprcting cvcrystrong cmotion in a pcrson with a mood
disordcr as a symptom. This othcr cxtrcmc i s just as important to guard
against. I havc sccn many couplcs in which onc partncr has a bipolar disor-
dcr and thc hcalthy partncr wiclds thc diagnosis as a wcapon to cmotionally
subduc thc othcr. [Comc to think of it, that docsn't sound vcry "hcalthy,'
docs it)

"Vic|'s mcdication nccds an adjustmcnt. I'm surc of it'
Vicky starcd down at thc floor angrily as Pctcr wcnt on. "Shc won`t
givc up on this crazy idca about going back to collcgc' I winccd a littlc
at Pctcr's usc of thc word cracy, a word that can makc a pcrson with a
psychiatric illncss fccl likc thcy'vc just bccn slappcd in thc fcc. I madc
a mcntal notc to bring it to his attcntion latcr, but to do so now might
makc it look as if I was "taking sidcs'
"Pctcr,' I said, `` likc to hcar hom Vic| about this. Shc's bccn
2q0 M L1iL V i1SY1iL 11
doing wcll fr ovcr two ycars now, I think it may bc timc to havc a
scrious discussion about hcr idca'
Vic| lookcd up. "I was six months away hom graduating hom
5ryn Mawr whcn I got sick thc hrst timc. I'vc callcd Statc, St. [amcs
Collcgc, and Lvcrctt, and I could gct my dcgrcc with only a ycar of
study at any of thcm'
Vic| was in hcr mid-thirtics, an intcnsc, vibrant woman who I
suspcctcd was probably brilliant as wcll. Pctcr had bccn transfcrrcd
to town by his company a month ahcr Vicky had gottcn out of thc
hospital fllowing a ncarly lcthal suicidc attcmpt. It had takcn thrcc
hospitalizations fr hcr to bc propcrly diagnoscd as having bipolar
disordcr-ahcr ncarly tcn ycars of rollcr- coastcr moods . Shc had bccn
trcatcd fr a dcprcssivc disordcr, fr a pcrsonality disordcr, cvcn fr
schizophrcnia bcfrc shc startcd on valproatc and had a big turn-
around. Shc had donc so wcll, in fct, that I had sccn hcr only half a
dozcn timcs ovcr thc past two ycars. About half thc timc hcr husband
camc along to hcr appointmcnts. Lvcry couplc of months I noticcd a
book rcvicw shc had writtcn in thc local ncwspapcr, and on onc visit
shc had mcntioncd working on a biography of Mary Todd Lincoln.
Coing back to collcgc sccmcd wcll within hcr capabilitics.
Pctcr sighcd, thcn wcnt on. "It makcs mc rcally ncrvous to scc
hcr up latc at night looking at collcgc cntrancc rcguircmcnts ovcr thc
Intcrnct. And wc'vc gottcn dozcns of collcgc catalogs through thc mail
that shc's callcd or writtcn fr. I'm ahaid shc's gctting manic, and I just
can`t go through that again'
Vic|'s cycs flashcd, and shc drcw in hcr brcath, thcn slowly
rclcascd it. "Pctcr's not uscd to mc bcing this conhdcnt and cncrgizcd
about anything. Wc'vc only bccn marricd fr fur ycars, and fr ncarly
two of thosc I was morc or lcss dcprcsscd. This is mc, not mania' Hcr
voicc bccamc just thc slightcst bit loudcr. "5ut hc's trcating mc likc a
child, an incompctcnt' Shc lookcd ovcr at hcr husband. "A lunatic,
right I'm hnally gctting back to m} goals and carccr ahcr tcn ycars,
and what did you call it `Crazy'
ow i t was Pctcr's turn to look angry. "You scc, Ooctor Oo you
scc what I mcan, how angry shc gcts Shc's not usually likc this. 5cfrc
wc camc hcrc today, shc-
"h, Cod, stop it' Vic| said guictly, through clcnchcd tccth.
Tcars wcrc flowing now.
"K, you two, lct's cool down fr a momcnt,' I said. I could scnsc
that this was a continuation of a powcr strugglc bctwccn Pctcr and
Vic| that had probably bccn going on fr wccks, maybc cvcn months.
H VL1 L1 H 1A11Y M 2q1
5ut I also had thc scnsc that Vicky was asscssing hcrsclf accuratcly and
that Pctcr was ovcrrcacting. Vicky was not bcing carricd away by hcr
fcclings-not at thc momcnt, at lcast, if anything, shc was showing a
lot of rcstraint. Pctcr wastrcating hcr likc a child.
"Vicky,' I said, "pcrhaps Pctcr docsn`t undcrstand your rcasons fr
wanting to go back to collcgc'
"I admit it might sccm likc a wastc of timc,' shc said. "5ut that
dcgrcc mcans a lot to mc. I was dcvastatcd whcn I had to withdraw
hom collcgc. I fclt likc a complctc filurc. Maybc I just nccd to provc
to mysclf that I can do it. That I'm not . . ' Shc hcsitatcd bcfrc spitting
it out. "ot crazy'
Pctcr was calmcr, too. "It's not that wc can`t ahord it,' hc said. "I
just worry that it will bc too much fr hcr, that shc'll gct sick again.
And shc gcts so angry whcn wc talk about it, shc sccms obscsscd with
this idca. That's not normal, is it
"I don't think trying to dccidc how much obscssivcncss is normal
or abnormal is going to hclp us hcrc, Pctcr,' I said. "It sccms to mc
that thc problcm is that Vicky is invcsting a lot of timc and cmotional
cncrgy in a proj cct that you don't think is worthwhilc'
"That's right,' Pctcr said dccisivcly.
"5ut Ithink it's worthwhilc,' Vic| said. "[ust bccausc I havc a
psychiatric illncss docsn`t invalidatc mc as a pcrson. It docsn`t mcan I
nccd somconc to makc all my dccisions fr mc'
"Honcy, I'm just trying to hclp you, to protcct you-
Vic| snappcd back, "I don`t want to bc protcctcd, I want to havc a
rcal lifc'
"Wait a minutc, wait a minutc,' I said. "I think wc wcrc gctting
somcwhcrc. Lct's go back to Vic|'s rcasons fr wanting to go back to

This strugglc bctwccn Pctcr and Vicky illustratcs a vcry common prob-
l cm that can comc up i n fmilics i n which an individual has bccn diagnoscd
with a bipolar illncss. It's possiblc to jump to thc conclusion that cvcrything
thc ill pcrson docs that might bc folish or risky is a symptom of illncss,
cvcn to thc point of hauling thc pcrson in to thc psychiatrist's omcc fr a
"mcdication adjustmcnt cvcry timc hc disagrccs with spousc, partncr, or
parcnts. As with Pctcr and Vic|, a vicious cyclc can takc ovcr . somc bold
idca or cnthusiasm, or cvcn plain old folishncss or stubbornncss, is labclcd
as "gctting manic,' and fcclings of angcr and rcscntmcnt arc stirrcd up in thc
pcrson with thc diagnosis. Whcn thcsc angry fcclings arc cxprcsscd, thcy
sccm to conhrm thc fmily's suspicion that thc pcrson is "gctting sick again,'
2q2 M L1iL V i1SY1iL 11
so morc criticism cnsucs, fllowcd by morc angcr, and so on. "Hc's gctting
sick again`' somctimcs bccomcs a sclf-mlhlling prophccy. so much angcr and
cmotional strcss arc gcncratcd that a rclapsc dccsoccur, bccausc thc pcrson
with thc illncss stops taking thc mcdication that controls his symptoms, out
of hustration and angcr and shamc. "Why bothcr staying wcll, if I'm a|ways
trcatcd as if I wcrc sick
So how docs onc walk this hnc linc bctwccn not taking cvcry fccling
and bchavior at fcc valuc in a pcrson with bipolar disordcr, on thc onc
hand, and not invalidating "rcal fcclings by calling thcm symptoms, on thc
othcr I think communication is thc kcy. honcst and opcn communication.
Ask thc pcrson with thc illncss about hcr moods, makc obscrvations about
bchaviors, cxprcss conccrns in a caring, supportivc way. Co along with your
fmily mcmbcr to doctors' appointmcnts, and sharc your obscrvations and
conccrns during thc visit in thc fmily mcmbcr's prcscncc. Abovc all, do not
call thc thcrapist or psychiatrist and say, "I don`t want my husband,
wifc, son, daughtcr , hll in thc blank] to know that I callcd you, but I think it's
important to tcll you that . . ' Thcrc's nothing morc inmriating or dcmcan-
ing than to havc somconc rcporting on you bchind your back.
5ut it's also possiblc to crr on thc sidc of not bcing involvcd cnough in
trcatmcnt fr fcar of bcing a "tattlctalc,' assuming that thc clinicians will
noticc thc samc things you'vc noticcd about changcs in moods or bchaviors.
nc of thc most valuablc ways a fmily mcmbcr can hclp is to providc a
clcar, undistortcd vicw of thc situation to thc clinical tcam trcating thc ill-
ncss. In my cxpcricncc, fmily mcmbcrs arc hcgucntly thc hrst to pick up on
subtlc changcs in bchaviors and attitudcs that signal thc bcginning of a rc-
lapsc. I don't know how many timcs I havc sccn paticnts in thc clinic or cvcn
in thc cmcrgcncy room who rcassurcd mc that thcy wcrc fccling hnc, thcir
bchavior and mood sccmcd normal, so I scnt thcm on thcir way with a notc
in thc chart that thcy wcrc doing wcll. Thcn I rcccivcd a panickcd phonc call
hom a spousc or othcr rclativc a fcw hours latcr. "Oidn`t hc tcll you that hc's
lost tcn pounds " . . . that shc hasn`t slcpt in thrcc nights " . . . that hc got
hrcd hom his j ob Contrary to popular bclicf, psychiatrists cannot rcad
minds| 5ccomc involvcd with trcatmcnt, and communicatc your conccrns
opcnly, sinccrcly, and supportivcly-almost anything that might othcrwisc
sccm intrusivc can bc frgivcn.
Rcmcmbcr that your goal i s to havc your fmily mcmbcr trust you whcn
shc fccls most vulncrablc and hagilc. Shc is alrcady dcaling with fcclings
of dccp shamc, filurc, and loss of control rclatcd to having a psychiatric
illncss. 5c supportivc, and ycs, bc constructivcly critical whcn criticism is
warrantcd. 5ut abovc all, bc opcn, honcst, and sinccrc.
H VL1 L1 H 1A11Y M 2qj
InvoIuntary Trcatmcnt and Omcr LcgaI Issucs
In cvcry community thcrc arc laws and proccdurcs to safcguard individ-
uals who arc unablc to carc fr thcmsclvcs. Laws that allow thc rcmoval of
childrcn hom thc carc of parcnts who arc abusing thcm arc thc most obvious
cxamplc. Anothcr sct of laws allow individuals to bc trcatcd fr psychiatric
illncsscs against thcir will in ccrtain circumstanccs. nc of thc most dimcult
things a pcrson might bc callcd on to do fr a fmily mcmbcr with bipolar
disordcr is to initiatc involuntary trcatmcnt or commitmcnt. 5ut givcn thc
powcr of this illncss [cspccially bipolar I) to cloud judgmcnt and crcatc dan-
gcrous situations, thcrc is somctimcs no choicc but to frcc thc trcatmcnt
issuc in this way. It is always a last rcsort, but it can litcrally bc lifcsaving.
Commitmcnt laws arc usually statc laws and so vary hom onc statc to
anothcr, in addition to thcsc statc-by- statc variations, local proccdurcs can
vary hom community to community. Thcrcfrc, I can`t providc a stcp-by-
stcp proccdurc hcrc, only gcncral principlcs. 5ut in my cxpcricncc, it's not
thc proccdurcs that conmsc pcoplc, it's thc gcncral principlcs, so I think a
bricf discussion will bc worthwhilc.
Laws and lcgal proccdurcs govcrning thc provision of psychiatric trcat-
mcnt-or any kind of mcdical trcatmcnt, fr that mattcr-against a pcr-
son`s statcd wishcs arc bascd on thc knowlcdgc that an individual whosc
judgmcnt i s cloudcd by thc symptoms of an illncss ohcn docs not makc
thc samc dccisions about trcatmcnt that hc would makc othcrwisc. Thc dc-
lirious motor-vchiclc-accidcnt victim who has suhcrcd massivc blood loss
may moan "I want to go homc as shc loscs consciousncss on thc strctchcr,
but thc LR tcam will ignorc such a statcmcnt and procccd to do what thcy
havc to do to savc thc pcrson`s lifc. It is prcsumcd that if thc pcrson wcrc
alcrt and thinking clcarly and undcrstood thc implications of "going homc,'
shc would not makc such a rcgucst. Similar principlcs undcrlic psychiatric
commitmcnt laws. trcatmcnt is givcn to pcrsons against thcir will if cloudcd
judgmcnt prcvcnts thcm hom making good dccisions about thcir trcatmcnt.
Ocprcsscd individuals may bc so hopclcss that thcy fccl trcatmcnt has no
chancc of hclping. Thinking proccsscs in mania can bc so disorganizcd and
scattcrcd that sccking out and coopcrating with trcatmcnt is not possiblc. In
cithcr casc thcrc arc mcchanisms to gct nccdcd trcatmcnt fr pcrsons whosc
psychiatric symptoms blind thcm to thc nccd fr it.
Iortunatcly, thcsc laws also havc safcguards built in to prcvcnt conhnc-
mcnt in a psychiatric hospital fr thc wrong rcasons. Occadcs ago it was vcry
casy to invokc commitmcnt law, and it ohcn rcguircd only thc signaturc of a
rclativc or fmily physician to hospitalizc a pcrson fr wccks or months, or
cvcn ycars. Pcoplc wcrc hospitalizcd fr all kinds of bogus rcasons, and scri-
ous abuscs of individual rights occurrcd. Laws bccamc much strictcr in thc
2qq M L1iL V i1SY1iL 11
I6os and I;os to prcvcnt such abuscs. Thc main changc was thc addition
of danycrcusncssas a commitmcnt critcrion. Lnlcss an individual's bchavior
cndangcrs himsclf-usually mcaning suicidal bchavior-or othcrs, thc pcr-
son cannot bc committcd fr involuntary psychiatric trcatmcnt.
Rcgucsts or pctitions fr involuntary commitmcnt do not ncccssarily
mcan that thc pcrson who is allcgcd to bc psychiatrically ill will bc hospi-
talizcd. Iricnds and rclativcs cannot admit a paticnt in to a hospital, only
a doctor can do so. Thc fmily's rcgucst fr involuntary commitmcnt usu-
ally will allow thc paticnt to bc transportcd to an cmcrgcncy room, whcrc
a physician will makc a dccision about hospitalization. Thc paticnt may bc
rclcascd i f shc docs not mcct lcgal critcria fr commitmcnt.
Involuntary commitmcnt is a lcgal proccdurc in which an individual is
conhncd against his will and tcmporarily loscs somc rights of sclf-dctcrmi-
nation. Ior this rcason thc law and thc courts takc involuntary psychiatric
trcatmcnt vcry scriously, and many safcguards against abuscs arc built in to
thc proccdurcs. Thc pcrson rcgucsting thc involuntary commitmcnt must
usually appcar in pcrson at thc local courthousc or policc station to givc
infrmation and, in somc jurisdictions, makc a sworn statcmcnt bcfrc a
judgc or magistratc. Iamily or hicnds will bc askcd fr vcry spccihc and
dctailcd infrmation about thc bchaviors thcy havc obscrvcd. This is ohcn
hustrating fr thosc trying to gct hclp fr thcir lovcd onc. Thcy may fccl
that it's uncaring fr thcm to bc askcd such a lot of gucstions or that thcir
judgmcnt or motivcs arc bcing gucstioncd. It's important to rcmcmbcr that
in thc days whcn individuals could bc conhncd to psychiatric hospitals sim-
ply bccausc a rclativc or doctor "thought it was bcst fr thcm, thcrc wcrc
signihcant abuscs of civil rights. Whcn thcrc is scrious attcntion on thc part
of thc issuing magistratc or judgc to documcnting thc fcts and gucstioning
thc nccd fr involuntary trcatmcnt, it mcans that thc systcm is working.
Thcrc is a judicial rcvicw [a "commitmcnt hcaring) at somc point [ usu-
ally a fcw days ahcr admission to a hospital), whcrcin a judgc or hcaring
omccr dctcrmincs that thc commitmcnt proccdurc was donc propcrly and
lcgally. Although this is a lcgal procccding, it is not a big courtroom sccnc.
Lsually a confcrcncc room in thc hospital is uscd, only a fcw pcoplc arc prcs-
cnt, and thc procccdings arc kcpt conhdcntial [thcy arc not a mattcr of pub-
l i c rccord) . Thc paticnt i s allowcd lcgal rcprcscntation, i n fct an attorncy
will bc appointcd to rcprcscnt thc paticnt if shc cannot ahord to hirc onc.
Involuntary commitmcnt fr psychiatric trcatmcnt docs not usually af-
fcct a pcrson's othcr lcgal rights. Wills or othcr lcgal instrumcnts hc has cxc-
cutcd arc not invalidatcd, and paticnts do not bccomc lcgally "incompctcnt
in othcr arcas. Hospitalization and trcatmcnt arc thc only issucs that arc
addrcsscd in commitmcnt hcarings.
ccasionally individuals with scvcrc, poorly controllcd bipolar disor-
H VL1 L1 H 1A11Y M 2qj
dcr and thcir fmilics makc lcgal arrangcmcnts to safcguard thc individu-
als' hnancial asscts in casc anothcr scvcrc cpisodc of thc illncss comcs upon
thcm. This can involvc actually having a lcgally appointcd guardian who
might control acccss to bank accounts, prcvcnt thc salc of propcrty or othcr
asscts, and so frth. Although rarcly ncccssary, this is a valuablc option that
can go a long way toward prcvcnting hnancial ruin causcd by manic spcnd-
ing sprccs. A documcnt callcd a cwcrc}a||crncy can convcy ccrtain spc-
cihc rcsponsibilitics and powcrs-and not othcrs-and docs not constitutc
guardianship. Carcml considcration and consultation with an attorncy arc,
of coursc, ncccssary so that lcgally binding documcnts with safcguards ap-
propriatc to thc situation can bc drahcd.
I am awarc that thc topic of this scction of thc chaptcr is a vcry hight-
cning onc, cspccially to pcrsons with bipolar disordcr, to whom it might
sccm that libcrty and thc right of sclf- dctcrmination can bc takcn away all
too casily. At thc risk of sounding glib, howcvcr, I want to rcassurc you that
involuntary commitmcnt of an individual is nc|a guick and casy proccdurc.
n thc contrary, in my cxpcricncc most pcoplc arc surpriscd at how dimcult
it is to invokc thcsc laws, how many safcguards arc built in to thc proccdurcs,
and how scriously thc strict intcrprctation of thc laws is takcn by cvcryonc
involvcd. Thc laws covcring involuntary commitmcnt havc bccn carcmlly
writtcn in thc intcrcst of hclping, not simply conhning, pcoplc with scvcrc
psychiatric illncsscs. In my cxpcricncc thcy arc chcctivc at doing just that.
Morc on Sahty
cvcr frgct that bipolar disordcr can occasionally prccipitatc truly dan-
gcrous bchavior. Kay [amison writcs of thc "dark, hcrcc and damaging cn-
crgy of mania and thc cvcn darkcr spcctcr of suicidal violcncc that haunts
thosc with scrious dcprcssion. ' Violcncc is ohcn a dimcult subj cct to dcal
with bccausc thc idca is dccply cmbcddcd in us hom an carly agc that vio-
lcncc is primitivc and uncivilizcd and rcprcscnts a kind of filurc or brcak-
down in charactcr. f coursc wc rccognizc that thc pcrson in thc grip of
psychiatric illncss is not violcnt bccausc of somc pcrsonal filing, and pcr-
haps bccausc of this thcrc is somctimcs a hcsitation to admit thc nccd fr
a propcr rcsponsc to a situation that is gctting out of control. whcn thcrc is
somc thrcat of violcncc, toward cithcr sclf or othcrs.
I'vc alrcady talkcd a bit about suicidal thinking, and it bcars rcpcating
that pcoplc with bipolar disordcr arc at much highcr risk fr suicidal bc-
havior than thc gcncral population. Although fmily mcmbcrs cannot and
should not bc cxpcctcd to takc thc placc of psychiatric profcssionals in cval-
uating suicidc risk, it is important to havc somc fmiliarity with thc issuc.
