REVISTA ROMN DE PEDIATRIE VOLUMUL LXI, NR.

2, AN 2012 130
Adresa de coresponden:
Asist. Univ. Dr. Anamaria Burlea, Universitatea de Medicin i Farmacie Gr. T. Popa, Str. Universitii Nr. 16, Iai
e-mail: anamburlea@yahoo.com
PARTICULARITI CLINICO-EVOLUTIVE I
TERAPEUTICE ALE TULBURRILOR AFECTIVE
BIPOLARE LA COPII I ADOLESCENI
Asist. Univ. Dr. Alexandra Bolo, Asist. Univ. Dr. Anamaria Burlea,
Prof. Dr. Roxana Chiri
Universitatea de Medicin i Farmacie Gr. T. Popa, Iai
REZUMAT
Tulburrile afective bipolare reprezint o condiie medical nc subdiagnosticat sau nediagnosticat la
copii i adolesceni. Trsturile clinice specice, cum ar ciclarea rapid i episoadele mixte, complic, de
obicei, posibilitile de diagnostic clinic. n plus, comorbiditile asociate sau supraadugate pot avea impact
asupra diagnosticului diferenial. Astfel, vor necesare studii specice diferitelor grupe de vrst care vor
genera criterii de diagnostic particulare ecrei vrste. Acest lucru este necesar pentru tinerii pacieni
deoarece un diagnostic adecvat ct mai precoce va determina i un management terapeutic adecvat.
Cuvinte cheie: tulburare afectiv, diagnostic, adolesceni, terapie
REFERATE GENERALE
3
Tulburrile psihice ale copiilor sunt mult mai
dicil de caracterizat dect cele ale adulilor. Dei
s-au realizat progrese n ceea ce privete diagnosticul
tulburrilor psihice la copii, multe tratamente sunt
administrate pentru o simptomatologie vag, cum
ar agresivitate, depresie sau manifestri discom-
por tamentale (1). O serie de factori contribuie la
aceast situaie, cum ar :
mult timp copiii au fost neglijai de serviciile
medicale psihiatrice;
conceptul de anormalitate la copii este in u-
enat de procesul de dezvoltare a acestora,
ceea ce face mult mai dicil interpretarea
unor indicatori ai disfuncionaliti cere brale;
diagnosticul diferenial este mult mai dicil
de realizat la copii comparativ cu adulii, din
cauza lipsei expresivitii modicrilor com-
portamentale din psihopatologia copiilor;
copiii prezint multe diculti n ceea ce
privete descrierea simptomatologiei psihia-
trice.
Debutul simptomatologiei tulburrilor afective
bipolare se realizeaz la vrste foarte diferite, n
special ntre 18 i 24 de ani, dar 59% dintre adulii
bipolari au prezentat un prim episod afectiv naintea
vrstei de 18 ani. Simptomatologia speci c
tulburrilor afective bipolare este variabil la copii
i adolesceni i prezint o serie de simptome supra-
adugate i comorbiditi, cum ar abuzul de dro-
guri sau ADHD. Astfel, se constat c la un numr
important de copii tulburarea afectiv bi polar este
greit diagnosticat; de aceea, se ncearc gsirea
unei soluii n ceea ce privete diagnosticarea pre-
coce a acestei tulburri psihice pentru a asigura un
tratament adecvat. Diagnosticarea ct mai pre coce
a tulburrii afective bipolare reprezint un obiectiv
clinic important, avndu-se n vedere ur m toarele
motive (4):
tulburarea afectiv bipolar reprezint o surs
important de disfuncionalitate psihosocial
pentru copii i adolesceni, cu importante
con secine asupra vieii acestora;
exist evidene clinice care arat faptul c un
sindrom psihiatric, cu ct este mai prelungit,