Again, paticnts who arc starting to havc suicidal thoughts arc ohcn intcnscly
2q M L1iLV i1 SY1iL 11
ashamcd of thcm. Thcy will ohcn hint about "fccling dcspcratc,' about "not
bcing ablc to go on,' but thcy may not vcrbalizc actual sclf- dcstructivc
thoughts. It's important not to ignorc thcsc statcmcnts but rathcr to clari
thcm. Oon`t bc ahaid to ask, "Arc you having thoughts of hurting yoursclf
Pcoplc arc usually rclicvcd to bc ablc to talk about thcsc fcclings and gct
thcm out into thc opcn whcrc thcy can bc dcalt with. 5ut thcy may nccd
pcrmission and support to do so.
Rcmcmbcr that thc pcriod of rccovcry hom a dcprcssivc cpisodc can
bc a timc of cspccially high risk fr suicidal bchavior. Pcoplc who havc bccn
immobilizcd by dcprcssion somctimcs dcvclop a highcr risk fr hurting
thcmsclvcs as thcy bcgin to gct bcttcr and thcir cncrgy lcvcl and ability to act
improvc. Paticnts having mixcd symptoms-dcprcsscd mood and agitatcd,
rcstlcss, hypcractivc bchavior-may also bc at highcr risk fr sclf- harm. In
fct, thcrc is somc cvidcncc that mixcd or dysphoric mania is thc most dan-
gcrous mood statc in this rcgard. '
Anothcr fctor that incrcascs thc risk of suicidc is substancc abusc, cs-
pccially alcohol abusc. Alcohol not only worscns a pcrson`s mood, but it low-
crs inhibitions. Pcoplc will do things whcn thcy arc drunk that thcy wouldn`t
do othcrwisc. Incrcascd usc of alcohol incrcascs thc risk of suicidal bchav-
iors and is dchnitcly a worrisomc dcvclopmcnt that nccds to bc conhontcd
and actcd upon.
Thc dcvclopmcnt of scrious suicidal risk calls fr action. Havc an cmcr-
gcncy plan, and bc prcparcd to usc it. Oon't hcsitatc to invokc involuntary
commitmcnt proccdurcs if you arc rcally worricd and thc paticnt is disput-
ing thc nccd fr cvaluation.
A lcss hcgucnt but ncvcrthclcss vcry rcal risk of violcncc i s thc vio-
lcncc toward othcrs that can occur in mania. Iricnds and fmily mcmbcrs
should not hcsitatc to call fr policc hclp if thcy fccl thrcatcncd. "What will
thc ncighbors think should not bc an issuc whcrc safcty is conccrncd. If
thc situation is bccoming dangcrous, don`t call thc psychiatrist's omcc or thc
local cmcrgcncy room, dial II. Policc omccrs arc accustomcd to dcaling
with psychiatrically ill individuals. Thcy know safc physical rcstraint tcch-
nigucs, and thcy will bc fmiliar with psychiatric cmcrgcncy scrviccs in thc
community. Policc omccrs can bc cxpcctcd to havc thc samc goals you havc
in thc situation. transporting thc paticnt guickly and safcly to thc appropri-
atc hcalth-carc fcility so that shc can rcccivc propcr trcatmcnt.
Gcttng Support
It's important fr fmily mcmbcrs to rccognizc thcir own nccd fr sup-
port, cncouragcmcnt, and undcrstanding in dcaling with this illncss. Mcn-
tal-hcalth profcssionals go homc cvcry day and lcavc thcir work of dcaling
H VL1 L1 H 1A11Y M 2q,
with psychiatric illncsscs bchind, an option that fmily mcmbcrs ohcn do
not havc. It can bc cxhausting to livc with a hypomanic pcrson and hustrat-
ing to dcal with a scriously dcprcsscd pcrson day ahcr day. Thc changcs and
unprcdictability of thc moods of somconc with bipolar disordcr intrudc into
homc lifc and can bc thc sourcc of scvcrc strcss in rclationships, straining
thcm to thc brcaking point.
Pcrhaps thc most dimcult challcngc is that poscd by a fmily mcmbcr
with bipolar disordcr who is rcsistant to obtaining trcatmcnt. Thc most as-
tonishing lcarning cxpcricncc that mcdical studcnts and intcrns havc is with
thcir hrst paticnt who rcpcatcdly rcmscs to continuc with a trcatmcnt that
will kccp him wcll and out of thc hospital. I rcmcmbcr as a rcsidcnt rcading
thc chart of a bipolar paticnt who had bccn admittcd to thc hospital dozcns
of timcs ahcr stopping lithium. Why on carth, I wondcrcd, would a pcrson
makc such a folish dccision again and again I rcmcmbcr thinking that tak-
ing thrcc capsulcs of lithium a day sccmcd a vcry small inconvcnicncc com-
parcd with spcnding what addcd up to scvcral ycars of this paticnt's lifc in
a psychiatric hospital. I'vc sincc lcarncd that making pcacc with thc illncss
and with thc idca of staying in trcatmcnt is much morc dimcult than hcalthy
pcoplc rcalizc [scc chaptcr zo) . 5ut thc hardcr lcsson is that thcrc is no way
anyonc can }crcc a pcrson to takc rcsponsibility fr hcr trcatmcnt. Lnlcss
thc paticnt makcs thc commitmcnt to do so, no amount of lovc and support,
sympathy and undcrstanding, cajoling or cvcn thrcatcning can makc somc-
onc takc this stcp. Lvcn fmily mcmbcrs who undcrstand this at somc lcvcl
may fccl guilty, inadcguatc, and angry at timcs dcaling with this situation.
Thcsc arc vcry normal fcclings. Iamily mcmbcrs should not bc ashamcd of
thcsc fcclings of hustration and angcr but rathcr gct hclp with thcm.
Lvcn whcn thc paticnt docs takc rcsponsibility and is trying to stay wcll,
rclapscs can occur. Iamily mcmbcrs might thcn wondcr what |bcy did
wrong. Oid I put too much prcssurc on him Could I havc bccn morc sup-
portivc Why didn't I noticc thc symptoms coming on sooncr and gct hcr to
thc doctor A hundrcd gucstions, a thousand "if only's,' anothcr round of
guilt, hustration, and angcr.
n thc othcr sidc of this issuc is anothcr sct of gucstions. How much
undcrstanding and support fr thc bipolar pcrson might bc too much What
is protcctivc, and what is ovcrprotcctivc Should you call your lovcd onc's
boss with cxcuscs rcgarding why hc isn`t at work Should you pay oh crcdit
card dcbts hom hypomanic spcnding sprccs causcd by dropping out of
trcatmcnt What actions constitutc hclping a sick pcrson, and what actions
arc hclping a pcrson to bc sick Thcsc arc thorny, complcx gucstions that
havc no casy answcrs.
Ior all thcsc rcasons, it's vital that fmily mcmbcrs go along with thc
paticnt to support groups-and go to support groups thcmsclvcs cvcn if thc
2q M L1iL V i1SY1iL 11
paticnt will not go-and considcr gctting counscling or thcrapy fr thcm-
sclvcs to dcal with thc strcsscs causcd by this illncss. Comprchcnsivc pro-
grams fr thc trcatmcnt of pcrsons with bipolar disordcr arc incrcasingly
cmphasizing fmily involvcmcnt.
Likc many othcr chronic illncsscs, bipolar disordcr amicts onc but af-
fccts many in thc family. It's important that a||thosc ahcctcd gct thc hclp,
support, and cncouragcmcnt thcy nccd.
H VL1 L1 H 1A11Y M 2q
L M A 1 H 2 J
Thc diagnosis of bipolar disordcr and othcr psychiatric illncsscs is bccoming
morc accuratc all thc timc. Thc availablc trcatmcnts fr thcsc illncsscs arc
morc chcctivc, and thcrc arc morc of thcm. 5ut thcsc advanccs havc comc
about largcly through trial and crror, not through a bcttcr scicntihc undcr-
standing of thc causcs of thc discascs. Thc situation is changing, howcvcr.
Thousands of scicntists in two dihcrcnt disciplincs arc conducting rcscarch
that will cvcntually lcad to a mllcr undcrstanding of psychiatric illncsscs and
to ncw and morc chcctivc trcatmcnt approachcs.
Thc hrst of thcsc is thc hcld of ncurcsc|cncc,thc study of thc biology and
chcmistry of thc brain and ncrvous systcm. At thc bcginning of thc twcnti-
cth ccntury, thc physical and psychiatric cxamination of paticnts with brain
disordcrs and thc microscopic study of brain tissuc obtaincd hom thcm
ahcr dcath wcrc thc only availablc mcthods to invcstigatc thc discascs of thc
brain. Animal cxpcrimcnts complcmcntcd thcsc studics, but this work rc-
sultcd in only thc vagucst outlinc of thc organization of brain mnction. Thc
location of brain arcas important fr spccch, movcmcnt, vision, and so frth
wcrc discovcrcd, but psychiatric illncsscs rcmaincd so mystcrious that idcas
having nothing to do with biology, thcorics such as psychoanalysis, wcrc thc
only oncs that sccmcd to ohcr any hopc of undcrstanding thcsc problcms.
5y thc cnd of thc ccntury, howcvcr, brcakthrough fllowcd upon brcak-
through, mostly in thc hcld of thc chcmistry of brain mnctioning, as ncu-
rotransmittcrs wcrc discovcrcd, morc powcrml clcctron microscopcs allowcd
thc visualization of synapscs and othcr ccllular structurcs, and sophisticatcd
chcmical probcs allowcd scicntists to work out thc mcchanisms by which
ncurons grow and communicatc with cach othcr. Lndcrstanding continucs
to grow conccrning thc hnc dctails of how ncurons dcvclop and link to and
communicatc with cach othcr through complcx nctworks, and how brain
cclls and thcir nctworks adapt and changc in thc living organism in rcsponsc
to cxpcricncc.
ow, ncw tcchnologics fr brain imaging pcrmit scicntists to scc thc
brain at work in living pcrsons fr thc hrst timc. Thcsc imaging tcchnigucs
can tracc changcs in blood flow within thc brain, locatc arcas that arc hy-
pcractivc or abnormally low in activity, and dctcct abnormally high or ab-
normally low lcvcls of brain chcmicals such as scrotonin and dopaminc.
This infrmation is rcvcaling how thc intcrplay of activity bctwccn dihcrcnt
brain arcas is important in thc rcgulation of mood and is making it possiblc
to idcnti thc rcsponsiblc circuitry. With thc ncw tcchnigucs, wc can scc
how thc brain of a pcrson with a mood disordcr mnctions dihcrcntly hom
that of a pcrson who docs not havc thc disordcr. Pcrhaps an cvcn grcatcr
bcncht will rcsult bccausc wc can scc thc changcs that occur in thc brain
whcn a pcrson rcccivcs trcatmcnt and is bcginning to fccl wcll again. Trans-
cranial magnctic stimulation and dccp brain stimulation fr thc trcatmcnt
of mood disordcrs camc about bccausc of advanccs in ncuroscicncc. nc
can arguc that thcsc ncw brain-stimulation tcchnigucs arc a dircct rcsult of
ncuroscicncc rcscarch, thcy rcprcscnt thc vcry hrst psychiatric trcatmcnts
that wcrc dcvclopcd bascd on scicncc and rcscarch rathcr than stumblcd
upon accidcntally.
Thc sccond scicntihc disciplinc is thc hcld of ycnc||cs. Hcrc again, it is
thc dcvclopmcnt of ncw biochcmical mcthods and molccular probcs that has
madc thc ncw rcscarch possiblc. With thc announccmcnt that thc Human
Ccnomc Projcct had mappcd all of thc gcnctic matcrial in thc human chro-
mosomcs, a ncw cra in thc undcrstanding of gcnctics bcgan. Thc discovcry
of ncw gcncs is announccd cvcry day, and it is only a mattcr of timc bcfrc
thc gcnctic mcchanisms of mood disordcrs arc unravclcd. 5ut thc idcntih-
cation of thc gcncs rcsponsiblc fr mood disordcrs is only onc of thc goals
of work in this hcld. [ust as important will bc undcrstanding thc cpigcnctic
mcchanisms by which gcncs turn on and oh and othcr mcchanisms that
rcgulatc thc cxprcssion and work of thc instructions cncodcd in thc OA
Thc hrst gcnctic approach to pay oh in changing trcatmcnt is likcly to bc
barmaccycncm|cs,thc hcld within gcnctics that invcstigatcs gcnctic fctors
associatcd with rcsponscs to particular pharmaccuticals rathcr than with
risk of discasc. Thc promisc of pharmacogcnomics is that thcrapcutic agcnts
can bc rationally sclcctcd, bascd on a pcrson`s gcnctic prohlc rathcr than
1LLK1iL H1 M 2j1
thc trial- and-crror proccss paticnts must now cndurc. In thc not-too- distant
mturc, a blood tcst will show whcthcr lithium or valproatc or lamotriginc
or somc as yct undiscovcrcd drug will bc thc bcst trcatmcnt fr a particular
individual with bipolar disordcr. A blood tcst may bc ablc to idcnti thc
bipolar paticnts who can safcly takc an antidcprcssant.
As thc gcnctic basis of thc mood disordcrs is discovcrcd, it may turn out
that our classihcation systcm fr thcsc disordcrs is all wrong and a wholc
ncw diagnostic systcm will bc nccdcd fr psychiatric illncsscs, pcrhaps onc
bascd on thc gcncs that arc involvcd in individual paticnts. Instcad of "bi-
polar disordcr II wc may bc diagnosing paticnts with somcthing likc "OISC
I disordcr,' a diagnostic labcl dcrivcd hom thc namc of a gcnc. '
Thc two hclds of ncuroscicncc and psychiatric gcnctics arc closing in on
thc causcs and mcchanisms of mood disordcrs hom dihcrcnt dircctions. As
thcsc two cntcrpriscs advancc, thcy will bcgin to infrm cach othcr-that is,
advanccs in onc hcld will lcad to advanccs in thc othcr. Thc discovcry that a
gcnc fr a particular protcin is linkcd to a mood disordcr will tcll ncurosci-
cntists that that protcin is important in thc rcgulation of mood. Thc discov-
cry of an cnzymc in ncurons that is important in ncuroplasticity, thc proccss
of ncuronal rctuning that appcars to go awry in mood disordcrs, will tcll
gcncticists to fcus on thc gcnc fr that cnzymc in thcir association studics.
Littlc by littlc thc wholc picturc will bccomc incrcasingly clcar.
As our undcrstanding of thc biology of mood disordcrs improvcs, wc
gct closcr to bcttcr diagnostic mcthods and safcr and morc chcctivc trcat-
mcnts. Thc numbcr of ncw mcdications continucs to grow, and many morc
ncw pharmaccuticals arc "in thc pipclinc,' somc of thcm bascd on clucs
about thc biological causcs of thcsc illncsscs . Thc cra of hnding ncw mcdica-
tions csscntially by accidcnt may bc coming to a closc, soon wc will bc ablc
to dcsign trcatmcnts morc chcctivcly and morc rationally. Morc sophisti-
catcd usc of nonpharmaccutical trcatmcnts such as transcranial magnctic
stimulation may makc it possiblc to usc lowcr doscs of mcdications or may
hclp mcdications work morc guickly.
As wc takc thc stcp hom isolating gcncs to dctcrmining thc mnction of
thosc gcncs, thcrc is thc possibility of ycnc|bcray:rcpairing thc codc in thc
OA that causcs mood disordcrs . Thc obstaclcs to bc ovcrcomc bcfrc wc
can look fr this typc of curc can only bc callcd monumcntal, cvcn daunting.
5ut scicntists arc lcarning morc and morc about thcsc illncsscs, and with
cnough timc and cnough hard work, a curc might bc possiblc.
As thc mcchanisms of illncss dcvclopmcnt bccomc known and thc gc-
nctic vulncrabilitics arc idcntihcd, anothcr cxciting possibility cmcrgcs. rc-
vcn||cn. Ccnctic data and a bcttcr undcrstanding of what triggcrs thc illncss
may allow thc dcvclopmcnt of programs aimcd at prcvcnting thc dcvclop-
2j2 M L1iL V i1 SY1iL 11
mcnt of illncss in individuals known to bc at highcr risk fr a particular
So, thcrc is much rcason to cxpcct grcat stridcs in our ability to diag-
nosc and chcctivcly trcat bipolar disordcr. 5ut wc havc a|rcady madc grcat
stridcs-individuals with bipolar disordcr must not lct dcnial or fcar stand
in thc way of taking advantagc of thc vcry good trcatmcnts that arc now
availablc. Ignorancc is no cxcusc, cithcr. Support organizations providc up-
to- datc infrmation about bipolar disordcr through ncwslcttcrs, brochurcs,
wcbsitcs, and, most importantly, in thc support groups thcy sponsor [scc
thc list of rcsourccs that fllows this chaptcr) . With thc cvcr-growing onlinc
rcsourccs now availablc, anyonc with acccss to a computcr can, with thc
click of a mousc, gct thc vcry latcst infrmation on ncw pharmaccuticals
and othcr trcatmcnts.
Likc many othcr scrious illncsscs, bipolar disordcr can bc lifc-thrcatcn-
ing. Lnlikc somc othcrs, howcvcr, it has a uniguc capacity to rob individuals
of thcir spirit, to takc ovcr thcir humanity. And yct, somc of its suhcrcrs havc
takcn inspiration hom thcir strugglc with this illncss to producc music and
art and litcraturc that havc inspircd and cxhilaratcd thc world.
Pcoplc with bipolar disordcr hcgucntly ask mc, Will I havc to takc mcd-
ication fr thc rcst of my lifc I always tcll thcm that no onc knows thc an-
swcr to that gucstion bccausc no onc knows cxactly what thc trcatmcnt of
mood disordcrs might bc in thc mturc. Pcdiatricians practicing in thc Ios
probably could not havc imagincd that vaccincs would onc day practically
climinatc diphthcria, polio, mcaslcs, and othcr childhood discascs, thc com-
mon, hcgucntly crippling, and somctimcs ftal illncsscs thcy diagnoscd so
hcgucntly in thcir paticnts but wcrc so hclplcss to trcat. Thc astonishing
dcvclopmcnts in ncuroscicncc and gcnctics hold just this much promisc fr
pcoplc amictcd with mood disordcrs. Thcrc is cvcry rcason to cxpcct that
thc timc is not too fr oh whcn trcatmcnts fr bipolar disordcr will bc morc
chcctivc than wccan now imaginc.
1LLK1iL H1 M 2jj
Barondes, Samuel H. Mccd Ccncs. Hun|/ny {cr |bc Or/y/ns c{ Man/a and Dcrcss/cn.
New York. Oxford University Press, :.
A clearly written and engrossing account of the tough science involved in the
search fr the genetic basis of mood disorders. An excellent introduction to the
science of genetics.
Cheney, Terry. Man/c. A Mcmc/r. New York. William Morrow, zoo.
Ti s is not an easy read. Words like brutal" and uninching" capture the au-
thor's no-holds-barred descriptions of the terri(ng journey that she traveled
with her illness befre achieving acceptance and the cautious but persistent op-
timism and steely determination that now sustain her. Not fr the faint of heart
but truly inspirational.
Goodwin, Frederick K., and Kay Redneld }amison. Man/c-Dcrcss/vc I||ncss and Rc-
currcn| Dcrcss/cn, znd ed. New York. Oxford University Press, zoo;.
Comprehensive. Encyclopedic. Maybe more than a little overwhelming but a
great resource. Tis :,zoo-plus page tome probably doesn't need to be on your
bookshelf unless you're a clinician, but it may be nice to know where you can
get your hands on a copy to borrow to nnd the answer to that obscure question
about mood disorders that no one else seems to have.
}amison, Kay Redneld. 1cucbcd w/0 I/rc. Man/c-Dcrcss/vc I||ncss and |bc Ar|/s|/c
1cmcramcn|. New York. Free Press, :.
A thoroug survey of creative individuals who sunered hom bipolar disorder,
and an excellent discussion of the connections between creativty and mood
}amison, Kay Redneld. An |nqu/c| M/nd. A Mcmc/r c{ Mccds and Madncss. New
York. Vintage Books, :.
A powerml and moving narrative written with grace and wit by an international
eert on the illness who suners hom it herself. Tis treasure of a book contains
some of the most engrossing and vvd descriptions of the eerience of bipolar
disorder ever written. A must read" fr anyone touched by bipolar disorder.