cu att acesta este mai refractar la tratament.
Un diagnostic precoce al tulburrii afective bi-
polare la copii i adolesceni este asigurat de o serie
de factori, i anume (5):
REVISTA ROMN DE PEDIATRIE VOLUMUL LXI, NR. 2, AN 2012 131
Identicarea simptomelor sugestive pentru
episodul maniacal;
Cnd nu exist simptome psihotice, se va
asigura un diagnostic diferenial adecvat ntre
manie i ADHD;
Cnd exist simptome psihotice, diagnosticul
diferenial se va realiza ntre manie i schi-
zofrenie.
Estimarea prevalenei tulburrilor afective la
copii i adolesceni este foarte dicil deoarece
exist foarte puine studii pe acest tip de populaie.
n trecut, se considera c tulburrile afective bi-
polare ar rar ntlnite la copii i adolesceni, dar
n prezent se tie faptul c aceast tulburare psihic
este frecvent, prevalena sa ind nc necu noscut
(6). Rata prevalenei depinde de criteriile de
diagnostic utilizate. DSM IV prezint aceleai
criterii de diagnostic pentru toate tipurile de pacieni
cu tulburare afectiv bipolar, indiferent de vrst
(7). Cu toate acestea, clinicienii trebuie s ia n con-
siderare toate aspectele referitoare la dezvoltarea
co respunztoare a copiilor i adolescenilor, atunci
cnd acetia sunt evaluai din punct de vedere psi-
hiatric. De aceea, este important s nelegem
aceast tulburare psihic din punct de vedere al
dezvoltrii i creterii adecvate a acestora. De
exemplu, unii tineri care prezint ciclare rapid a
episoadelor sau episoade hipomaniacale nu nde-
plinesc criteriile de diagnostic pentru tulburarea
afectiv bipolar a adultului, dar un diagnostic ct
mai precoce pentru o astfel de categorie de pacieni
i un tratament adecvat determin o mbuntire
mai rapid a simptomatologiei. Pe de alt parte, n
situaia n care debutul simptomatologiei este sub
vrsta de 13 ani, apar forme atipice i subclinice ale
tulburrii afective bipolare (8). n cazul prezenei
unei ciclri rapide, simptomatologia include epi-
soade mixte, evoluie cronic, labilitate emoional
i episoade maniacale sau depresive cu manifestri
discrete. Copiii pot prezenta manifestri explozive,
iar modicrile comportamentale sunt mai degrab
continue, dect episodice. n timpul unui episod
ma niacal, copiii manifest n general iritabilitate i
mai rar dispoziie euforic. Adolescenii diagnos-
ticai cu tulburare afectiv bipolar prezint o simp-
tomatologie similar cu cea a adulilor i episoade
afective distincte, cu un debut rapid al simpto ma-
tologiei. n cazul episoadelor afective, simptoma-
tologia este clasic i diagnosticul este mai uor de
identicat. Tabelul 1 prezint difereniat tulburarea
afectiv bipolar n funcie de vrst (dup Academy
of Child and Adolescent Psychiatry) (9).
Toate aceste simptome ale tulburrii afective bi-
polare pot inuenate de contextul cultural. Astfel,
un studiu efectuat pe pacienii din populaia Amish
a descoperit c tinerii pacieni diagnosticai cu un
episod maniacal prezint o serie de simptome, cum
ar ideaia de grandoare, reduse n intensitate, din
cauza limitelor de natur religioas. De ase menea,
studiile au artat faptul c acei copii pro venii din
minoritile etnice cu un nivel socio economic redus
au un risc mai mare de diagnosticare greit a unei
schizofrenii comparativ cu ali pa cieni cu tulburare
afectiv bipolar, deoarece epi soadele maniacale
prezint frecvent i simptome psihotice. n plus,
diferenele rasiale pot inuena i managementul
terapeutic (10). Un studiu asupra particularitilor
terapeutice a descoperit faptul c adolescenii
afroamericani cu tulburare afectiv bi polar primesc
de dou ori mai multe antipsihotice dect cei de
origine caucazian, din cauza interpre trii greite a
unor simptome. (11) Scopurile prin cipale ale mana-
gementului terapeutic din tulburarea afec tiv
bipolar sunt reprezentate de mbuntirea simp to-
matologiei i de prevenirea recderilor, avndu-se
n vedere reducerea morbiditii pe ter men lung i
asigurarea unei dezvoltri ct mai nor male a acestor
tineri. Trialurile clinice controlate, efectuate pe
tineri, sunt limitate, dar s-a constatat c cele mai
utilizate medicamente cu rol normo sta bilizator sunt
reprezentate de Litiu, Carbamazepin i Valproat.
De obicei, strategiile terapeutice n ca zul copiilor i
adolescenilor sunt bazate pe expe riena clinic cu
pacienii aduli. Dar, simpto ma tologia afectiv
prezent la tineri nu se suprapune ntotdeauna cu
cea a adulilor i ar necesare trialuri clinice
specice ecrei vrste pentru a putea identica un
tratament adecvat. naintea ini ierii oricrei terapii
psihofarmacologice este ne cesar s se obin un
consimmnt informat adec vat, s se evalueze
corect faza de evoluie a tulburrii afective i s se
estimeze, pe ct po sibil, durata tratamentului. Ale-
gerea terapiei adec vate se bazeaz pe urmtoarele
principii: (12)
evidenierea ecacitii medicaiei alese;
faza de evoluie a tulburrii psihice;
TABELUL 1. Evoluia clinic a tulburrii afective bipolare
n funcie de vrst
Perioada
prepubertal i
adolescena precoce
Perioada de
adolescen tardiv
i adult
Episod iniial Depresiv Maniacal
Tipul
episoadelor
Ciclare rapid,
episod mixt
Discret cu debut
brusc i sfrit distnct
Durata Cronic, ciclare
contnu
Sptmni
Funcionalitate
episodic
Fr episoade Funcionalitate bun
REVISTA ROMN DE PEDIATRIE VOLUMUL LXI, NR. 2, AN 2012 132
prezena altor tipuri de simptome cum ar
ciclarea rapid, simptomele psihotice sau
mo dicrile dispoziionale;
efectele adverse ale medicaiei;
istoricul pacientului legat de rspunsul la
medicaia anterioar;
preferinele pacientului i ale familiei.
Psihoterapia reprezint un alt element important,
parte integrant a managementului terapeutic. Se pot
dezvolta msuri educaionale adecvate n urma con-
sultrii familiei i a educatorilor i astfel pa cientul i
rudele sale vor nva s managerizeze aceast tul-
burare psihic. Msurile psihoterapeutice trebuie s
e adaptate la necesitile pacientului i implic mo-
daliti de nvare de ctre pacient a simptomelor
pro dromale ce vor prezice un viitor episod afectiv, ba-
zndu-se pe o serie de factori pre dictori, cum ar
de privarea de somn, modicrile situaionale, patternul
sezonier, abuzul de droguri sau noncompliana la tra-
tament (13). Psihiatrul trebuie s realizeze un plan
tera peutic folosind un algoritm asemntor celui din
gura urmtoare (14):
Litiu sau valproat (nu este rspuns)