Kraepelin, Emil. Man/c-Dcrcss/vc Insan/|y and Paranc/a. Trans. R. M. Barclay, ed.
G. M. Robertson. :z:, reprint, New York. Arno Press, :;.
Many college and university libraries have a copy of this book. Arguably the
very nrst textbook on the illness ever written, it is dennitely worth reading.
Miklowitz, Davd. 1c /c|ar D/scrdcr Surv/va| Cu/dc. Wa| cu and cur Iam/|y
Nccd |c Kncw, znd ed. New York. Guilfrd Press, zo:o.
Tis book emphasizes the patient's role in managing bipolar disorder symp-
toms, in simple and easy-to-understand terms. A good introduction.
Mondimore, Francis Mark. Adc|csccn| Dcrcss/cn. A Cu/dc {cr Parcn|s. Baltimore.
}ohns Hopkins University Press, zooz.
OK, I'm biased in mvor of this one. But if you're looking fr a book that fcuses
on the diagnosis and treatment of mood disorders and coping with them in-
cluding bipolar disorder) in young people, I think this is the one to buy'
Noonan, Susan }. Manay/ny cur Dcrcss/cn. Wa| cu Can Dc |c Icc| c||cr. Balti-
more. }ohns Hopkins University Press, zo:.
Tis slim volume is packed with truly helpml advice about managing the symp-
toms of depression, infrmed by the author's own struggle with a depressive
illness as well as her eertise as a physician and background in public health.
Dr. Noonan doesn't just oner suggestions but lays out exercises and lifestyle
recommendations that are concise and eminently practical. All are presented
simply, compassionately, and in small, realistic steps that recognize how dim-
cult it is fr a depressed person to get things done.
Rosenthal, Norman E. W/n|cr |ucs. Scascna| A_cc|/vc D/scrdcr Wa| I| Is and Hcw
|c Ovcrccmc I|. New York. Guilfrd Press, :.
A comprehensive and higly readable discussion of seasonal anective disorder.
Sapols|, Robert M. Wy Zc|ras Dcn`| Cc| ||ccrs. New York. Holt, zoo|.
A very accessible overvew of the biology of stress, the impact stress has on
physical and mental health, and what you can do about it.
Styron, William. Dar/ncss \/s/||c. A Mcmc/r c{ Madncss. New York. Random House,
I recommend this book t o medical students as one of the best accounts of the
symptoms of depression available. A good book fr family members to read to
better understand the experience of serious depression.
1c LanccI 5cr|c: 0n b|0|ur U|:0rJcr
In thc spring of 2OIj, this thrcc- part scrics of rcvicw articlcs appcarcd in
onc of thc world's oldcst and most prcstigious mcdical j ournals, 7cIancc|.
Thcsc thrcc articlcs by a tcam oflcading intcrnational cxpcrts arc writtcn fr
physicians and scicntists, but anyonc and cvcryonc with an intcrcst in this
illncss will lcarn somcthing by glancing through thcm. This is a comprc-
hcnsivc rcsourcc covcring ncarly cvcry aspcct of thc illncss in about thirty
pagcs. You can acccss thc articlcs through most univcrsity librarics and
many public librarics as wcll.
Cradock, Neil, and Pamela Sklar. Genetics of Bipolar Disorder,' Iancc|, :, no.
; zo: ). :|-z.
A comprehensive update of the research into the genetic underpinnings of the
illness. Althoug this article requires at least a working knowledge of genetics
to mlly understand and appreciate it, its optimistic conclusion is crystal cear.
the ongoing major investments of time and money in molecular genetic stud-
ies of psychiatric disorders have the potential to . . . help psychiatry move to-
wards approaches to diagnosis and treatment that are grounded in a better un-
derstanding . . . . Such progress would help to revolutionize clinical psychiatry,
and would be of great benent to patients'
Phillips, Mary, and David Kupfer. Bipolar Disorder Diagnosis. Challenges and Fu-
ture Directions,' Iancc|, :, no. ; zo:) . :-;:.
Tis is perhaps the most thought-provoking of the three articles. It calls fr an
entirely new way of classi(ing mood disorders by using the biosignatures" of
illness types that neuroscience and imaging research are beginning to reveal
rather than symptoms to come up with completely new categories.
Geddes, }ohn, and Davd Miklowitz. Treatment of Bipolar Disorder,' Iancc|, :,
no. ; zo:) . :;z-z.
An overvew of treatment issues with an emphasis on treatments that are usu-
ally not emphasized enoug. psychotherapy and counseling. An excellent over-
vew of the studies showing the benents of dinerent tyes of psychotherapy, in-
cluding CBT, as well as treatments that fcus on family issues, education about
the illness, and indivdualized case management.
All of thc fllowing organizations providc infrmation and rcsourccs, and
somc ohcr rcfcrrals to support groups as wcll as to clinicians in your com-
munity who arc skillcd in trcating mood disordcrs. Contact thcm all and
bccomc a mcmbcr of cach| In addition to thc dircct scrviccs thcy providc
to consumcrs, thcy arc activc in combating thc stigmatization of psychiatric
illncsscs, in lobbying fr bcttcr mcdical insurancc covcragc fr psychiatric
disordcrs, and in supporting rcscarch.
Depression and Bipolar Support Alliance DBSA)
;o North Franklin Street
Chicago, IL o:o
oo- z- NDMDA
www.dbsalliance. org
National Alliance fr the Mentally Ill NAMI)
Colonial Place
z:o; Wilson Blvd. , Suite oo
Arlington, VA zzzo:
oo- o- z|
National Mental Health Association NMHA)
zoo: N. Beauregard Street
:zth Floor
Alexandria, VA zz::
oo- -NMHA
All of thc support and advocacy groups listcd i n thc prcvious scction havc
wcbsitcs, and thc astonishing rangc of rcsourccs on thc Intcrnct continucs to
grow. Rcmcmbcr, howcvcr, that inaccuratc infrmation, bias, and just plain
nonscnsc can also bc fund on thc Intcrnct. It is important to considcr in-
frmation sourccs vcry carcmlly.
Hcrc arc somc cxccllcnt rcsourccs.
International Society fr Bipolar Disorders
www. isbd. org
For scientists and clinicians specializing in bipolar disorders, the site also lists
the latest research articles on bipolar disorder research hom around the world.
www. medscape. com
Tis is primarily a news site fr medical professionals, but it also has a patient
infrmation' section with many useml articles and links to other resources.
Pub Med
www. ncbi. nlm.nih. gov/entrez/query6gi
Free access to the most comprehensive medical database in the world, maintained
by the US. National Library of Medicine. Anyone can use PubMed to search
through : million scientinc journal citations on any medical topic. Te vast ma-
jority of the citations include an abstract short summary) of the article, and your
local public library can o6en help you obtain a copy of the complete tex.
One of the best sources of infrmation on just about any medical problem.
Organized into Condition Centers,' including centers fr bipolar disorder and
depression, that pull together many resources fr common illnesses.
1. For a discussion of the diagnosis of bipolar disorder i n these historical per-
sonalities, see Kay Redneld }amison, 1cucbcd w/0 I/rc. Man/c-Dcrcss/vc I||ncss and
|bc Ar|/s|/c 1cmcramcn| New York. Free Press, :) .
z. Gabor Keitner, Ivan Miller, M. Tracie Shea, and Martin Keller, Course of
Illness and Maintenance Treatments fr Patients with Bipolar Disorder,' )curna| c{
C|/n/ca| Psycb/a|ry , no. : :). -:.
. National Survey of NDMDA Members Finds Long Delay in Diagnosis of
Manic-Depressive Illness,' in News and Notes,' Hcs/|a| and Ccmmun/|y Psycb/a|ry
||, no. :). oo-o:.
|. Frederick K. Goodwin and Kay Redneld }amison, Man/c-Dcrcss/vc I||ncss
New York. Oxrd University Press, :o ), zz.
1 . Wc|s|crs 1/rd Ncw In|crna|/cna| D/c|/cnar |na|r/dycd, s.v. mood,' http. //
unabridged. merriam-webster. com.
z. Although I have made these clinical vgnettes as realistic as possible by using
symptom details culled hom many patients, they are nctitious and do not portray
any person, livng or dead.
. Te word man/a has ancient origins, derivng hom the Greek word ma/ncs-
|ba/, which means simply to be insane' Very early English physicians sometimes
used the word madncss to describe the syndrome of disorganized hyperactivty that
we now call mania. But during the eighteenth and nineteenth centuries, European
physicians writing about mental disorders increasingly employed man/a in French
|a man/c and in German d/c Man/c). When Emil Kraepelin used man/c-dcrcss/vc
/nsan/|y in his groundbreaking work on bipolar disorder, the term man/a fr the
excited phase of the disorder became nrmly established.
|. Henry }. Berkley, A 1rca|/sc cn Mcn|a| D/scascs :oo, reprint, New York.
Arno Press, :o ), :|.
. Kay Redneld }amison, An |nqu/c| M/nd. A Mcmc/r c{ Mccds and Madncss
New York. Vintage Books, :) , .
. Frederick K. Goodwin and Kay Redneld }amison, Man/c-Dcrcss/vc I||ncss
New York. Oxford University Press, :o ), z.
;. Quoted in ibid. , z-z;.
. Emil Kraepelin, Man/c-Dcrcss/vc Insan/|y and Paranc/a, trans. R. M. Bar-
clay, ed. G. M. Robertson :z:, reprint, New York. Arno Press, :;) , :. Tis is a
translation of volumes and | of the th edition ::) of Kraepelin's textbook Psy-
cb/a|r/c, which originally appeared in :.
. Goodwin and }amison, Man/c-Dcrcss/vc I||ncss, z.
:o. Kraepelin, Man/c-Dcrcss/vc Insan/| :.
::. For a discussion of the concept of motivated behavors in psychiatry, see
Paul McHugh and Philip Slavney, 1c Pcrscc|/vcs c{ Psycb/a|ry Baltimore. }ohns
Hopkins University Press, :) , ::-z.
:z. Kraepelin, Man/c-Dcrcss/vc Insan/| z.
:. Ibid. , , |.
:|. }. D. Campbell, Man/c-Dcrcss/vc D/scasc. C|/n/ca| and Psycb/a|r/c S/ynq-
cancc Philadelphia. }. D. Lippincott, :) , :-o, quoted in Goodwin and }amison,
Man/c-Dcrcs/vc I||ncss, z|.
:. }amison, |nqu/c| M/nd, .
:. Kraepelin, Man/c-Dcrcss/vc Insan/| ;o.
:;. Berkley, 1rca|/sc cn Mcn|a| D/scascs, :o.
:. Gabrielle Carlson and Frederick Goodwin, Te Stages of Mania,' Arcb/vcs
c{ Ccncra| Psycb/a|ry z :;) . zz:-z.
:. Quoted in Edward Hare, Te Two Manias. Study of the Evolution of the
Modern Concept of Mania,' r/|/sb )curna| c{ Psycb/a|ry : ::). -.
zo. Norman Endler, Hc|/day c{ Dar/ncss. A Psycbc|cy/s|s Pcrscna| )curncy cu|
c{ H/s Dcrcss/cn New York. }ohn Wiley and Sons, :z), |.
z:. Ibid. , .
zz. William Styron, Dar/ncss \/s/||c. A Mcmc/r c{ Madncss New York. Ran-
dom House, :o) , :.
z . Endler, Hc|/day c{ Dar/ncss, |-|.
z|. }ohann Wolfgang von Goethe, 1c Scrrcws c{ cuny Wcr|bcr trans. Eliza-
beth Mayer and Louise Bogan New York. Random House, :;:), ::|.
z. Quoted in Kay Redneld }amison, 1cucbcd w/|b I/rc. Man/c-Dcrcss/vc I||ncss
and |bc Ar|/s|/c 1cmcramcn| New York. Free Press, :), z:.
z. Styron, Dar/ncss \/s/||c, :;.
z;. Endler, Hc|/day c{ Dar/ncss, z.
z. Kraepelin, Man/c-Dcrcss/vc Insan/| ;.
z. Scott Fitzgerald, 1c Crac/u New York. New Directions, :) , ;.
22 M iLS L PLS -l1
o. Styron, Dar/ncss \/s/||c, :;.
:. Endler, Hc|/day c{ Dar/ncss, |.
z. Styron, Dar/ncss \/s/||c, ||.
. Endler, Hc|/day c{ Dar/ncss, |.
|. Kraepelin, Man/c-Dcrcss/vc Insan/| |.
. Ibid. , .
. Styron, Dar/ncss \/s/||c, .
;. Kraepelin, Man/c-Dcrcss/vc Insan/| ;.
. }amison, |nqu/c| M/nd, |.
. Kraepelin, Man/c-Dcrcss/vc Insan/| :o|.
|o. Because some patients in an otherwise typical manic episode develop des-
perate, anxious, distraugt symptoms as they become sicker, some researchers have
made the case that mixed states can be thought of as a very severe stage of mania
Stage III mania' as described in the section Mania' ) .
|:. Kraepelin, Man/c-Dcrcss/vc Insan/| .
1 . Frederick K. Goodwin and Kay Redneld }amison, Man/c-Dcrcss/vc I||ncss
New York. Oxfrd University Press, :o ), :z.
z. Modern diagnostic classincations are usually dinerent hom those that were
used when these older studies were done. In most cases, however, patients with
manic-depressive illness" in these studies had mll-blown manic episodes and se-
vere depressions and thus would today probably be diagnosed with bipolar I. Never-
theless, cases that would today be diagnosed dinerently as bipolar II, fr example)
may have been mixed in. Tus, the nndings and statistics must be interpreted with
some caution.
. Tomas A. C. Rennie, Prognosis in Manic-Depressive Psychosis,' Amcr/can
)curna| c{ Psycb/a|ry :|z). o:-:|, quoted in Goodwin and }amison, Man/c-
Dcrcss/vc I||ncss, :.
|. Emil Kraepelin, Man/c-Dcrcss/vc Insan/|y and Paranc/a, trans. R. M. Bar-
clay, ed. G. M. Robertson :z:, reprint, New York. Arno Press, :;) , :.
. Ibid. , , :;.
. G. Winokur, P. Clayton, and T. Reich, Man/c-Dcrcss/vc I||ncss St. Louis.
C. N Mosby, : ), quoted in Goodwin and }amison, Man/c-Dcrcss/vc B|ncss, :|:.
;. Athansio Koukopoulas, Daniela Reginaldi, Giampolo Minnai, Gino Serre,
Luca Pani, and Neil }ohnson, Te Long Term Prophylaxis of Anective Disorders,'
in Dcrcss/cn and Man/a. Ircm Ncurc|/c|cg |c 1rca|mcn|, ed. G. Gessa, Y Fratta,
L. Pina, and G. Serre New York. Raven Press, :), :z;-|;.
. William Coryell, Nancy Andreasen, }ean Endicott, and Martin Keller, Te
Signincance of Past Mania or Hypomania in the Course and Outcome of Major De-
pression,' Amcr/can )curna| c{ Psycb/a|ry :|| :;). o-:.
. Sylva Simpson, Susan Folstein, Deborah Meyers, Francis McMahon, Diane
Brusco, and }. Raymond DePaulo, Bipolar II. Te Most Common Bipolar Pheno-
typer" Amcr/can )curna| c{ Psycb/a|ry :o :). o:-.
:o. }. H. Baek, D. Y. Park, }. Choi, }. S. Kim, }. S. Choi, K. Ha, }. S. Kwon, and
iLS L PLS ll-qO M 2j
K. S. Hong, Dinerences between Bipolar I and Bipolar II Disorders in Clinical Fea-
tures, Comorbidity and Family History,' )curna| c{ A_cc|/vc D/scrdcrs :: zo::).
::. Ibid.
:z. Hagop Akiskal, }ack Maser, Pamela Zeller, }ean Endicott, William Coryell,
Martin Keller, Meredith Warshaw, Paula Clayton, and Frederick Goodwin, Switch-
ing hom 'Unipolar' to Bipolar II. An Eleven-Year Prospective Study of Clinical and
Temperamental Predictors in Patients,' Arcb/vcs c{ Ccncra| Psycb/a|ry z :).
:. Eduard Vieta and Trisha Suppes, Bipolar II Disorder. Arguments fr and
against a Distinct Pathological Entity,' /c|ar D/scrdcrs :o zoo) . :-;.
:|. Kraepelin, Man/c-Dcrcss/vc Insan/| ::.
:. Hagop S. Akiskal, Te Prevalent Clinical Spectrum of Bipolar Disorders.
Beyond DSM-IV' )curna| c{ C|/n/ca| Psycbc barmacc|cg :, suppl. :) . |S-:|S.
:. Kraepelin, Man/c-Dcrcss/vc Insan/| :z.
:;. H. Akiskal, M. K. Khani, and A. Scott-Strauss, Cycothymic Temperamental
Disorders,' Psycb/a|r/c C|/n/cs c{ Ncr|b Amcr/ca z :;). z;-|.
:. Robert Howland and Michael Tase, A Comprehensive Revew of Cyco-
thymic Disorder,' )curna| c{ Ncrvcus and Mcn|a| D/scasc :: :). |-.
:. Akiskal, Prevalent Clinical Spectrum of Bipolar Disorders''
zo. Howland and Tase, Comprehensive Review of Cycothymic Disorder'
z:. Kraepelin, Man/c-Dcrcss/vc Insan/| z.
zz. Hagop Akiskal and Gopinath Mallya, Criteria fr 'So6' Bipolar Spectrum.
Treatment Implications,' Psycbcbarmacc|cg u||c|/n z, no. : :;). -;.
z. Akiskal, Prevalent Clinical Spectrum of Bipolar Disorders'
z|. See Goodwin and }amison, Man/c-Dcrcss/vc I||ncss, :-.
z. R. Y Cowdry, T. A. Wehr, A. Zis, and K. Goodwin, Tyroid Abnormal-
ities Associated with Rapid Cycling Bipolar Illness,' Arcb/vcs c{ Ccncra| Psycb/a|ry
|o :). |:|-zo, and T. A. Wehr and K. Goodwin, Rapid Cycling in Manic-
Depressives Induced by Tricycic Antidepressants,' Arcb/vcs c{ Ccncra| Psycb/a|ry
:; ) . -.
z. A. Koukopoulas, B. Caliari, A. Tundo, G. Floris, D. Reginaldi, and L. Tondo,
Rapid Cycers, Temperament, and Antidepressants,' Ccmrcbcns/vc Psycb/a|ry z|,
no. :) . z|-.
z;. William Coryell, }ean Endicott, and Martin Keller, Rapid Cycling Bipolar
Disorder. Demographics, Diagnosis, Family History, and Course,' Arcb/vcs c{ Ccn-
cra| Psycb/a|ry | :z). :z-:.
1 . At the time, epilepsy was considered t o be a mental illness.
z. Alhed Kinsey, Wardell Pomeroy, and Clyde Martin, Scxua| cbav/cr /n |bc
Human Ma|c Philadelphia. Y B. Saunders, :|), ;, .
2q M iLS L PLS qO-])
1. Quoted i n Stanley Y }ackson, Mc|ancbc|/a and Dcrcss/cn, {cm H/ccra|/c
1/mcs |c Mcdcrn 1/mcs New Haven, CT. Yale University Press, :), z: peevish,'
complained[ ,' and At the height"), and in Frederick K. Goodwin and Kay Redneld
}amison, Man/c-Dcrcss/vc I||ncss New York. Oxford University Press, :o ), In
my opinion'' ) .
z. Quoted i n }ackson, Mc|ancbc|/a and Dcrcss/cn, z-|.
. Quoted in ibid. , z;.
|. See ibid. , zz-.
. Emil Kraepelin, Man/c-Dcrcss/vc Insan/|y and Paranc/a, trans. R. M. Barclay,
ed. G. M. Robertson :z:, reprint, New York. Arno Press, :;) , 1.
. }ackson, Mc|ancbc|/a and Dcrcss/cn, z;z.
;. Henry }. Berkley, A 1rca|/sc cn Mcn|a| D/scrdcrs :oo, reprint, New York.
Arno Press, :o ), :;.
. }ohn }. Cade, Lithium Salts in the Treatment of Psychotic Excitement,'
Mcd/ca| )curna| c{ Aus|ra|/a :| ). |-z.
. Ibid. , o-:.
:o. It turns out that }ohn Cade was not the nrst psychiatrist to give lithium to
patients with mood disorders. More than n6y years earlier, the Danish psychiatrist
brothers Carl and Friedrich Lange had used lithium salts to treat patients with de-
pression and had seen some success. Te Lange brothers wrote about this discovery
in a German psychiatric research journal, but their report did not garner much at-
tention and was not translated into other languages. It had been essentially frgotten
by the time Cade started his work.
::. For a superb account of this shameml story, see Gtz Aly, Peter Chroust, and
Christian Pross, C|cans/ny |bc Ia|bcr|and. Naz/ Mcd/c/nc and Rac/a| Hyy/cnc Balti-
more. }ohns Hopkins University Press, :|).
:z. Ronald R. Fieve, Mccdsw/ny 1c 1/rd Rcvc|u|/cn /n Psycb/a|ry New York.
Bantam Books, :;), .
:. M. Schou, N. }uel-Nielsen, E. Strmgren, and H. Voldby, Te Treatment
of Manic Psychoses by the Administration of Lithium Salts,' )curna| c{ Ncurc|cg
Ncurcsurycr and Psycb/a|ry :; :|). zo-o.
:|. Roland Kuhn, Te Treatment of Depressive States with G zz Imipra-
mine Hydrochloride) ,' Amcr/can )curna| c{ Psycb/a|ry :: :). |-|, at |:.
:. Schou, }uel-Nielsen, Strmgren, and Voldby, Treatment of Manic Psycho-
ses,' z. Emphasis added.
1. Nancy C. Andreasen, 1c rc/cn ra/n. 1c /c|cy/ca| Rcvc|u|/cn / n Psycb/a-
|ry New York. Harper and Row, :).
z. R. }. Schloesser, }. Huang, S. Klein, and H. K. Manji, Cellular Plasticity
Cascades in the Pathophysiology and Treatment of Bipolar Disorder,' Ncurcsycbc-
barmacc|cg zoo) . ::o-.
iLS L PLS ]-) M 2j
1 . Anastase Georgotas and Samuel Gershon, Historical Perspectives and Cur-
rent Highligts on Lithium Treatment in Manic-Depressive Illness,' )curna| c{ C|/n-
/ca| Psycbcbarmacc|cyy :, no. : ::). z;-:.
z. Paul Baalstrup and Morgans Schou, Lithium as a Prophylactic Agent. Its
Enect against Recurrent Depressions and Manic-Depressive Psychosis,' Arcb/vcs c{
Ccncra| Psycb/a|ry :, no. z :;). :z-;z.
. B. Blackell and M. Shephard, Prophylactic Lithium. Another Terapeutic
Mythr" Iancc| : :) . -;:.
|. P. Baalstrup, }. Poulsen, M. Schou, K. Tomsen, and A. Amdisen, Prophy-
lactic Lithium. Double-Blind Discontinuation in Manic and Recurrent-Depressive
Disorders,' Iancc| z :;o) . z-o.
. American Psychiatric Association, Practice Guidelines fr the Treatment of
Bipolar Disorder,' Amcr/can )curna| c{ Psycb/a|ry ::, suppl. :|). .
. To be more precise, the therapeutic index is the ratio of the largest dose pro-
ducing no toxic symptoms t o the smallest dose routinely producing the desired ther-
apeutic enects.
;. Alan Gelenberg, }ohn Kane, Martin Keller, Phillip Lavori, }errold Rosen-
baum, Karyl Cole, and }anet Lavelle, Comparison of Standard and Low Levels of
Lithium fr Maintenance Treatment of Bipolar Disorder,' Ncw Eny|and )curna| c{
Mcd/c/nc z:, no. zz :) . :|-.
. Morgans Schou, Forty Years of Lithium Treatment,' Arcb/vcs c{ Ccncra| Psy-
cb/a|ry | :;). -:.
. Ibid. , ::.
:o. R. }. Knebel, N. Rosenlicht, and L. Collins, Lithium Carbonate Mainte-
nance Terapy in a Hemodialysis Patient with End-Stage Renal Disease,' Amcr/can
)curna| c{ Psycb/a|ry :;, no. :: zo:o ). :|o-:o.
::. For an excellent review, see T. }. Raedler and K. Wiedermann, Lithium-
Induced Nephropathies,' Psycbcbarmacc|cg u||c|/n |o, no. z zoo;). :|-|.
:z. American Psychiatric Association, Practice Guidelines fr the Treatment
of Bipolar Disorder,' ;.
:. Frederick K. Goodwin and Kay Redneld }amison, Man/c-Dcrcss/vc I||ncss
New York. Oxfrd University Press, :o ), ;o;.
:|. }onathan Sporn and Gary Sachs, Te Anticonvulsant Lamotrigine in Treat-
ment-Resistant Manic-Depressive Illness,' )curna| c{ C|/n/ca| Psycbcbarmacc|cyy
:;, no. :;). :-.
:. }oseph R. Calabrese, S. Hossein Fatemi, and Mark }. Woyshvlle, Antide-
pressant Enects of Lamotrigine in Rapid Cycling Bipolar Disorder,' Amcr/can )cur-
na| c{ Psycb/a|ry :, no. :). :z.
:. C. L. Bowden, }. R. Calabrese, G. Sachs, L. N. Yatham, S. A. Asgar, M. Homp-
land, P. Montgomery, N. Earl, T. M. Smoot, and }. DeVeaugh-Geiss Lamictal o
Study Group), A Placebo- Controlled :-Month Trial of Lamotrigine and Lithium
Maintenance Treatment in Recently Manic or Hypomanic Patients with Bipolar
2 M iLS L PLS ) ) -)
I Disorder,' Arcb/vcs c{ Ccncra| Psycb/a|ry o, no. | zoo) . z, }. R. Calabrese,
C. L. Bowden, G. Sachs, L. N. Yatham, K. Behnke, L. P. Mehtonen, P. Montgomery,
}. Ascher, Y Paska, N. Earl, and }. DeVeaugh-Geiss Lamictal o Study Group) ,
A Placebo- Controlled :-Month Trial of Lamotrigine and Lithium Maintenance
Treatment in Recently Depressed Patients with Bipolar I Disorder,' )curna| c{ C|/n/-
ca| Psycb/a|ry |, no. zoo). :o: -z|.
:;. }. R. Calabrese, }. R. Sullivan, C. L. Bowden, T. Suppes, }. Goldberg,
G. S. Sachs, M. D. Shelton, K. Goodwin, M. A. Frye, and N Kusumakar, Rash
in Multi- Center Trials of Lamotrigine in Mood Disorders. Clinical Relevance and
Management,' )curna| c{ C|/n/ca| Psycb/a|ry , no. :: zooz). :o:z-:.
:. See Charles Bowden and Susan McElroy, History of the Development of
Valproate fr the Treatment of Bipolar Disorder,' )curna| c{ C|/n/ca| Psycb/a|ry ,
suppl. :). -.
:. Charles L. Bowden, Predictors of Response to Divalproex and Lithium,'
)curna| c{ C|/n/ca| Psycb/a|ry , suppl. :). z-z.
zo. D. }. Muzina, K. Gao, D. E. Kemp, S. Khalife, S. }. Ganocy, P. K. Chan,
M. B. Seranno, C. M. Conroy, and }. R. Calabrese, Acute Emcacy of Divalproex
Sodium versus Placebo in Mood-Stabilizer- Nave Bipolar I or Bipolar II Depres-
sion. A Double-Blind, Randomized, Placebo Controlled Trial,' )curna| c{ C|/n/ca|
Psycb/a|ry ;z, no. zo::) . :-:, C. L. Bowden, }. R. Calabrese, S. L. McElroy,
L. Gyulai, A. Wassef, H. G. Pope, }. C. Chou, P. E. Keck, L. }. Rhodes, A. C. Swann,
R. M. Hirshfeld, and P. }. Wozniak, A Randomized, Placebo- Controlled :z-Month
Trial of Divalproex and Lithium in the Treatment of Outpatients with Bipolar I Dis-
order. Divalproex Maintenance Study Group,' Arcb/vcs c{ Ccncra| Psycb/a|ry ;, no.
zooo) . |:-.
z:. K. A. Macritchie, }. R. Geddes, }. Scott, D. R. Haslam, and G. M. Goodwin,
Valproic Acid, Valproate, and Divalproex in the Maintenance Phase of Bipolar Dis-
order,' Cccbranc Da|a|asc c{ Sys|cma|/c Rcv/cws zoo:). Art. No. CDoo:.
zz. American Psychiatric Association, Practice Guidelines fr the Treatment
of Bipolar Disorder,' :o.
z . See Frederick }acobsen, Low-Dose Valproate. A New Treatment fr Cy-
cothymia, Mild Rapid- Cycling Disorders, and Premenstrual Syndrome,' )curna| c{
C|/n/ca| Psycb/a|ry |, no. :). zz-|. Also }. A. Delito, Te Enect ofValproate
on Bipolar Spectrum Temperamental Disorders,' )curna| c{ C|/n/ca| Psycb/a|ry |,
no. :). oo-o|.
z|. Gary Sachs, Bipolar Mood Disorder. Practical Strategies fr Acute and
Maintenance Phase Treatment,' )curna| c{ C|/n/ca| Psycbcbarmacc|cyy :, no. z,
suppl. : :) . zS-|;S.
z. }. C. Ballenger and R. M. Post, Carbamazepine in Manic-Depressive Illness.
A New Treatment,' Amcr/can )curna| c{ Psycb/a|ry :;, no. ; :o) . ;z-o.
z. B. Lerer, M. Moore, E. Meyendorn, S. R. Cho, and S. Gershon, Carbamaze-
pine versus Lithium in Mania. A Double-Blind Study' )curna| c{ C|/n/ca| Psycb/a|ry
|, no. :;). -.
z;. Robert Post, Tomas Uhde, }ames Ballenger, and Kathleen Squillace, Pro-
iLS L PLS - M 2,
phylactic Emcacy of Carbamazepine in Manic-Depressive Illness,' Amcr/can )curna|
c{ Psycb/a|ry :o, no. :z :8). :6oz-.
z8. Ibid.
z. R. H. Weisler, A. H. Kalali, and T. A. Ketter, A Multicenter, Randomized,
Double-Blind, Placebo- Controlled Trial of Exended-Release Carbamazepine Cap-
sules as Monotherapy fr Bipolar Disorder Patients with Manic or Mixed Episodes,'
)curna| c{ C|/n/ca| Psycb/a|ry 6, no. zoo). ;8-8.
o. Centorrino, M. }. Albert, }. M. Berry, }. P. Kelleher, N Fellman, G. Line,
A. E. Koukopoulos, }. E. Kidwell, K. N Fogarty, and R. }. Baldessarini, Oxcarbaze-
pine. Clinical Eerience with Hospitalized Psychiatric Patients,' /c|ar D/scrdcrs
, no. zoo). ;o-;.
:. }oseph Goldberg, Katherine E. Burdick, and Carrie }. Endick, Prelimi-
nary Randomized, Double-Blind, Placebo-Controlled Trial of Pramipexole Added
to Mood Stabilizers fr Treatment-Resistant Bipolar Depression,' Amcr/can )curna|
c{ Psycb/a|ry :6:, no. zoo). 6-66.
z. Michael Berk, Davd Copolov, Oliva Dean, Kristy Lu, Sue }eavons, Ian
Schapkaitz, Murray Anderson-Hunt, and Ashley Bush, N-Acetyl Cysteine fr De-
pressive Symptoms in Bipolar DisorderA Double- Blind Randomized Placebo-
Controlled Trial,' /c|cy/ca| Psycb/a|ry 6, No. 6 zoo8 ) . 68-;, M. Berk, L.Dean, S.
Cotton, C. Gama, Kapczinski, B. Fernandes, K. Kohlmann, S. }eavons, K. Hewett,
C. Allwang, H. Cobb, A. Bush, I. Schapkaitz, S. Dodd, and G. Malhi, Te Emcacy of
N-Acetylcysteine as an Adjunctive Treatment in Bipolar Depression. An Open Label
Trial,' )curna| c{ A_cc|/vc D/scrdcrs :, nos. :- zo::). 8-.
. C. A. Zarate }r. , }. A. Quiroz, }. B. Singh, K. D. Denicon, G. De }esus,
D. A. Luckenbaugh, D. S. Charney, and H. K. Manji, An Open-Label Trial of the
Glutamate-Modulating Agent Riluzole in Combination with Lithium fr the Treat-
ment of Bipolar Depression,' /c|cy/ca| Psycb/a|ry ;, no. zoo) . o-z.
. A. Fan, A. Berg, C. Bresee, L. Glassman, and M. Rapaport, Allopurinol
Augmentation in the Outpatient Treatment of Bipolar Mania. A Pilot Study,' /c|ar
D/scrdcr :, no. z zo:z). zo6-:o.
. Maura L. Furey and Wayne C. Drevets, Antidepressant Emcacy of the Anti-
muscarinic Drug Scopolamine. A Randomized, Placebo-Controlled Clinical Trial,'
Arcb/vcs c{ Ccncra| Psycb/a|ry 6, no. :o zoo6). ::z:-z.
6. Rodrigo Machado-Vieira and Carlos A. Zarate }r. , Proof of Concept Trials
in Bipolar Disorder and Major Depressive Disorder. A Translational Perspective
in the Search fr Improved Treatments,' Dcrcss/cn and Anx/c|y z8, no. zo::).
1. H. S. Lee, D. H. Song, C. H. Kim, and H. K. Choi, An Open Clinical Trial of
Fluoxetine in the Treatment of Premature Ejaculation,' )curna| c{ C|/n/ca| Psycbc-
barmacc|cg :6, no. :6). ;-8z.
z. G. S. Sachs, A. A. Nierenberg, }. R. Calabrese, L. B. Marangell, S. R. Wisniewski,
L. Gyulai, E. S. Friedman, C. L. Bowden, M. D. Fossey, M. }. Ostacher, T. A. Ketter,
2 M iLS L PLS -1O]
}. Patel, P. Hauser, D. Rappaport, and }. M. Martinez, Enectiveness of Adjunctive
Antidepressant Treatment fr Bipolar Depression,' Ncw Eny|and )curna| c{ Mcd/c/nc
6, no. :; zoo;). :;::-zz.
. See ibid. , and R. S. El-Mallakh, S. N. Ghaemi, K. Sagduyu, M. E. Tase,
S. R. Wisniewski, A. A. Nierenberg, H. YZhang, T. A. Pardo, and G. Sachs, STEP-BD
Investigators, Antidepressant-Associated Chronic Irritable Dysphoria ACID) in
STEP- BD Patients,' )curna| c{ A_cc|/vc D/scrdcrs :::, nos. z- zoo8) . ;z-
1. }enrey Lieberman, Allan Sanerman, Simcha Pollack, Sally Szmanski, Celeste
}ohns, Alheda Howard, Michael Kronig, Peter Bookstein, and }ohn Kane, Clinical
Enects of Clozapine in Chronic Schizophrenia. Response to Treatment and Predic-
tors of Outcome,' Amcr/can )curna| c{ Psycb/a|ry ::, no. :z :). :;-z.
z. In a study of ::, patients treated with clozapine, ; developed agranulo-
cytosis of whom z died of the infectious complications of the condition) . See }ose
Alvr, }enrey Lieberman, Allan Sanerman, }enrey Schwimmer, and }ohn Schaaf,
Clozapine-Induced Agranulocytosis. Incidence and Risk Factors in the United
States,' Ncw Eny|and )curna| c{ Mcd/c/nc z :). :6z-6;.
. }oseph R. Calabrese, Herbert 1 Meltzer, and Paul }. Markovitz, Clozapine
Prophylaxis in Rapid Cycling Bipolar Disorder,' )curna| c{ C|/n/ca| Psycbcbarma-
cc|cyy ::, no. 6 ::). 6-;.
. }oseph Calabrese, Susan Kimmel, Mark Woyshville, Daniel Rapport, Carl
Faust, Paul Tompson, and Herbert Meltzer, Clozapine fr Treatment-Refractory
Mania,' Amcr/can )curna| c{ Psycb/a|ry :, no. 6 :6). ;-6.
. Carlos Zarate }r. , Mauricio Tohen, Michael Banov, Michelle Weiss, and }on-
athan Cole, Is Clozapine a Mood Stabilizerr" )curna| c{ C|/n/ca| Psycb/a|ry 6, no.
:). :o8-:z.
6. G. Parker and G. Malhi, Are the Atypical Antipsychotic Drugs Antidepres-
santsr" )curna| c{ C|/n/ca| Psycbc barmacc|cg , no. zooz) . -.
;. T. Baptista, N. M. Kin, S. Beaulieu, and E. A. de Baptista, Obesity and Related
Metabolic Abnormalities during Antipsychotic Drug Administration. Mechanisms,
Management, and Research Perspectives,' Pbarmaccsycb/a|ry , no. 6 zooz).
1. For a discussion of these drugs t o treat anxiety i n bipolar disorder, see
P. E. Keck, }. R. Strawn, and S. L. McElroy, Pharmacologic Treatment Consider-
ations in Co-occuring Bipolar and Anxiety Disorder,' )curna| c{ C|/n/ca| Psycb/a|ry
6;, suppl. : zoo6). 8-:.
z. M. S. Bauer, P. C. Whybrow, and A. Winokur, Rapid Cycling Bipolar Af-
fective Disorder I. Association with Grade I Hypothyroidism,' Arcb/vcs c{ Ccncra|
Psycb/a|ry ;, no. :o ). z;-z.
. H. A. Oomen, A. }. Schipperijn, and H. A. Drexhage, Te Prevalence of Af-
iLS L PLS 1O]-11 M 2
fective Disorder and in Particular of a Rapid Cycling of Bipolar Disorder in Patients
with Abnormal Tyroid Function Tests,' C|/n/ca| Endccr/nc|cg , no. z :6).
. D. P. Cole, M. E. Tase, A. G. Mallinger, }. C. Soares, }. Luther, D. }. Kup-
fer, and E. Frank, Slower Treatment Response in Bipolar Depression Predicted by
Lower Pre-treatment Tyroid Function,' Amcr/can )curna| c{ Psycb/a|ry :, no. :
zooz) . ::6-z:.
. }oseph R. Calabrese and Mark }. Woyshville, A Medication Algorithm fr
Treatment of Bipolar Rapid Cyclingr" )curna| c{ C|/n/ca| Psycb/a|ry 6, suppl.
:). ::-:8.
6. Tere have been controversies as to whether all thyroid hormone prepara-
tions made by dinerent manumcturers are equivalent and interchangeable. Law-
rence K. Altman, Caution Urged over Switch in Tyroid Drug,' Ncw cr/ 1/mcs,
April :;, :;. Te problem can be avoided by making sure that you take the same
preparation oflevothyroxine, whether brand name or generic, all the time, and also
by getting your thyroid hormone levels tested regularly.
;. }. Sarris, D. Mischoulon, and I. Schweitzer, Omega- fr Bipolar Disorder.
Meta-analysis of Use in Mania and Bipolar Depression,' )curna| c{ C|/n/ca| Psycb/a-
|ry ;, no. : zo:z). 8:-86.
8. M. Berk, D. Copoloc, L. Dean, K. Lu, S. }eavons, I. Schapkaitz, M. Ander-
son-Hunt, and A. Bush, N-Acetyl Cysteine fr Depressive Symptoms in Bipolar
DisorderA Double-Blind Randomized Placebo- Controlled Trial,' /c|cy/ca| Psy-
cb/a|ry 6, no. 6 zoo8) . 68-;, M. Berk, L. Dean, S. Cotton, C. Gama, Kap-
czinski, B. Fernandes, K. Kohlmann, S. }eavons, K. Hewerr, C. Allwang, K. Cobb,
A. Bush, I. Schapkaitz, S. Dodd, and G. Malhi, Te Emcacy of N-Acetylcysteine as
an Adjunctive Treatment in Bipolar Depression. An Open Label Trial,' )curna| c{
A_cc|/vc D/scrdcrs :, nos. :- zo::). 8-.
. K. Linde, G. Ramirez, C. D. Mulrow, A. Pauls, and Y Weidenhammer, St.
}ohns Wort fr DepressionAn Overview and Meta- analysis of Randomised Clin-
ical Trials,' r/|/sb Mcd/ca| )curna| :, no. ;oz :6). z-8.
:o. R. C. Shelton, M. B. Keller, A. Gelenberg, D. L. Dunner, R. Hirschfeld,
M. E. Tase, }. Russell, R. B. Lydiard, Crits- Christoph, R. Gallop, L. Todd, D. Hell-
erstein, P. Goodnick, G. Keitner, S. M. Stahl, and U Halbreich, Enectiveness of St.
}ohn's Wort in Major Depression. A Randomized Controlled Trial,' )curna| c{ |bc
Amcr/can Mcd/ca| Asscc/a|/cn z8, no. : zoo:). :;8-86.