Litiu+valproat (nu este rspuns)

Carbamazepin (nu este rspuns)

Carbamazepin + litiu (nu este rspuns)

Olanzapin sau risperidon (nu este rspuns)

Noile anticonvulsivante (nu este rspuns)

Terapia electroconvulsivant
Pentru psihiatri este foarte important s neleag
cnd s iniieze i cnd s discontinue terapia cu
normostabilizatori. Deoarece exist doar cteva
studii la copii i adolesceni cu tulburare afectiv
bipolar privind evoluia acesteia, experiena clinic
este cea care furnizeaz cele mai utile informaii
le gate de terapie. Astfel, experiena clinicienilor su-
gereaz faptul c nivelul terapeutic al timosta bili-
zatorilor trebuie meninut pentru minimum 2 ani,
dup ce s-a obinut remisia simptomatologiei.
Uneori, n cazul adolescenilor este necesar discon-
tinuarea trata mentului. Aceast discontinuitate tre-
buie efec tuat foarte lent, n timp, cu o reducere a
dozelor pe parcursul a minimum 6 luni. (15)
Diagnosticarea i tratarea tulburrilor afective
bipolare la copii i adolesceni rmne o problem
dicil avndu-se n vedere complexitatea feno-
meno logiei i evoluiei acestei tulburri. Terapia
farmacologic este necesar n scopul asigurrii
unei remisiuni adecvate, dar acest tip de pacieni
sunt frecvent subdiagnosticai i tratai necores-
punztor. Astfel, vor necesare i n continuare nu-
meroase cercetri pentru a evalua necesitatea mo-
noterapiei sau a combinaiilor terapeutice la tinerii
pacieni, deoarece este absolut necesar o intervenie
precoce i chiar agresiv n cazul acestora.
REVISTA ROMN DE PEDIATRIE VOLUMUL LXI, NR. 2, AN 2012 133
Clinical and therapeutical approaches of children and adolescent
bipolar disorders
Alexandra Bolos, Anamaria Burlea, Roxana Chirita
Universitatea de Medicin i Farmacie Gr. T. Popa, Iasi
ABSTRACT
Bipolar disorder remains a condition which it is underdiagnosed and misdiagnosed among children and
adolescents. The specic traits, like rapid cycling and mixed episodes often complicate the diagnosis. In
additional, overlapping and comorbid conditions may inuence the differential diagnosis. Thus, it is necessary
that age specic studies may produce diagnostic criteria specic for younger patients because an earlier and
accurate diagnosis will determine an adequate therapeutically management.
Key words: bipolar disorder, children, diagnosis, therapy
Child psychiatric disorders are more difcult to
characterize than those of adults. Although there
are important advances in diagnosis of psychiatric
disorder at children, many treatments are prescribed
for vaguely dened disorder like aggressiveness,
difcult behavior or depression. There are some
factors which contributed to this (1):
children have been neglected in psychiatric
services;
abnormality in children is inuenced by
maturation and development, that make more
difcult for doctors to interpret indicators of
brain dysfunction;
differential diagnosis is more difcult to
realize compared with adult caused to lack of
richness of behavioral expressions of psycho-
pathology at children;
children had a lot of difculties to describe
psychopathological symptoms.
Affective bipolar disorders had a variable age of
onset and it is especially diagnosed between ages
of 18 and 24, but 59% of adults experienced their
rst episode under the age of 18. The symptoms of
bipolar disorders are variable among children and
adolescence and they had a lot of overlapping and
comorbid conditions like ADHD or substance
abuse. (2,3)
Thus, we want to point on fact that a good
number of children presented with bipolar disorder
are misdiagnosed and this review offers a little
solution to the problem of an early diagnosis, which
it is critical for a good efcacy of treatment. An
early diagnosis of bipolar disorder is a very
important clinical objective for psychiatrists for
some reasons (4):
This psychiatric disorder is a source of serious
psychosocial dysfunction for children and
adolescents with important consequences for
their lives;
There is evidence that a psychiatric syndrome
is longer it will become more refractory to
treatment.
There are three main diagnostic issues which are
very important to facilitate an early diagnostic of
bipolar disorder in children and adolescents (5):
to identify symptoms suggestive for mania;
to differentiate between mania and ADHD,
when there are not psychotic symptoms;
to discriminate between mania and schi-
zophrenia, when there are psychotic sym-
ptoms.
To estimate the prevalence of bipolar disorder
among children and adolescent is very difcult
because there are only a few studies on this type of
population. Even, in the past, it is believed that
bipolar disorder occurred rarely among children
and adolescent, nowadays it is recognized that this
disorder is frequently, but prevalence is still
unknown. The prevalence rates depend on diagnostic
criteria used. (6) The DSM IV presents the same
criteria of diagnosis for all types of patients with
bipolar disorders regardless of age. However, the
clinicians should consider developmental issues
when it is necessary to evaluate children or adoles-
cents. (7) Thus, it is important for all of us to
understand this disorder from a developmental
perspective. For example, some young persons who
express rapid cycle episodes and hypomania may
do not have criteria for an adult bipolar disorder,
but an early diagnosis and treatment for such
REVISTA ROMN DE PEDIATRIE VOLUMUL LXI, NR. 2, AN 2012 134
patients it is important because early intervention
means an improved outcome. On the other hand,
often, patients with onset of the disorder younger
than 13 years old had atypical and subthreshold
forms of bipolar disorder. (8) For those with rapid
cycling form, symptoms include mixte state,
chronic evolution, emotionally labile behavior and
less discrete episode of mania or depression.
Children can experience explosive outbursts and
changes in mood are continuous in course, rather
than episodic. During a manic episode, children
manifest irritability more than euphoric mood.
Adolescent patients with bipolar disorder had
symptoms like adult patients and experience distinct
episode, unlike children with rapid onset of the
symptoms. Also, they present classical symptoms
of mania and can be easily diagnosed with bipolar
disorder. Table 1 summarizes differences in bipolar
disorder based on age of onset (from American
Academy of Child and Adolescent Psychiatry).(9)
TABLE 1. Clinical course of bipolar disorder by age of
onset
Prepubertal and
young adolescent
Older adolescent and
adult
Inital episode Depressive Manic
Type of
episodes
Rapid-cycling,
mixed
Discrete with sudden
onsets and clear osets
Duraton Chronic,
contnuous cycling
Weeks
Interepisodic
functoning
Nonepisodic Improved functoning