::. A. }. Gelenberg, R. C. Shelton, P. Crits- Christoph, M. B. Keller, D. L. Dun-
ner, R. M. Hirschfeld, M. E. Tase, }. M. Russell, R. B. Lydiard, R. }. Gallop, L.
Todd, D. }. Hellerstein, P. }. Goodnick, G. I. Keitner, S. M. Stahl, U Halbreich, and
H. S. Hopkins, Te Enectiveness of St. }ohns Wort in Major Depressive Disorder. A
Naturalistic Phase z Follow- Up in Which Nonresponders Were Provided Alternate
Medication,' )curna| c{ C|/n/ca| Psycb/a|ry 6, no. 8 zoo). :::-:.
:z. E. Moses and A. Mallinger, St. }ohns Wort. Tree Cases of Possible Mania
Induction,' )curna| c{ C|/n/ca| Psycbcbarmacc|cg zo, no. : zooo) . ::-:;.
2,0 M iLS L PLS 11-1l
1. Emil Kraepelin, Man/c-Dcrcss/vc Insan/|y and Paranc/a, trans. R. M. Barclay,
ed. G. M. Robertson :z:, reprint, New York. Arno Press, :;), ;.
z. C. Freeman and R. E. Kendell, ECT I. Patients' Experiences and Attitudes,'
r/|/sb )curna| c{ Psycb/a|ry :; :o ). 8-:6.
. M. Valance, Te Experience of Electro- Convulsive Terapy by a Practising
Psychiatrist,' r/|/sb )curna| c{ Psycb/a|ry ::: :6). 6-6;.
. Larry Squire, Pamela Slater, and Patricia Miller, Retrograde Amnesia and
Bilateral Electroconvulsive Terapy, Long Term Follow-up,' Arcb/vcs c{ Ccncra| Psy-
cb/a|ry ::). -.
. Larry R. Squire and Pamela C. Slater, Electroconvulsive Terapy and Com-
plaints of Memory Dysmnction. A Prospective Tree-Year Follow-up Study,' r/|/sb
)curna| c{ Psycb/a|ry :z :). :-.
6. E. Anderson and I. Reti, ECT in Pregnancy. A Revew of the Literature hom
:: to zoo;,' Psycbcscma|/c Mcd/c/nc ;:, no. z zoo ). z-z.
;. Frederick K. Goodwin and Kay Redneld }amison, Man/c-Dcrcss/vc I||ncss,
znd ed. New York. Oxfrd University Press, zoo;), ;z.
. Sukdeb Mukherj ee, Harold Sackeim, and Davd Schnur, Electroconvulsive
Terapy of Acute Manic Episodes. A Revew of Fi6y Years' Eerience,' Amcr/can
)curna| c{ Psycb/a|ry :: :). :6-;6.
. S. Mukherjee, H. Sackeim, and C. Lee, Unilateral ECT in the Treatment of
Manic Episodes,' Ccnvu|s/vc 1cray | :). ;|-o.
:o. Much of the work comparing the enectiveness of ECT with that of medi-
cation compares it with treatment with lithium. As studies comparing it with treat-
ment using newer agents such as the anticonvulsants) are done, statements about
ECT's superiority to medical treatments fr mania may need to be revsed. However,
given that the new mood stabilizers are perhaps |css enective than lithium fr de-
pression, ECT's claims as a more predictably enective treatment fr bipolar depres-
sion remain unchallenged.
1. See Mark S. George, Eric Wasserman, and Robert Post, Transcranial Mag-
netic Stimulation. A Neuropsychiatric Tool fr the Twenty- First Century,' )curna| c{
Ncurcsycb/a|ry and C|/n/ca| Ncurcsc/cnccs :6). ; -z.
:z. Mark George, Eric Wasserman, Tim Kimbrell, }ohn Little, Wendol Williams,
Aimee Danielson, Benjamin Greenberg, Mark Hallett, and Robert Post, Mood Im-
provement fllowing Daily Le6 Prehontal Repetitive Transcranial Magnetic Stimu-
lation in Patients with Depression. A Placebo Controlled Crossover Trial,' Amcr/can
)curna| c{ Psycb/a|ry : :;). :;z-6.
:. A. Pascual-Leone, B. Rubio, Pallardo, and M. D. Catala, Benencial Enect
of Rapid-Rate Transcranial Magnetic Stimulation of the Le6 Dorsolateral Prehon-
tal Cortex in Drug-Resistant Depression,' Iancc| | :6). z -;, and Charles
Epstein, Gary Figiel, William McDonald, }ody Amazon-Leece, and Linda Figiel,
Rapid Rate Transcranial Magnetic Stimulation in Young and Middle- Aged Rehac-
tory Depressed Patients,' Psycb/a|r/c Anna|s z :). -.
iLS L PLS 1l]-11 M 2,1
:. A. }. Rush, M. S. George, H. A. Sackeim, L. B. Marangell, M. M. Husain,
C. Giller, Z. Nahas, S. Haines, R. K. Simpson }r. , and R. Goodman, Vagus Nerve
Stimulation VNS) fr Treatment-Resistant Depressions. A Multicenter Study,' /c-
|cy/ca| Psycb/a|ry ;, no. zooo ) . z;6-86.
:. L. B. Marangell, A. }. Rush, M. S. George, H. A. Sackeim, C. R. }ohnson,
M. M. Husain, Z. Nahas, and S. H. Lisanby, Vagus Nerve Stimulation VNS) fr
Major Depressive Episodes. One Year Outcomes,' /c|cy/ca| Psycb/a|ry :, no.
zooz) . z8o-8;.
1. }an Scott, Psychotherapy fr Bipolar Disorder,' r/|/sb )curna| c{ Psycb/a|ry
:6; :). 8:-88.
z. Nick Kanas, Group Psychotherapy with Bipolar Patients. A Revew and Syn-
thesis,' In|crna|/cna| )curna| c{ Crcu Psycbc|bcray :). z:-.
. L. E. Pollack, Content Analysis of Groups fr Inpatients with Bipolar Disor-
der,' A|/cd Nurs/ny Rcscarcb 6 :). :-z;.
. D. Miklowitz, }. Price, E. Holmes, }. Rendell, S. Bell, K. Budge, }. Christensen,
}. Wallace, }. Simon, N. Armstrong, L. McPeake, G. Goodwin, and }. Geddes, Fa-
cilitated Integrated Mood Management fr Adults with Bipolar Disorder,' /c|ar
D/scrdcr :, no. z zo:z). :8-;.
. Beck originally called CBT simply cognitive therapy' Psychologist Donald
Meichenbaum, who has written exensively on Beck's cognitive therapy as well as
on other types of therapy that use the techniques of behavioral psychology to help
change thinking patterns cognition) , is perhaps most responsible fr creating the
broader category we now call cognitive-behavoral therapy' See Donald Meichen-
baum and Roy Cameron, Cognitive-Behavor Terapy' in Ccn|cmcrary cbav/cr
1cray. Ccncc|/cna| and Em/r/ca| Icunda|/cns, ed. G. Terence Wilson and Cyril
M. Franks New York. Guilfrd Press, :8z), :o-;. Althoug some researchers and
theoreticians will describe subtle dinerences between the terms ccy/|/vc |bcray
and ccyn/|/vc-|cbav/cra| 0cra they now seem to be used interchangeably by most
clinical psychologists and by researchers as well.
6. Te area of comparison studies of psychotherapy and medication in the treat-
ment of depression can be accurately described as a hornet's nest of controversy. It's
not dimcult to nnd a study to support any possible view. superiority of medication
over psychotherapy, superiority of psychotherapy over medication, and equal em-
cacy fr both. A nicely designed and well-executed study that fund cognitive ther-
apy to be as helpml as imipramine fr :o; patients with major depressive disorder
is Steven Hollon, Robert DeRubeis, Mark Evans, Marlin Wiemer, Michael Garvey,
William Grove, and Vincente Tuason, Cognitive Terapy and Pharmacotherapy fr
Depression, Singly and in Combination,' Arcb/vcs c{ Ccncra| Psycb/a|ry :z).
;;-8:. Readers who would like to jump into the hornet's nest feet nrst are referred
to }acqueline Persons, Michael Tase, and Paul Crits- Chistoph, Te Role of Psy-
chotherapy in the Treatment of Depression. Review of Two Practice Guidelines,'
Arcb/vcs c{ Ccncra| Psycb/a|ry :6). z8-o, and to the fur yes, fur) accom-
panying rebuttal-commentary articles in the same issue of Arcb/vcs.
2,2 M iLS L PLS 1l-1
;. A. T. Beck, A. }. Rush, B. Shaw, and G. Emory, Ccyn/|/vc 1cray c{ Dcrcs-
s/cn New York. Guilfrd Press, :;) , ::.
8. Te linguistic purist in me wants the plural of scbcma to be scbcma|a or per-
haps scbcmac. But scbcmas is the plural used in cognitive-therapy literature.
. See }an Scott, Cognitive Terapy of Anective Disorders. A Revew,' )curna|
c{ A_cc|/vc D/scrdcrs ; :6). :-::.
:o. David }. Miklowitz, Psychotherapy in Combination with Drug Treatment
fr Bipolar Disorder,' )curna| c{ C|/n/ca| Psycbc barmacc|cyy :6, suppl. :6). 6S-
::. E. Frank, S. Hlastala, A. Ritenour, P. Houck, X. M. Tu, T. H. Monk, A. G. Mal-
linger, and D. }. Kupfer, Inducing Lifestyle Regularity in Recovering Bipolar Disor-
der Patients. Results hom the Maintenance Terapies in Bipolar Disorder Protocol,'
/c|cy/ca| Psycb/a|ry : :;). ::6-
:z. Kay Redneld }amison, An |nqu/c| M/nd. A Mcmc/r c{ Mccds and Madncss
New York. Vintage Books, :6), 88-8.
1 . Te word cm/r/ca| is derived hom the Greek word cmc/r//cs, which means
a doctor relyng on experience alone''
z. C. Bowden, R. Perlis, M. Tase, T. Ketter, M. Ostacher, }. Calabrese, N. Reilly-
Harrington, }. Gonzaliz, N Singh, A. Neirenberg, and G. Sachs, Aims and Results
of the NIMH Systematic Treatment Enhancement Program fr Bipolar Disorder
STEP-BD),' CNS Ncurcsc/cncc and 1cracu|/cs :8, no. zo:z). z-.
1 . Barbara Geller, Kai Sun, Betsy Zimerman, }oan Luby, }eanne Frazier, and
Marlene Williams, Complex and Rapid- Cycling in Bipolar Children and Adoles-
cents. A Preliminary Study,' )curna| c{ A_cc|/vc D/scrdcrs :). z-68.
z. Roselind Neuman, Barbara Geller, }ohn Rice, and Richard Todd, Increased
Prevalence and Earlier Onset of Mood Disorders among Relatives of Prepubertal
versus Adult Probands,' )curna| c{ 0c Amcr/can Acadcmy c{ Cb/|d and Adc|csccn|
Psycb/a|ry 6 :;). 66-
. American Academy of Child and Adolescent Psychiatry, Practice Param-
eters fr the Assessment and Treatment of Children and Adolescents with Bipolar
Disorder,' )curna| c{ |bc Amcr/can Acadcmy c{ Cb/|d and Adc|csccn| Psycb/a|ry 6
:;). :8-;, studies cited on :o.
. See Barbara Geller and }oan Luby, Child and Adolescent Bipolar Disorder.
Revew of the Past Ten Years,' )curna| c{ |bc Amcr/can Acadcmy c{ Cb/|d and Adc|cs-
ccn| Psycb/a|ry 6 :;). ::68-;6.
. Geller, Sun, Zimerman, Luby, Frazier, and Williams, Complex and Rapid-
Cycing in Bipolar Children and Adolescents''
6. M. Strober and G. Carlson, Bipolar Illness in Adolescents with Major De-
pression. Clinical, Genetic, and Psychopharmacologic Predictors in a Tree- to
Four-Year Prospective Follow-up Investigation,' Arcb/vcs c{ Ccncra| Psycb/a|ry ,
no. :8z). -.
iLS L PLS 1-1q M 2,j
;. T. Spencer, }. Biederman, and T. Wilens, Attention-Dencit/Hyperactivity Dis-
order and Comorbidity,' Pcd/a|r/c C|/n/cs c{ Ncr|b Amcr/ca 6, no. :) . :-z;.
8. }. Biederman, S. Faraone, E. Mick, }. Wozniac, L. Chen, C. Ouellette, A. Marrs,
}. Garcia, D. Mennin, and E. Lelon, Attention-Dencit Hyperactivity Disorder and
}uvenile Mania. An Overlooked Comorbidityr" )curna| c{ |bc Amcr/can Acadcmy c{
Cb/|d and Adc|csccn| Psycb/a|ry , no. 8 :6). ;-:oo8.
. S. N Faraone, }. Biederman, D. Mennin, }. Wozniak, and T. Spencer, At-
tention-Dencit Hyperactivty Disorder with Bipolar Disorder. A Familial Subtyper"
)curna| c{ |bc Amcr/can Acadcmy c{ Cb/|d and Adc|csccn| Psycb/a|ry 6, no. :o :; ).
:o. See American Academy of Child and Adolescent Psychiatry, Practice Pa-
rameters fr the Assessment and Treatment of Children and Adolescents'
::. M. Strober, M. DeAntonio, S. Schmidt-Lackner, R. Freeman, C. Lampert,
and }. Diamond, Early Childhood Attention Dencit Hyperactivty Disorder Pre-
dicts Poorer Response to Acute Lithium Terapy in Adolescent Mania,' )curna| c{
A_cc|/vc D/scrdcrs :, no. z :8) . :-:.
:z. T. A. Henderson, Mania Induction Associated with Atomoxetine,' )curna|
c{ C|/n/ca| Psycbc barmacc|cyy z, no. zoo). 6;-68.
:. T. Spencer and }. Biederman, Non-Stimulant Treatment fr Attention-Den-
cit/Hyperactivty Disorder,' )curna| c{ A||cn|/cn D/scrdcrs 6, suppl. : zooz) . S:o-
:. M. Strober, S. Schmidt-Lackner, R. Freeman, S. Bower, C. Lampert, and
M. DeAntonio, Recovery and Relapse in Adolescents with Bipolar Anective Illness.
A Five-Year Naturalistic, Prospective Follow-up,' )curna| c{ |bc Amcr/can Acadcmy
c{ Cb/|d and Adc|csccn| Psycb/a|ry :). ;z-:.
1 . Ellen Leibenlu6, Women with Bipolar Illness. Clinical and Research Issues,'
Amcr/can )curna| c{ Psycb/a|ry : :6). :6 -;.
z. Ibid. , :6.
. K. Yonkers, S. Vigod, and L. Ross, Diagnosis, Pathophysiology, and Man-
agement of Mood Disorders in Pregnant and Postpartum Women,' O|s|c|r/cs and
Cynccc|cg ::;, no. zo::). 6:-;;.
. Ibid. , 6:
. }. Payne, D. MacKinnon, Mondimore, M. McGinnis, B. Schweitzer, R. Zam-
oiski, McMahon, }. Nurnberger, }. Rice, Y Sche6ner, Y Coryell, Y Berrittini,
}. Kelsoe, Y Byerley, E. Gershon, }. DePaulo, and }. Potash, Familial Aggregation
of Postpartum Mood Symptoms in Bipolar Disorder Pedigrees,' /c|ar D/scrdcr :o,
no. : zoo8) . 8-.
6. K. Yonkers, K. Wisner, Z. Stowe, E. Leibenlu6, L. Cohen, L. Miller, R. Manber,
A. Viguera, and T. Suppes, Management of Bipolar Disorder during Pregnancy and
the Postpartum Period,' Amcr/can )curna| c{ Psycb/a|ry 6o, no. : zoo). 6o8-zo.
;. }. Moore, P. Aggarwal, Lamotrigine Use in Pregnancy,' Excr| O/n/cns /n
Pbarmacc0cray :, no. 8 zo:z). :z:-:6, A. Einarson and R. Boskovic, Use and
2,q M iLS L PLS 1q-1) 1
Safety of Antipsychotic Drugs during Pregnancy,' )curna| c{ Psycb/a|r/c Prac|/cc :,
no. zoo ) . :-z.
. Douglas Maskall, Raymond Lam, Shala Misri, Lakshmi Yatham, and Atha-
nasios Zis, Seasonality of Symptoms in Women with Late Luteal Phase Dysphoric
Disorder,' Amcr/can )curna| c{ Psycb/a|ry :| :;). :|-|:.
1. D. A. Reger, M. E. Farm, and D. S. Rae, Comorbidity of Mental Disorders
with Alcohol and Other Drug Abuse. Results hom the Epidemiologic Catchment
Area Study,' )curna| c{ 0c Amcr/can Mcd/ca| Asscc/a|/cn z| :o ). z::-:.
z. Results quoted in Kathleen Brady and Susan Sonne, Te Relationship be-
tween Substance Abuse and Bipolar Disorder,' )curna| c{ C|/n/ca| Psycb/a|ry ,
suppl. :). :-z|.
. Susan Sonne, Kathleen Brady, and Y Alexander Morton, Substance Abuse
and Bipolar Anective Disorder,' )curna| c{ Ncrvcus and Mcn|a| D/scasc :z :|).
|. Markus Henriksson, Hillev Aro, Mauri Marttunnen, Martti Heikkinen,
Erkki Isometsa, Kimmo Kuoppasalmi, and }ouko Lnnqvst, Mental Disorders and
Comorbidity in Suicide,' Amcr/can )curna| c{ Psycb/a|ry :o :). -|o.
. }. Prochaska and Y Velicer, Te Transtheoretical Model of Health Behavior
Change,' Amcr/can )curna| c{ Hca||b Prcmc|/cn :z, no. : :;). -|.
1. A. } . Lewy, H. A. Kern, N. E. Rosenthal, and T. A. Wehr, Brigt Artincial
Light Treatment of a Manic-Depressive Patient with a Seasonal Mood Cycle,' Amcr-
/can )curna| c{ Psycb/a|ry : :z). :|-.
z. Emil Kraepelin, Man/c-Dcrcss/vc Insan/|y and Paranc/a, trans. R. M. Barclay,
ed. G. M. Robertson :z:, reprint, New York. Arno Press, :;), :.
. Norman E. Rosenthal, W/n|cr |ucs. Scascna| A_cc|/vc D/scrdcr Wa| I| Is
and Hcw |c Ovcrccmc I| New York. Guilfrd Press, :), .
|. Ibid. , .
. Diane Boivin, Charles Czeisler, Derk-}an Dijk, }eanne Du, Simon Folkard,
Davd Minors, Peter Totterdell, and }ames Waterhouse, Complex Interaction of the
Sleep-Wake Cycle and Circadian Phase Modulates Mood in Healthy Subjects,' Ar-
cb/vcs c{ Ccncra| Psycb/a|ry | :;). :|-z.
. Michael Terman, Leora Amira, }iuan Terman, and Donald Ross, Predictors
of Response and Non-response to Light Treatment fr Winter Depression,' Amcr/-
can )curna| c{ Psycb/a|ry : :) . :|z-z.
;. Alan L. Kogan and Patricia Guilfrd, Side Enects of Short-Term :o,ooo- Lux
Light Terapy,' Amcr/can )curna| c{ Psycb/a|ry : :) . z-|.
. For an exensive discussion of circadian rhythms and bipolar disorder, see
Frederick K. Goodwin and Kay Redneld }amison, Man/c-Dcrcss/vc I||ncss, znd
ed. New York. Oxford University Press, zoo;), chapter :, Sleep and Circadial
Rhythms,' -.
iLS L PLS 1) -11 M 2,j
. Benedetti, B. Barbini, A. Lucca, E. Campori, C. Colombo, and E. Smeraldi,
Sleep Deprivation Hastens the Antidepressant Action of Fluoxetine,' Eurccan Ar-
cb/vcs c{ Psycb/a|ry and C|/n/ca| Ncurcsc/cncc z|; :;). :oo-:o.
:o. T. Wehr, D. Sack, and N. Rosenthal, Sleep Reduction as a Final Common
Pathway in the Genesis of Mania,' Amcr/can )curna| c{ Psycb/a|ry :|| :;). zo:-|.
1 . Emil Kraepelin, Man/c-Dcrcss/vc Insan/|y and Paranc/a, trans. R. M. Barclay,
ed. G. M. Robertson :z:, reprint, New York. Arno Press, :;), :.
z. M. DelBello and B. Geller, Review of Studies of Child and Adolescent On-
spring of Bipolar Parents,' /c|ar D/scrdcr zoo:). z-|.
1. Robert Sapols|, Wy Zc|ras Dcn`| Cc| ||ccrs, rd ed. New York. Holt Pa-
perbacks, zoo|), ;.
z. C. }. Morales-Medina, Sanchez, G. Flores, Y. Dumont, and R. Quirion,
Morphological Reorganization a6er Repeated Corticosterone Administration in
the Hippocampus, Nucleus Accumbens, and Amygdala,' )curna| c{ Cbcm/ca| Ncurc-
ana|cmy , no. | zoo ). z-;z.
. Lori Altshuler, }ohn Curran, Peter Hauser, }im Mintz, Kirk Denikon, and
Robert Post, Tz Hyperintensities in Bipolar Disorder. Magnetic Resonance Imag-
ing Comparison and Literature Meta- analysis,' Amcr/can )curna| c{ Psycb/a|ry :z
:). ::-||.
|. M. }. Kempton, Z. Salvador, M. R. Munaf, }. R. Geddes, A. Simmons, S. Fran-
gou, and S. C. Williams, Structural Neuroimaging Studies in Major Depressive Dis-
order. Meta-analysis and Comparison with Bipolar Disorder,' Arcb/vcs c{ Ccncra|
Psycb/a|ry zo::). ;-o.
1. Aristotle, attributed by Seneca i n Mcra| Essays, De tranquillitate animi" On
tranquility of mind), sec. :;, subsec. :o, quoted in 1c Cc|um|/a D/c|/cnary c{ Quc-
|a|/cns New York. Columbia University Press, :, CD ROM ed. , :|).
z. Quoted in Kay Redneld }amison, 1cucbcd w/|b I/rc. Man/c-Dcrcss/vc I||ncss
and 0c Ar|/s|/c 1cmcramcn| New York. Free Press, :), zo-.
. Tese studies are described and cited in ibid.
|. Emil Kraepelin, Man/c-Dcrcss/vc Insan/|y and Paranc/a, trans. R. M. Bar-
clay, ed. G. M. Robertson :z:, reprint, New York. Arno Press, :;), :;.
. Quoted in }amison, 1cucbcd w/|b I/rc, :z.
. }ean Cocteau, Le coq et l'arlequin,' i n Ic rac| d |ordrc :z), quoted in
Cc|um|/a D/c|/cnary c{ Quc|a|/cns, CD ROM ed.
;. Tese studies are cited and described in Frederick K. Goodwin and Kay Red-
neld }amison, Man/c-Dcrcss/vc I||ncss, znd ed. New York. Oxford University Press,
zoo;), ;-|:o.
2, M iLS L PLS 1l-l1
1 . Emil Kraepelin, Man/c-Dcrcss/vc Insan/|y and Paranc/a, trans. R. M. Barclay,
ed. G. M. Robertson :z:, reprint, New York. Arno Press, :;6), :;-8:.
z. For a complete discussion of these animal models of the kindling phenome-
non, see Robert Post, Transduction of Psychosocial Stress into the Neurobiology of
Recurrent Anective Disorder,' Amcr/can )curna| c{ Psycb/a|ry : :z). -:o:o.
. Constance Hammen and Michael Gitlin, Stress Reactivty in Bipolar Pa-
tients and Its Relation to Prior History of Disorder,' Amcr/can )curna| c{ Psycb/a|ry
: :;). 86-;.
. T. Treuer and M. Tohen, Predicting the Course and Outcome of Bipolar
Disorder. A Revew,' Eurccan Psycb/a|ry z zo:o ). z8-.
. K. R. }amison, R. H. Gerner, and K. Goodwin, Patient and Physician Atti-
tudes toward Lithium. Relationship to Compliance,' Arcb/vcs c{ Ccncra| Psycb/a|ry
6 :;) . 866-6.
6. Mario Maj, Ranaele Pirozzi, and Lorenza Magliano, Non-response to Re-
instituted Lithium Prophylaxis in Prevously Responsive Bipolar Patients. Preva-
lence and Predictors,' Amcr/can )curna| c{ Psycb/a|ry :z :). :8:o-::. A similar
study concluded that the emcacy oflithium did not diner signincantly" when it was
started a second time in patients who had stopped it. But almost : percent of these
patients needed anc|bcr medication added to the lithium to achieve remission the
second time around. Tis seems to me to indicate that the lithium was nc| as enec-
tive the second time around. ) See Leonardo Tondo, Ross Baldessarini, Gianfranco
Floris, and Nereida Rudas, Enectiveness of Restarting Lithium Treatment a6er Its
Discontinuation in Bipolar I and Bipolar II Patients,' Amcr/can )curna| c{ Psycb/a|ry
: :;). 8-o.
;. Erving Gonman, S|/yma. Nc|cs cn |bc Manaycmcn| c{ Sc/|cd Idcn|/|y Enge-
wood Clins, N}. Prentice-Hall, :6), :, z.
1 . E. C. Harris and B. Barraclough, Suicide as an Outcome fr Mental Disor-
ders. A Meta-analysis,' r/|/sb )curna| c{ Psycb/a|ry :;o :;). zo-z8.
z. See, fr example, }. E. Bailey, A. L. Kellerman, G. Y Somes, }. G. Banton, Ri-
vara, and N. Rushfrth, Risk Factors fr Violent Death of Women in the Home,'
Arcb/vcs c{ In|crna| Mcd/c/nc :; :;). ;;;-8z.
. Amcr/can Hcr/|ayc D/c|/cnary c{ |bc Eny|/sb Ianyuayc, rd ed. New York.
Houghton Mimin, :z) .
1. Kay Redneld }amison, An |nqu/c| M/nd. A Mcmc/r c{ Mccds and Madncss
New York. Vintage Books, :6), :zo.
z. Stephen Strakowski, Susan McElroy, Paul Keck, and Scott West, Suicidality
among Patients with Mixed and Manic Bipolar Disorder,' Amcr/can )curna| c{ Psy-
cb/a|ry : :6). 6;-;6.
iLS L PLS ll1-lq) M 2,,
1 . DISC I i s the name of a gene discovered in :;o that i s now known t o code
fr a protein important fr the growth and development of neurons. Among other
things, this protein is essential fr the growth of axons and dendrites, the nbers that
connect one neuron to others in the nervous system. An abnormal variation mu-
tation) of the gene was nrst identined in a family whose members had an unusually
hig risk of mental illness. Almost half of the family members with the mutation had
schizophrenia, bipolar disorder, major depression, or another psychiatric problem.
Te gene's name comes hom Disrupted ln Schizophrenia' because schizophrenia
was the most common illness in anected family members. Subsequent research has
indicated that DISC I may be important in bipolar disorder as well.
2, M iLS L PL l]l
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0Dd, yy], Ij. Scc a|sc DI0tD
DtOO_y O DtgO0I dt8OIdCI, Iyb2O, DI0tD
HDCltODtD_, 2Oj, hOImODC8, II]Ib, 2O2j,
8lIC88 IC8gOD8C, II]Ib, Iyb2O2, 2OO, 2O1
DtgO0I dt8OIdCI. DtOO_y O, Iyb2O, ChIODO-
DtOO_y 0Dd, 22, IyO, Ibqy2, COuI8C O, 2,
y, I2, IqI, jq, jqj], j, 2I], 22I, CIC0ltVtly
0Dd, IO, 2O]Ij, dCgIC88tVC Cgt8OdC8 tD, 2, y,
20 M 1i1X
I]2, dt0_DO8t8 O, Xtt, I, 2bj, IqyO, dt-
ICDl Im8 O, 2, y, I], tD DSM-, 2, qq, ],
0mty O g0ltCDl Wtlh, 2II, 2jyqy, HluIC
gCI8gCCltVC8 OD, 2I, 2Oj, _CDdCI 0Dd, O,
_CDCltC8 O, qO, IO, Iyjy], ht8lOItC0l gCI-
8gCCltVC8 OD, bb, ltVtD_ Wtlh, 2I, 2I]jO,
m0DtC Cgt8OdC8 tD, 2, yI, mtXCd mOOd
8l0lC8 tD, 2, y, 22], DOl C8CWhCIC C088thCd,
qq, ], gCdt0lItC, Iy, IIb, g0DDtD_ I
CmCI_CDCtC8 tD, 2I, 2jIjb, gICV0lCDCC O, Xt,
2, I0gtd-CyCtD_, 22], qyO, IC0g8C O,
XtXtt, jq, j, j], 22I22 scc a|sc IC0g8C[8)) ,
ICmt88tOD O, jq, j , ]b, IO, I2, 222, Wtlh
8C08OD0 g0llCID, qI, Ib, Ibby, `8OH Im8
O, Xtt, qq], q_ 2, ], yI, Iq, 8l0_C8 O,
IqI, j], 8uD8l0DCC 0Du8C 0Dd, Iy, 8uggOIl
_IOug8 I, Ijj], 22]2b, 2qb, 8ymglOm8
O, I2, , b2], 2I], 2Ib, lIC0lmCDl O, yIb
scc a|sc lIC0lmCDl[8)), tD WOmCD, O, Iy,
DtgOl0I , jOj], j], 0_C 0l OD8Cl O, j2, jj,
dCVClOgmCDl O, j2jq, mOOd Ch0D_C8 tD,
jOj2, j2, D0luI0 ht8lOIy O, jq, jqj], j,
IC0g8C O, XtXtt, jq, j, 22I22, ltmC tDC I
lIC0lmCDl O, I2
DtgOl0I , j]qI, qO, COmg0ICd Wtlh DtgOl0I ,
qOqI, COuI8C O, qO, qI, mOOd Ch0D_C8 tD,
jjy, j, gICV0CDCC O, jy, 8C08OD0 V0It0-
ltOD8 tD, qI
DtgOl0I , qqy, qo
DtgOl0I 8gCClIum dt8OIdCI8, qqqy
DtIlh dCCl8, dIu_-tDduCCd, b, y2, I]I
DtZ0IIC lhtDKtD_DCh0VtOI, b, Ij, I, 2j, OI,
2, IO]b
DOdty IC8gOD8C lO 8lIC88, Iyb2O2, 2OO, 2O1
DOdty Ihylhm8, 22, Iqj, I]j, Ibq, IyI, Iy2. Scc
a|sc ChIODODtOO_y
DOdty 8ymglOm8, 1O, 1o, 222j
DOl0DtC0l8, IIy
DI0tD, ]I], DtgO0I dt8OIdCI 0Dd uDCltODtD_
O, 2Oj, dIu_ 8ltmul0ltOD O ICW0Id CCDlCI8
tD, I]b]y, _CDdCI dtHCICDCC8 tD OI_0DtZ0-
ltOD O, I]O, tm0_tD_ O, 2Oq, 2I, ltmDtC
8y8lCm O, 2O, mCdtC0ltOD CHCCl8 OD, ]q],
mtDd 0Dd, Ijj], mOOd IC_u0ltOD Dy, ,
b, Iyy, 2I, DCuIOlI0D8mtllCI8 tD, ]2, ]j],
gl08ltCtly O, ]j], 8lIC88 CHCCl8 OD, 2OO,
2OO2O2, 2O1
DI0tD IC8C0ICh, 2, 2Oj
DI0tD-8ltmu0ltOD lIC0lmCDl8, I2qjj, II,
2I, dCCg DI0tD 8ltmul0ltOD, Ijj, CCClIO-
CODVul8tVC lhCI0gy, 2, I2qjO, II, I],
lI0D8CI0Dt0 dtICCl CuIICDl 8ltmu0ltOD, Ijj,
lI0D8CI0Dt0 m0_DCltC 8ltmu0ltOD, IjOj2,
II, 2O, 2I, 22, V0_0 DCIVC 8ltmul0ltOD, Ij2
DIC08l-CdtD_, b, Iy, I]2
Tc Brckcn Bra| n [TDdIC08CD), ]I
DugIOgtOD, IO2, 1O2, IO, I]
L0dC, JOhD IJ., q, q,
C0ID0m0ZCgtDC, y2yq, tD gIC_D0DCy, I]I, 8tdC
CHCCl8 O, yq, lhCI0gCultC gIOhlC O, y2yq,
L0l0gIC8. Scc CODtdtDC
C0l0lODt0, 1o, 2, I2
LClCX0. Scc Ctl0OgI0m
LCICllt, \_O, I2
ChCmtC0l tmD00DCC, y]O, ]q, Ij, Iq
ChtdICD. Scc gCdt0lItC DtgOl0I dt8OIdCI
ChlOIdt0ZCgOXtdC, 11
ChlOIgIOm0ZtDC, IO]b, 1O, II, Ij
ChIOmO8OmC8, I, I]b, Iyj, Iyq, Iy, 2I
ChIODODtOlO_y, 22, IyO, Ibqy2, CtIC0dt0D
Ihylhm8, Ibb], 8C08OD0l 0HCCltVC dt8OIdCI,
I], I]j, Ibbby, 8CCg-W0KC CyCC, 22, Ib],
IbyyI, 1O, 22q
LhuIChtl, YtD8lOD, Xt
LtgI0lCX. Scc C8Ctl0lOgI0m
LtgI0mtl. Scc Ctl0lOgI0m
CtIC0dt0D Ihylhm8, Ibb], 8C08OD0 0HCCltVC
dt8OIdCI 0Dd, Ibbby, 8CCg-W0KC CyCC, 22,
Ib], IbyyI, 22q
Ctl0lOgI0m, 1O1
ClOD0ZCg0m, ], 11
ClODtdtDC, I
ClOI0ZCg0lC, 11
ClOZ0gtDC [LlOZ0It), 2, 111, IDI2, Ij, 11j
LOClC0u, JC0D, 2Ij
CO_DtltVC-DCh0VtOI0l lhCI0gy [LD), Ijy
CO_DtltVC CHCCl8, , O dCgIC88tOD, 1o, 2O2I, O
CCClIOCODVu8tVC lhCI0gy, I2]2y, O tlhtum,
b, O m0Dt0, 1O
CO_DtltVC lhCI0gy, Ijyq2, Iqq
COmmtlmCDl, tDVOluDl0Iy, 2jj, 2qqq, 2q]
COmmtlmCDl lO lIC0lmCDl, 2IbIy, 2222j, 2qb
CODHtCl m0D0_CmCDl, Iq2, Iqj, Iqq, 22j2
CODHODltD_ tlDC88, 2I]Iy
CODlI0CCgltOD, I]2]j
COIltCO8lCIOtd8, 2Oj
COIlt8Ol, I, Ib, Iyq, Iyy2OO, 2O2, 2Oj, 22q,
COuD8CtD_, , , ]O, Ijq, Ij], Iq2, Iqj, II, 2Ij,
2jO, DCDChl8 O, Iq, II, Ib, I ChtdICD,
I], I 0mty, Iq2, Iqj, 2qy, gIO88tOD0
lI0tDtD_ I, Iq], 8tlu0ltOD0 8uggOIltVC, Iqq,
tD 8gltl lIC0lmCDl, Iq], I 8lIC88 0Dd CODHtCl
m0D0_CmCDl, 22j2. Scc a|sc g8yChOlhCI0gy
Tc Cracku [tlZ_CI0d), 2I
CIC0ltVtly, IO, 2O]Ij
LItCK, I0DCt8, Iyq
CyClOlhymtC dt8OIdCI, qIqq, q2, mOOd, lhtDK-
tD_, 0Dd DCh0VtOI g0llCID8 tD, qj, mOOd
Ch0D_C8 tD, q1, qIq2, lIC0lmCDl O, I2
LymD0l0. Scc duOXCltDC
0VCd0X. Scc duOXCltDC
dCCg DI0tD 8ltmu0ltOD [Db), Ijj
dCtItum 0HCI ClCClIOCODVu8tVC lhCI0gy, I2]
dCu8tOD8, j], IO], tD DtgO0I , j], tD dCgIC88tOD,
1o, 2j, 2q, 2, I, _I0DdtO8C, IO, I2Ij, hygO-
ChODdIt0C0, 2j, t D m0Dt0, 1O, Ij, I, 2q, I, tD
mtXCd mOOd 8l0lC8, 2, mOOd-COD_IuCDl, O,
tD DCuIO8yghtlt8, I2, g0I0DOtd, 2j2q, I,
O gCI8CCultOD, Ij, O gOVCIly, 2j, ICt_tOu8,
I2Ij, 8ChtZOghICDtC, OI, 2, j
dCmCDlt0 gI0CCOX,
dCDt0l, IbO, 2Ib, 22, 22y, 2j
dCOXyItDODuCCtC 0Ctd [IT) , Iyqy, 2I, 22
Cg0KCDC, Cg0KOlC. Scc V0lgIO0lC
dCgIC88tOD, 2, y, I]2, 2q], T 0Dd,
Iq, 0_tl0lCd, 2, 2Oj, 0lOguItDO I, y],
0DltdCgIC880Dl8 I, ybIO, Ijy, I]b,
0Dltg8yChOltC8 I, IOb, 0lygtC0 0Dltg8yChOl-
tC8 I, I2Ij, tD DtgOl0I , jI, j2, j2, j, j],
tD DtgO0I , jjy, j, qO, qOqI, tD DtgOl0I
8gCClIum dt8OIdCI8, qqqy, q qo, CO_DtltVC
lhCOIy O, IjyqO, CO_DtltVC lhCI0gy I, Iqq,
COIltCO8lCIOtd-tDduCCd, 2Oj, tD CyCOlhymtC
dt8OIdCI, q1, qIq2, q2, dt0_DO8t8 08 D08t8 O
lIC0lmCDl I, I, duI0ltOD O Cgt8OdC8 O,
j, CCClIOCODVul8tVC lhCI0gy I, 2, I2yjO,
tDdtVtdu0 lhCI0gy I, Ijyq2, 0mOlIt_tDC
I, b], m0]OI [CtDtC0), Ib, mtd, Xtt, q2, j,
tD mtXCd mOOd 8l0lC8, 22, 2, `DOIm0,
I]Ib, Iy, tD gCdt0lItC g0ltCDl8, I2, Ijq,
gO8lg0Ilum, I]I, g8CudO-uDtgO0I, q, Wtlh
g8yChOltC 0luIC8, 1o, 2j, 2q, 2, I, Iq, 8C0-
8OD0, Ibb, Ibbby, 8CCg dCgItV0ltOD I,
IyIy2, bl. JOhD8 WOIl I, I222j, 8uD8l0DCC
0Du8C 0Dd, I]y, 8WtlChtD_ DClWCCD m0Dt0
0Dd, j, 8ymglOm8 O, I, I]2, 1o, I, lhy-
IOtd uDCltOD 0Dd, Ib, lI0D8CI0Dt0 m0_DCltC
8ltmu0ltOD I, IjI, uDtgO0I, qO, qb, IjI, I]I,
1i1X M 21
dCQIC88tOD ccn||nucd)
Ibb, Iy, 2O, V0_0 DCIVC 8ltmul0ltOD I, Ij2,
tD WOmCD, I]O, I]I
[DbT), Xtt, ], 2j, 2
dCQIC88tVC 8luQOI, 2q
dC8VCD00XtDC, 1O2
C8yIC. Scc lI0ZOdODC
dt0DClC8 tD8tQtdu8, bq
dt0DClC8 mCltlu8, 0DltQ8yChOltC-tDduCCd, IIjIq
dt0_DO8t8, 2bj, IqyO, 0CCCQl0DCC O, 2I]2O,
O DtQO0I , jOj], O DtQOl0I , j]qI, O
DtQO0I 8QCClIum dt8OIdCI8, qqqy, C088tD-
C0ltOD 8y8lCm I, 2b, O CyClOlhymtC dt8OI-
dCI, qIqq, dCVCOQmCDl O lOO8 I, I2,
dtHCuly O, Xtt, I, dt8CO8uIC O, 222],
Q8yCht0lItC, 2yjO, O I0Qtd-CyCltD_ DtQO0I
dt8OIdCI, qyO, O 8ChtZO0HCCltVC dt8OIdCI,
Oj, lI0um0ltC tmQ0Cl O, Ij], lIC0lmCDl
D08Cd OD, I
D| agncs||c and S|a||s||ca| Manua| c] Mcn|a|
D| scrdcrs (DSM), q], Ibbby, DtQOl0I
C0lC_OItC8 tD DSM-, 2, qq, ], CyCOlhymtC
dt8OIdCI tD, q2, ], ht8lOIy O, q, u8C8 0Dd
tmtl0ltOD8 O, ]
dt0ZCQ0m, q, 11
dtCl, 22q, 0DltQ8yChOltC-tDduCCd WCt_hl _0tD
0Dd, IIjIq, C0HCtDC tD, 22q, NTL tDlCI-
0CltOD8 Wtlh, IOjq, DulItltOD0 8uQQlCmCDl8,
dtH8tOD m0_DCltC IC8OD0DCC tm0_tD_ [dNH),
dt8tDhtDtltOD, II, Ij, qb, I]], 2II, 2j], 2q]
dt8OI_0DtZCd lhtDKtD_ 0Dd DCh0VtOI, Ij, I, I,
IO], IOb, I, 2I2, 2qq
dtuID0 V0It0ltOD O mOOd, 1o, 2I22, Ibb, IyI,
ICVCI8C, Ibb, Iby
dOClOI 0QQOtDlmCDl8, 2IbIy
dOQ0mtDC, 2I, mCdtC0ltOD CHCCl8 OD, y, IO2,
dOuDC-DltDd, Q0CCDO-CODlIOlCd 8ludtC8,
]ybO, b]
dIu_ tDlCI0CltOD8, III, Wtlh l0mOlIt_tDC, b], oo,
Wtlh NTL 8, IOj
dIy mOulh, lItCyCtC 0DltdCQIC880DltDduCCd,
duOXCltDC, IO2, 1O2
dyD0mtC Q8yChOO_y, Ijj
22 M 1i1X
dy8QhOIt0, 2O, 0DltdCQIC880Dl-088OCt0lCd
dy8lODt0, IIO
hItCh, 0u, I
0Vt. Scc 0mtlItQlytDC
dCQIy. Scc 8CC_ttDC
CCClIOCODVu8tVC lhCI0Qy [L), I2qjO, I
DtQO0I dt8OIdCI, 2, I2yjO, II, I],
ht8lOIy O, I2q2, mCmOIy QIODCm8 0HCI,
I2]2y, QIOCCduIC I, I22]
CODVul8tVC lhCI0Qy, I2], 8lCCQ, IyOyI
CmCI_CDCy Q0DDtD_, 2I, 2jIjb, tD8uI0DCC
t88uC8, 2jjjq, 2jj], 80Cly t88uC8 0Dd
hO8Qtl0tZ0ltOD, 2j]jb, 2qq], WhOm lO
C0l I hClQ, 2jqj
CmQOymCDl t88uC8, I], Ijb, 22]
m80m lI0D8dCIm0 8y8lCm. Scc 8CC_ttDC
DdCI, OIm0D, I, Iy, 2I, 22, 2j
CDCI_y CVC, , tD DtQOl0I , q, q], tD dCQIC8-
8tOD, 222j, tD m0Dt0, IO, Ij, I
QtlOl, QuClIO. Scc C0ID0m0ZCQtDC
QtV0. Scc V0lQIO0lC
CIylhCm0 multImC, bb, yq
C8Ctl0lOQI0m, q, 1O1
8K0tlh, 8K0tlh LH. Scc tlhtum
C88CDlt0l lly 0Ctd8, IIy, I2O
CuQhOIt0, yI, 1O
N IOI, y]
CXCICt8C, 22, b, IIq, Iyb, 22q, 22
CXlI0QyI0mtd0 8ymQlOm8 [b), IOyII, IIj
0Ctltl0lCd DlC_I0lCd NOOd N0D0_CmCDl, Ijy
0ICl, JC0D-tCIIC, yO
mtly, 2jyqy, DtQO0I dt8OIdCI IC0Q8C 0Dd,
Iqj, 2qj, 2qb, CItltCt8m O, 2qO, 2qj, CduC0-
ltOD I Q0ltCDl 0Dd, Ijqj, Ijbjy, Iq2qj,
tDlCIVCDltOD8 I, Iq2, Iqj, 2qbqy, tDVO-
uDl0Iy lIC0lmCDl 0Dd lC_0 t88uC8 0HCCltD_,
2qqq, 80Cly t88uC8 0Dd, 2qq], 8uQQOIl
I, 2q]qy, 8ymQlOm ICCO_DtltOD Dy, 2jy
q2, WhOm lO C0l I CmCI_CDCy hClQ, 2jqj
mty ht8lOIy, jO, jI, qO, qq, q O
0D0Ql. Scc tlOQCItdODC
lt_uC, , 1o, 222j, Ibb, IyI
lly 0Ctd8, IIy, I2O
tCVC, HOD0d, ]
D_hl OI Ht_hl IC8QOD8C, Iybyy
DD0DCt0 dCCt8tOD8, II, Iq, I, jOjI, qj
D8h Ot, I2O
tlZ_CI0d, IbCOll, 2I
Ht_hl O tdC08, IO, 2, 2
uOhCX0. Scc HuOXCltDC
HuOXCltDC, ]q, IOO, IOI, 1O1, Iy2
HuVOX0mtDC, 1O1
ICud, bt_muDd, y, 2j, , Ij, IyO
uDCltOD0l tlDC88, j, , y, Ijj
uDCltOD0l m0_DCltC IC8OD0DCC tm0_tD_
[H), 2O
HluIC t88uC8, I]b, 2I, 2Oj
_0D0QCDltD, II]
L0DtlIt. Scc lt0_0DtDC
_0mm0 0mtDODulyItC 0Ctd [LTDT), yO, II]
_08lIOtDlC8ltD0 8tdC CHCCl8. O C0ID0m0ZCQtDC,
yq, O0mOlIt_tDC, bb, O tlhtum, bq, oj, O
bbH8, IOO
_CDCI0l Q0IC8t8 O lhC tD80DC, I2, Ij
_CDC lhCI0Qy, 22
_CDCltC8, qO, IO, Iyjy], tD DtQO0I dt8OIdCI,
Iyy, CDVtIODmCDl0 ClOI8 0Dd, Iy,
_CDC8, ChIOmO8OmC8, 0Dd T, Iyjyq,
_CDCltC dt8C08C8, Iy, tDK8 DClWCCD T
0Dd DtQO0I dt8OIdCI, I, Qh0Im0CO-
_CDOmtC8, 2I2, IC8C0ICh tD, Iyy], 2Ij
Ll0dCm. Scc 8CIlI0ltDC
_lul0m0lC, ], b
_lul0lhtODC, y, I2I
LOHm0D, IVtD_, 22y
_I0DdtO8tly, 1O, I2Ij, Iq, I, I, O, 2, Ij
_IOuQ Q8yChOlhCI0Qy, Ijbjy
_u0DCtDC, I
_u0Idt0D8htQ, 2q
_utly CtD_8, , 1o, Iy, 2j, jb, qI, 2qO, 2qb
h0tI O88, V0QIO0lC-tDduCCd, yI
0dO. Scc h0OQCItdO
h0uCtD0ltOD8, j IO], IOb, tD dCQIC88tOD,
1o, 2q, I, tD m0Dt0, 1O, Ij, I, 2q, I,
mOOd-COD_IuCDl, O, tD DCuIO8yQhtlt8, I,
8ChtZOQhICDtC, OI, j
h0OQCItdO, 1O, II
0DdC, LCOI_C ItdCItC, Xt
h0QQtDC88, , b, Iq, 2O, jb, Iq, Ib2, 2II, 2I, 22b
hC0d0ChC. tD dCQIC88tOD, 1o, 22, jb, dIu_-
tDduCCd, bb, IOO, QhOlOlhCI0Qy-tDduCCd, Iby
hC0llh m0tDlCD0DCC OI_0DtZ0ltOD [NL), Iq],
2jj, 2j
CmtD_W0y, IDC8l, I], 2I2
hCID0 QICQ0I0ltOD8, IIy2O, mCl0lODtD, IIy2O,
bl. JOhD8 WOIl, I2I2j
htQQOC0mQu8, ], Iyy2O2, 2OO, 2O1
ht8lOItC0 QCI8QCCltVC8, bb
hOQCC88DC88, I, Iy, 2, q], 2qO, 2qq
hOImODC8, II]Ib, 0dICD0, IIb, Ib, Iyy, 2O2,
2Oj, DtQOl0I dt8OIdCI 0Dd, 2O2j, mC0lODtD,
II], IIy2O, Ib, tD 8lIC88 IC8QOD8C, II]Ib,
Iyb2O2, lhyIOtd, IIb, 2O2j, tD WOmCD, II],
Iy]O, I]2]j
hO8Qtl0ltZ0ltOD, Q8yCht0lItC, jO, jI, qO, 2,
I2j, 2jj, 2j]jb, tD8uI0DCC COVCI0_C I,
2jjjq, 2jj], tDVOuDl0Iy, 2jj, 2qqq,
2q], Q0Ilt0l [d0y), 2j, I 8utCtd0tly, 2j]jb
um0D LCDOmC IOCCl, Iy, 2I
humOI0 lhCOIy, by
hyQCI0CltVtly, Iq, I, 2O, 2, 2, 2qO, tD T,
], I, Ij, Iq, I, Qhy8tOO_tC0 CHCCl8
O, Iyy
hyQCI8OmDt0, 1o, 2I, Ibb, Iby. Scc a|sc 8lCCQ
hyQCIlhyIOtdt8m, IIb, 2O2, 2Oj
hyQOm0Dt0, II], jI, 0DltdCQIC880Dl-tDduCCd,
q, q
/ tD DtQO0I , jy, j, qO, qO, qI, tD
DtQO0I 8QCClIum dt8OIdCI8, qb, COIltCO-
8lCIOtd-tDduCCd, 2Oj, CIC0ltVtly 0Dd, 2I2,
tD CyClOlhymtC dt8OIdCI, q1, qIq2, q2,
ClCClIOCODVu8tVC lhCI0QytDduCCd, I2y,
QhOlOlhCI0Qy-tDduCCd, Iby
hyQOlhyIOtdt8m, IIb, 2O2, 2Oj , tlhtum-tDduCCd,
oq, b
tdC08 O ICICDCC, 2
tOQCItdODC, 111
tmtQI0mtDC, ], b, ]q, yy,
tmQul8tVtly, q], tD T, I, Iq, I
tD8OmDt0, 1o, 2I, 2, I2, I, I, Iy2, 2Oj ,
DCDZOdt0ZCQtDC8 I, II, III], dIu_-
tDduCCd, IOq, Ib, QhOlOlhCI0Qy-tDduCCd,
Iby. Scc a|sc 8lCCQ dt8luID0DCC8
tD8uI0DCC t88uC8, 2jjjq, 2jj]
In|crna|| cna| C|assqca||cn c] D|scascs (ICD ),
DlCID0ltOD0 bOCtCly I DtQOl0I t8OIdCI8, 2]
DlCIDCl IC8OuICC8, 22, 2]
tDlCIQCI8OD0l 0Dd 8OCt0l Ihylhm lhCI0Qy
[bH), Iqj
DVC_0. Scc Q0tQCItdODC
tDVOuDl0Iy lIC0lmCDl, I], 2j2jj, 2qqq, 2q]
tQIODt0Ztd, yb, IO2
tIItl0Dttly, 2qO, 0DltdCQIC880Dl-088OCt0lCd
ChIODtC tIItl0DC dy8QhOIt0, IO, tD DtQO0I
1i1X M 2j
tIItl0Dtltly ccn||nucd)
, q, q], tD CyCOlhymt0, qj , tD m0Dt0, 1O,
Ij, I, I, jO, I2, tD mtXCd mOOd 8l0lC8, 2, tD
QCdt0lItC Q0ltCDl8, Iq
J0mC8, HODCIl, y
J0mt8OD, 0y HCdDCd, Ij, 2, Iqq, 2Oy, 222, 2q
Cl 0_, I2, I ]
C0l8, JOhD, 2I2
KtdDCy CHCCl8 Oltlhtum, j, q
tD8Cy, THCd, ]
I0CQCtD, mt, Ij, Iq, 2I, 2j, 2, 22], 2y,
j, q, 2, j, , I2, IO, II, I, 2II, 22I,
CODCCQl O CyCOlhymt0, qIqj, CODCCQl O
m0DtC-dCQIC88tVC tD80Dtly, I, I2, qI, OI,
uhD, HO0Dd, ], ]q, yy
0mOlIt_tDC [0mtCl0l) , qq, q, y, y, I
DtQO0I dCQIC88tOD, ], dIu_ tDlCI0CltOD8
Wtlh, ], oo, mCCh0Dt8m O 0CltOD O, ],
, tD QIC_D0DCy, I]I, 8tdC CHCCl8 O, y,
bl0DId QIOlOCOl I tDtlt0ltOD O, y, o,
lhCI0QCultC QIODlC O, ], oo, ltmC lO
CtDtC0l CHCCl O, Ij
0lud0. Scc uI08tdODC
C_0l t88uC8, 2qqq
CX0QIO. Scc C8Ctl0OQI0m
tDItum. Scc ChOIdt0ZCQOXtdC
t8lyC IC_ul0ItZ0ltOD, Iqj, Iy2, Iy, 22I,
t_hl lhCI0Qy, II, I, Iy
tmDtC 8y8lCm, 2O
tlhtum [tlhODtd, tlhOD0lC, tlhOl0D8), x,Iq,
2, jO, jI, ]], Ij, I2, Ij, DOOd CVC8
O, jI, I2, o2, I, 2I, I ChtdICD,
I, COmQ0ICd Wtlh 0mOlIt_tDC, ],
COmQt0DCC Wtlh, 2Iy, dt8CODltDu0ltOD O,
O, j, 222, 22j, 2q, CHCCl OD CIC0ltVtly, 2Ij,
h0l-t O, OI, o1, ht8lOItC0 8ludtC8 O,
q, ]]O, ], mCCh0Dt8m O 0CltOD O,
], duItD_ QIC_D0DCy 0Dd DIC08l-CdtD_, ,
, I]I, QICVCDltOD O 8lIC88-tDduCCd DI0tD
d0m0_C Dy, 2O1, 2OI2, QIOQhy0CltC CHCCl
O, ], ], Q8yChOlhCI0Qy 0Dd, Iqq, tD I0Qtd-
CyCtD_ DtQO0I dt8OIdCI, qy, 8tdC CHCCl8 O,
j, oq, lhCI0QCultC QIODlC O, Oj, o1,
lOXtCtly O, ], I
tVtD_ Wtlh DtQO0I dt8OIdCI, 2I, 2I]jO, Dutld-
2q M 1i1X
tD_ 8uQQOIl 8y8lCm, 222, CODHODltD_ 0Dd
0CCCQltD_ tlDC88, 2I]2O, DOl DCCOmtD_ 0
`DtQO0I VtCltm, 22jO, QI0CltCtD_ mOOd
hy_tCDC, 22O2
OI0ZCQ0m, II, 11
OId DyIOD, Xt, 2O], 2Oo
OX0QtDC [OXtl0DC), 1O
udtOmtl. Scc m0QIOlttDC
uI08tdODC, 111
u8lI0. Scc 8CIlI0tDC
uVOX. Scc HuVOX0mtDC
yItC0. Scc QIC_0D0tD
m0_DCltC IC8OD0DCC tm0_tD_ [NH), 2Oq
m0OI lI0DQuttZCI8. Scc 0DltQ8yChOltC
m0D0_Cd C0IC, 2jj]
m0Dt0, 2, yI, V8. T, Ij, Iq, 0Dlt-
Q8yChOltC8 I, IO, tD DtQO0I , jOjI, j2,
j2, j, j], CIC0ltVtly 0Dd, 2I2, dC0yCd lIC0l-
mCDl I, I], dCltItOu8, Iq, 2, duI0ltOD O
CQt8OdC8 O, j, dy8QhOItC, I, 2O, 22, II2,
2q], CCClIOCODVu8tVC lhCI0Qy I, I2yjO,
V8. hyQOm0Dt0, II], CD_lh O ltmC DCIC
hO8Qtl0tZ0ltOD I, 1], mtXCd, 22, mOI-
l0ltly 0Dd, Iq, tD QCdt0lItC Q0ltCDl8, I2, Ij,
QICCtQtl0lCd Dy T mCdtC0ltOD8, I,
QICCtQtl0lCd Dy 0DltdCQIC880Dl8, q_ ], ,
y, IO, Ijy, I], I, QICCtQtl0lCd Dy 8lCCQ
dCQItV0ltOD, Iy2, 22q, V8. 8ChtZOQhICDt0, Iq,
8l0_C8 O, IqI, 8WtlChtD_ DClWCCD dCQIC8-
8tOD 0Dd, j, 8ymQlOm8 O, I2, 1O, IOIq,
uDQC080DlDC88 O, Iq, I
m0DtC-dCQIC88tVC tDC88, y, I]. Scc a|sc DtQO0I
m0Itl0 IC0ltOD8htQ, Ij, Iq2, 22j
mCdtC0 CODdtltOD8, IO, TmCItC0D8 Wtlh t8-
0DttltC8 TCl 0Dd, 22], Q0tDu, 1o, 222j
mCdtC0ltOD8. 0DltdCQIC880Dl8, yIO, IO,
I], 0DltQ8yChOltC8, IO]Iq, IO, Ij, I
0DXtCly 0Dd 8lCCQ dt8luID0DCC8, III], 11,
Ij, I, COmQt0DCC Wtlh, 2IIy, 2222j,
CODlI0CCQltVC, I]2]j, dt8CODltDu0ltOD O,
XtXtt, O, j, I]I, I]2, 222, 2q, duI0ltOD O
lIC0lmCDl Wtlh, I2, 222, 2j, ClCClIOCOD-
Vul8tVC lhCI0Qy 0Dd, I2y, tD8uI0DCC COVCI0_C
I, 2j, m0D0_CmCDl tD 8Qtl lIC0lmCDl, Iq],
mOOd 8l0DttZCI8, qqq, ]]y], -0CCly
Cy8lCtDC, y, I2O2I, OH-0DC QIC8CItDtD_ O,
yy, IIj, 2j, Qh0Im0CO_CDOmtC8, 2I2,
duItD_ QIC_D0DCy 0Dd DIC08l-CdtD_, b,
b, I]I]2, Q8yChOlhCI0Qy 0Dd, Ij, Ij], Iqq,
I IC0Q8C QICVCDltOD, ], ]b, II2, 222, 22j,
ICmtDdCI 8y8lCm8 I, 22j, 8ltmu0Dl8, I,
I, lhCI0QCultC IC8ull8 08 _utdC lO u8C O,
IqbI, ltmC lO CtDtC0 CHCCl O, I2. Scc
a|sc sccqc drugs and c|asscs
NCd8C0QC, 2]
mC0DChOlt0, jb, q, bO
mC0lODtD, II], IIy2O, Ib
NCl0Itl. Scc lhtOItd0ZtDC
mCmOIy QIODCm8, , 1o, 2I, 2y, 0HCI CCClIO-
CODVu8tVC lhCI0Qy, I2]2y
NCDdCl, m0DuC, I
NCDdCl, LIC_OI, Iyjyq
mCD8lIu0ly IC0lCd mOOd HuClu0ltOD8, Iy,
mCDl0 8l0lu8 CX0mtD0ltOD, 2y
NtKOWtlZ, 0Vtd, Ijy
A M| nd Ta| Fund I|sc] [DCCI8), I
mtIl0Z0QtDC, 1O2
mtXCd mOOd 8l0lC8, 2, y, 22], q]
mOtDdODC [NOO0D) , 1O
mODO0mtDC OXtd08C [NTL-T 0Dd NTL-D),
IO2q, IO
mODO0mtDC OXtd08C tDhtDtlOI8 [NTL8), yb,
IO2q, 1Oj
mOOd. 0HCCl 0Dd, y, DI0tD IC_u0ltOD O, , b,
Iyy, 2I, CIC0ltVtly 0Dd, 2I2, dCDDtltOD O, ,
y, dtuID0 V0It0ltOD O, 1o, 2I22, Ibb, Iby,
IyI, _OOd V8. OW, , hOImODC8 0Dd, II]Ib,
mCD8lIu0ly ICl0lCd HuClu0ltOD8 O, Iy,
I]2]j, IC0CltVtly O, Ib, 8C08OD0 Ch0D_C8 tD,
qI, II], I]j, Ib, Ibby
mOOd, 0DDOIm0, 2j, 2], COD8lItClCd mOOd,
IbIy, dCQIC88tOD, I]2, hyQOm0Dt0, II],
m0Dt0, yI, mtXCd 8l0lC8, 2, y, 22], 8ChtZO-
QhICDt0 0Dd, 2
mOOd Ch0Il, Iqj, 22
mOOd hy_tCDC, 22O2
mOOd-8l0DtltZtD_ mCdtC0ltOD8, qqq, ]]y],
IO, Ij, C0ID0m0ZCQtDC, y2yq, I ChtdICD,
I, CHCCl OD CIC0ltVtly, 2Ij, OD lhC hOIt-
ZOD, yy], IO, l0mOlIt_tDC, bby, Ijq,
tlhtum, ]]b, mCCh0Dt8m8 O 0CltOD O, ],
-0CCly Cy8lCtDC, y, OXC0ID0ZCQtDC, yqy,
QI0mtQCXOC, y, duItD_ QIC_D0DCy 0Dd
DIC08l-CdtD_, b, b, I]I]2, ItuZOC, y,
lt0_0DtDC, y, V0QIO0lC, byy2, ZODt80mtdC,
y. Scc a|sc sccqc drugs
-0CCly Cy8lCtDC [TL), y
0Idt. Scc QhCDClZtDC
0ltOD0l Tlt0DCC I lhC NCDl0ly l [TN),
0ltOD0l NCDl0 C0lh T88OCt0ltOD [N),
2jqj, 2]
D0luI0l ht8lOIy, jq, jqj], j
0V0DC. Scc lhtOlhtXCDC
DCuIOtm0_tD_, 2Oq, 2I
DCuIOCQltC8. Scc 0DltQ8yChOltC mCdtC0ltOD8
DCuIOD8, ]2, ]j], 0QOQlO8t8 O, b,
htQQOC0mQ0, ], Iyy2OI, 2OO, 2O1
CuIODltD. Scc _0D0QCDltD
DCuIOQ08ltCtly, ]j]
DCuIOlI0D8mtllCI8, ]O, ]2, ]j], mCdtC0ltOD
CHCCl8 OD, ], yy, IOO, IO2j, IOb
yy, IOO, IO2, IOj
OIQI0mtD. Scc dC8tQI0mtDC
DulItltOD0 8uQQCmCDl8, IIy2O
OH-0DC QIC8CItDtD_, yy, IIj, 2j
O0DZ0QtDC, 111, 11j
OmC_0-j lly 0Ctd8, I2O
Onc F|cw Ovcr |nc Cuckccs Ncs|, I2, I2
OQltmt8m, , , q, qo
OI_0DtC tlDC88, Ij
OIlhO8l0ltC hyQOlCD8tOD, NTL-tDduCCd, IOq
OXtd0ltVC d0m0_C, I2I
Q0tDH CODdtltOD8, 1o, 222j
Q0tQCItdODC, 111
0mCOI. Scc DOIlItQlytDC
Q0DtC 0ll0CK8, 2, Ij, I, ], II], Ij
0ID0lC. Scc lI0DyCyQIOmtDC
Q0ltCDl0mty CduC0ltOD, Ijqj, Ijbjy,
0Xt, 0Xtl LH. Scc Q0IOXCltDC
QCdt0lItC DtQOl0I dt8OIdCI, Iy, IIb, T
0Dd, Ij, Iq, 0_C 0l OD8Cl O, II, COm-
Q0ICd Wtlh 0dul DtQO0I dt8OIdCI, I2, 12,
COuI8C O, II, I], dCQIC88tOD 08 DI8l 8t_D O,
I2, Ijq, dCVCOQmCDl0 CHCCl8 O, I],
HluIC IC8C0ICh tD, I]b, QIO_DO8t8 I, I],
I0Qtd-CyCtD_, II, I2, I, I], 8ymQlOm8 O,
Ijq, lIC0lmCDl O, II, I]
1i1X M 2j
QC88tmt8m, , , 2O, Ijy, 2qO
Qh0Im0CO_CDOmtC8, 2I2
QhCDOlht0ZtDC8, IO]. Scc a|sc 0DltQ8yChOltC
QhOlOQCItOd m0DtQu0ltOD, Ib, Ibb
QhOlOlhCI0Qy, II, Ib, Ibbby
Qhy8tC0 IC8lI0tDl O Q0ltCDl, y, j, 2q]
l0lh, byVt0, 2I2
OC, d_0I Tl0D, Xt
QO8lQ0Ilum mOOd dt8OIdCI8, II], I]O]I
QOWCI O 0llOIDCy, 2q
QI0mtQCXOlC, y
QIC_0D0ltD, II]
tD, I2y, mCdtC0ltOD8 duItD_, b, b, I]I]2
QICmCD8lIu0 8yDdIOmC8, I]2]j
QIC88uICd 8QCCCh, II, I, I, 2
It8ltQ. Scc dC8VCD00XtDC
QIOCI08ltD0ltOD, 22q2
Q8CudO-Q0IKtD8ODt8m, IIO
Q8yCht0lItC C0IC, 2j2j
Q8yCht0lIt8l-Q8yChOlhCI0Qt8l, Iq]
Q8yChO0D0lyltC lIC0lmCDl, j, ]
Q8yChO-CduC0ltOD0 _IOuQ lhCI0Qy, Ijbjy
Q8yChO8t8, IO], 0DltQ8yChOltC8 I, IO]Iq. Scc
a|sc dCu8tOD8, h0uCtD0ltOD8
Q8yChOlhCI0Qy, ]O, Ijqq], II, 2jO, DCDCDl8
tD DtQO0I dt8OIdCI, Ij], Iq, Iqq], Ib,
dyD0mtC, Ijj, Iqq, I mty, Iq2, Iqj,
2qy, _IOuQ, Ijbjy, tDdtVtdu0l lhCI0Qy I
dCQIC88tOD, Ijyq2, mCdtC0ltOD8 0Dd, Ij, Ij],
Iqq, DCW lIC0lmCDl mOdCl8 I, Iq2qj, QIO-
88tOD0 lI0tDtD_ I, Iq, tD 8Qtl lIC0lmCDl,
Iq], I 8lIC88 0Dd CODHtCl m0D0_CmCDl,
22j2, lI0dtltOD0 tDdtVtdu0, Iqqq, lyQC8
O, Ijj]
uDNCd, 2]
QuClt0QtDC, 111, 11j
I0CtD_ lhOu_hl8, 1O, IOII, Ij, Iq, I, IOb, I2
I0Qtd-CyCtD_ DtQO0I dt8OIdCI, qyO, 0Dlt-
dCQIC880Dl8 0Dd, qy, O, yb, IOq, IO, Ijy, I],
tD ChtldICD, II, I2, I, I], hyQOlhyIOtd-
t8m 0Dd, IIb, ulI0-I0QtdCyCtD_, 22], tD
WOmCD, O, Iy]O
I0Qtd CyC mOVCmCDl [HN) 8CCQ, 1O, IyOyI
2 M 1i1X
I08h, dIu_-tDduCCd, bbby, yq
IC0Q8C[8), jq, j, j], 0HCI mCdtC0ltOD dt8COD-
ltDu0ltOD, XtXtt, O, I]I, I]2, 0DltdCQIC880Dl8
0Dd, I], mty 0Dd, Iqj, 2qj, 2qb, tlhtum
DOOd CVC 0Dd, bI, o2, mCdtC0ltOD8 I QIC-
VCDltOD O, II2, 222, 22j, tD QCdt0lItC Q0ltCDl8,
I], duItD_ QIC_D0DCyQO8lQ0Ilum, I]I]2,
Q8yChOlhCI0Qy 0Dd, Ij], Ijb, IqI, Iq2, Iqj, Iqq,
tD 8l0_C8-O-Ch0D_C mOdC, 1o1, Ib2, 8lIC88
0Dd, 22I22, 2qj, 8utCtd0ltly 0Dd, 2j], 2jb
IC0ltOD8htQ QIODCm8, 2O2, 2Ib, 22j, 22, 22b,
2qb, Wtlh CmQOyCI8, 22], O QCdt0lItC Q0-
ltCDl8, I], Q8yChOlhCI0Qy I, Iq2q
HCmCI_t, HCmCIOD. Scc mtIl0Z0QtDC
IC8C0ICh, 2Oj, _CDCltC, Iyy], 2Ij,
DCuIO8CtCDCC, 2, 2Oj, tD QCdt0lItC DtQO0I
dt8OIdCI, I]b
IC8OuICC8, 2]
ItuZOC [HtlulCK), y
It8QCItdODC [Ht8QCId0l), 111, 11j
HO8CDlh0, OIm0D, Ib
80dDC88, , , b, Iq, Iy, 2O, 2], q2, Iqq, Iq, 2II
80Cly t88uC8, 2j]jb, 2qq], CCClIOCODVu8tVC
lhCI0Qy, I2, I2], II, tDVOuDl0Iy lIC0lmCDl
0Dd, 2qqq. Scc a|sc 8utCtd0tly
b0QhIt8. Scc 08CD0QtDC
b0QO8Ky, HODCIl, Iyy
b0I0Cm. Scc HuOXCltDC
8ChtZO0HCCltVC dt8OIdCI, Oj
8ChtZOQhICDt0, b, I, Oj, O, j, 0Dlt-
Q8yChOltC8 I, IO]b
bChOu, NOI_0D8, ], ]bbO, ], b2, 2Ij
bChum0DD, HODCIl, 2Oby, 21O
8COQO0mtDC, y]
bC0dtD. Scc 8CIlI0tDC
8C08OD0 0HCCltVC dt8OIdCI [bT), II], I]j, Ibbby
8C08OD0 mOOd Ch0D_C8, Ibb
8ClCCltVC 8CIOlODtD ICuQl0KC tDhtDtlOI8 [bbH8),
8ClC_ttDC, 1Oj, IOq
bCIOQuC. Scc QuClt0QtDC
8CIOlODtD, ]q, 2I, mCdtC0ltOD CHCCl8 OD, yy,
lOI8 [bH8), IO2, 1O2
8CIlI0tDC, 1O1, I]
8CXu0 DCh0VtOI. tD CyClOlhymt0, qj , tD dCQIC8-
8tOD, 1o, 22, tD hyQOm0Dt0, I, tD m0Dt0, 1O,
II, I2, Iq, O QCdt0lItC Q0ltCDl8, Ij
8CXu0l dy8uDCltOD, dIu_-tDduCCd, IOI, IOq
8h0mC, Iy, jb, 2, Iq, 2qj
btdCItl. Scc lI0ZOdODC
btDCQu0D. Scc dOXCQtD
8KtD CHCCl8 O dIu_8. C0ID0m0ZCQtDC, yq, l0mO-
lIt_tDC, bbby, tlhtum, oq, b
8CCQ dCQItV0ltOD, II, Iqj, I]I, Iby, 2Ib, 22, 2Ib,
m0Dt0 QICCtQtl0lCd Dy, Iy2, 22q, lhCI0QCultC,
Iby, IyIy2
8CCQ dt8luID0DCC8, , tD CyClOlhymtC dt8OI-
dCI, qj, tD dCQIC88tOD, 2I22, qO, IyIy2, tD
m0Dt0, 1O, I2, mCdtC0ltOD8 I, III], 1, Ij,
I, tD mtXCd mOOd 8l0lC8, 2, tD 8C08OD0l
0HCCltVC dt8OIdCI, Ibb, Iby
8CCQ-W0KC CyCC, 22, Ib], IbyyI, 1O, 22q
8OW-W0VC 8lCCQ [bYb), 1O, IyOyI
8OCt0 Ihylhm mClItC, Iqj
8OCt0l WtlhdI0W0l, 1o, 2Oj
8QCDdtD_ 8QICC8, II, Iq, jO, qj
8Qtl lIC0lmCDl, Iq]
8l0_C8-O-Ch0D_C mOdC, IbObj, 1o1
blC0ZtDC. Scc lItHuOQCI0ZtDC
blCVCD8-JOhD8OD 8yDdIOmC, yq
8lt_m0, 22y
8ltmul0Dl8, I, I
bl. JOhD8 WOIl, I2I2j
8lOCKl0KtD_, 22q
blI0llCI0. Scc 0lOmOXCltDC
8lIC88, Iq2qj, 2Ib, DOdty IC8QOD8C lO, II]Ib,
Iyb2O2, 2OO, 2O1, m0D0_CmCDl O, Iq2, Iqj,
22I, 22j2q, DCuIOQ08ltCtly 0Dd, ], ICl0Q8C
0Dd, 22I22, 2qj
8luQOI, dCQIC88tVC, 2q
blyIOD, Ytt0m, Iy, 2O, 22, 2q
8uD8l0DCC 0Du8C0ddtCltOD, II, I2, qj, q, Iy,
I]qbj, DtQO0I DtD_C8 0Dd, I]q]], DI0tD
CHCCl8 O, I]b]y, IC0ltOD8htQ DClWCCD
DtQO0I dt8OIdCI 0Dd, I]b, 8l0_C8-O-Ch0D_C
mOdCl 0Dd lIC0lmCDl O, IbObj, 1o1, 8utCtdC
0Dd, I]ybO
8utCtd0ltly, Xtt, 1o, 2q, 2, jI, qI, q], I, 2I2, 2qq],
CCClIOCODVu8tVC lhCI0Qy I, I2y, hO8Qtl0tZ0-
ltOD I, 2j]jb, 2q], QICVCDltOD O, 2j], It8K
ClOI8 I, 2q], 8uD8l0DCC 0Du8C 0Dd, I]ybO
8uQQOIl _IOuQ8, Ijj], 22]2b, 2jO, 2qb
8uQQOIl 8y8lCm, 222b, I mty, 2q]qy
8ymQlOm8, I2, , by, 2I], 2Ib, O dCQIC88tOD,
I]2, mty ICCO_DtltOD O, 2jyq2, O
hyQOm0Dt0, II], O m0Dt0, I2, yI, I2, tD
QCdt0lItC Q0ltCDl8, Ijq, ICmt88tOD O, jq,
j, ]b, IO, I2, 222, 8C08OD0 V0It0ltOD tD, qI,
II], I]j, Ib, Ibby, tD WOmCD, Iy]O
8yD0Q8C8, ]2, ]j]q
byDlhyIOtd. Scc CVOlhyIOXtDC
8yQhtlt8, I2, I2, Ij
by8lCm0ltC IC0lmCDl Dh0DCCmCDl IO_I0m
I DtQO0I t8OIdCI [b-D), IOq,
II2, I]b
l0CItDC, I
`l0KtD_ CuIC, 2, ]. Scc a|sc Q8yChOlhCI0Qy
l0IdtVC dy8KtDC8t0 [), IIO
lCmQCI0mCDl, q2, DtQO0I 8QCClIum dt8-
OIdCI8 0Dd, q, q], CyClOlhymtC, qIq2,
hyQCIlhymtC, q], qo
CDCX. Scc _u0DCtDC
lC8lO8lCIODC, I]O, Iyq
lhtDKtD_ Q0llCID8. tD CyCOlhymtC dt8OIdCI, qj ,
tD dCQIC88tOD, Ib, 2O2I, tD m0Dt0, IOIq, 2
lhtOItd0ZtDC, 1O
lhtOlhtXCDC, 1O
lhyIOtd dt8OIdCI8, qy, 2O2j, 2Oj, ltlhtum-
tDduCCd, oq, b
lhyIOtd hOImODC8, IIb, 2O2j
lt0_0DtDC, y
OH0Dt. Scc tmtQI0mtDC
lOXtC CQtdCIm0 DCCIO8t8, bbby
lI0D8CI0Dt0 dtICCl CuIICDl 8ltmu0ltOD [lLb),
lI0D8CI0Dt0 m0_DCltC 8ltmu0ltOD [Nb),
IjOj2, II, 2O, 2I, 22
lI0DyCyQIOmtDC, 1Oj
lI0ZOdODC, 1O2
lIC0lmCDl[8). 0l_OItlhm8 I, II, 0DltdCQIC8-
80Dl8, ybIO, IO, 0DltQ8yChOltC mCdtC0-
ltOD8, IO]Iq, IO, I 0DXtCly 0Dd 8CCQ
dt8luID0DCC8, III], 1, DI0tD-8ltmu0ltOD
lCChDtQuC8, I2qjj, II, 2O, 2I, COuD8CltD_
Q8yChOlhCI0Qy, Ijqq], II, Ib, duI0ltOD
O, I2, 222, 2j, _CDCltC IC8C0ICh 0Dd,
Iyy], 2Ij, hCID0l QICQ0I0ltOD8 0Dd
DulItltOD0 8uQQlCmCDl8, IIy2O, ht8lOItC0,
jb, tDVOuDl0Iy, I], 2j2jj, 2qqq, 2q],
mOOd-8l0DttZtD_ mCdtC0ltOD8, qqq, ]]y],
IO, OmC_0-j lly 0Ctd8 0Dd D8h Ot, I2O,
Q0ltCDl COmmtlmCDl lO, 2IbIy, 2222j, 2qb,
I QCdt0lItC Q0ltCDl8, II, I], QhOlO-
lhCI0Qy, II, Ib, Ibbby, ICH80l O, 2qb, 8CCQ
dCQItV0ltOD, Iby, IyIy2, b-D 8ludy O,
IOq, II2, I]b, I 8uD8l0DCC 0Du8C
1i1X M 2,
lIC0lmCDl[8) ccn||nucd)
0ddtCltOD, IbObj, 1o1, 8ymQlOm0ltC, II,
I2y, I, I, lhCI0QCultC IC8ul8 08 _utdC lO,
IqbI, lhyIOtd hOImODC8, IIb
lICmOI, dIu_-tDduCCd, oq, bqb, yI
lItCyCtC 0DltdCQIC880Dl8, ybIOO,
yCDO. Scc 0CCl0mtDOQhCD
ullI0-I0QtdCyCltD_ DtQOl0I dt8OIdCI, 22]
ulttZ0ltOD ICVtCW, 2j
V0_0 DCIVC 8ltmul0ltOD [Nb), Ij2
N0ltum. Scc dt0ZCQ0m
V0lQIO0lC, byy2, y, Ij, DOOd CVC8 O, yI,
2Ib, I ChtdICD, I, ht8lOItC0l 8ludtC8 O,
byyO, mCCh0Dt8m O 0CltOD O, yO, tD QIC_-
D0DCy, I]I, 8tdC CHCCl8 O, yIy2, lhCI0QCultC
QIODlC O, yOyI, 1
V0D LO_h, NtDCCDl, Xt, 2O]b, 2I2, 2Ij
VCD00XtDC, IO2, 1O2
Vt0ZOdODC [NttDIyd), 1O2
VtOlCDl DCh0VtOI, Ij, Iq, I, I, 2I2, 2q, 2q]
Vtl0mtD8, IIy
NtV0Clt. Scc QIOlItQlytDC
VOD NCduD0, JO8CQh 0dt8l08, I2q2
Y088CIm0DD lC8l I 8yQhtt8, I, I2
Y0l8OD, J0mC8, Iyq
2 M 1i1X
YCDN, 2]
WCt_hl Ch0D_C8. tD DtQOl0I dt8OIdCI, I2, 1o,
22, jI, tD hyQOlhyIOtdt8m, IIb, tD 8C08OD0l
0HCCltVC dt8OIdCI, Ibb, Iby
WCt_hl Ch0D_C8, dIu_-tDduCCd. 0lyQtC0 0Dlt-
Q8yChOltC8, 11j, IIjIq, tlhtum, oq, b,
NTL 8, IOq, bbH8, IOI, lItCyCltC 0DltdCQIC8-
80Dl8, 1OO, V0lQIO0lC, yI
WCl-DCtD_, , y, 2O, b, 22O
YClDulItD, YClDulItD bH, YClDulItD 7. Scc
WOmCD Wtlh DtQO0I dt8OIdCI, Iy, Iy]j, QO8l-
Q0Ilum mOOd dt8OIdCI8 0Dd 0mtly Q0DDtD_
I, I]O]2, QICmCD8lIu0l 8yDdIOmC8 tD,
I]2]j, I0Qtd CyCtD_ tD, O, Iy]O, 8ymQ-
lOm dtHCICDCC8 tD, Iy]O
YOO, NtI_tDt0, Xt
YOId C0llh LI_0DtZ0ltOD, , II
WOIlhC88DC88, Iy, IqI, 2qO
70D0X. Scc 0QI0ZO0m
7CIt8l0I. Scc duOXCltDC
3CDlICVC. Scc dulOXCltDC
Z0CltD. Scc lluOXCltDC
ZtQI08tdODC, 111, 11j
Zt8QtD. Scc mtIl0Z0QtDC
ZOOH. Scc 8CIlI0ltDC
ZODt80mtdC [ZODC_I0D), y
ZyQICX0, ZyQICX0 Zydt8. Scc Ol0DZ0QtDC