All these expression of bipolar symptoms and
behavior may be inuenced by cultural context.
Thus, a study on old order Amish patients found
that among Amish youths manic symptoms, like
grandiosity were diminished by religious ties. Also,
studies had shown that children from ethnic mi-
norities with lower socioeconomic backgrounds
had a greater risk of misdiagnosis of schizophrenia
than other patients with bipolar disorder because
manic episodes include frequently psychotic fea-
tures. In addition, racial differences can inuence
treatment patterns. (10) A study on treatment pat-
terns found that African American adolescents with
bipolar disorder were twice as likely as Caucasians
ones to receive treatment with antipsychotic cause
to misinterpretation of the symptoms. (11)
Therapeutic management of bipolar disorder
had two principals goals: to improve patient
symptoms and to prevent relapses in order to reduce
long term morbidity and to have a normal growth
for these children. Controlled medication trials in
younger patients are limited, but the most common
drugs used are Lithium, Valproat, Carbamazepine.
Therapeutically strategies for children and adoles-
cents with bipolar disorder are based mostly on
clinical experience with adult patients. But, mani-
festation of bipolar disorder in youths doesnt mime
adult type of bipolar disorder and it is necessary
more controlled trial age specic to determine
which therapy is most useful for youths. Before
initiating psychopharmacological treatment it is
recommended to obtain an appropriate informed
consent, to evaluate the phase of disorder and to
estimate the length of treatment. The choice of me-
dication is based on the following guidelines (12):
evidence of efcacy of the drug;
phase of the disorder;
the presence of other symptoms like rapid
cycling, mood changes or psychotic features;
side effects of the drug;
the history of the patient regarding the
response to drug;
preferences of patient and family.
Psychosocial treatment represents also a part of
an integrated approach of the therapeutically ma-
nagement. It can be develop an appropriate learning
environment by consultation with families and
educators, thus patients and family are taught to
cope with this disorder. Psychotherapy should be
exible on the necessities of the patient and it involves
teaching the patient to predict future epi sode relapses
based on some factors like sleep de privation, situational
changes, seasonal patterns, sub stance abuse and non-
compliance to treatment. (13)
Psychiatrists should realize a plan of treatment
using an algorithm like in the next gure. (14)
Lithium or valproat (if no response)

Lithium+valproat (if no response)

Carbamazepine (if no response)

Carbamazepine+lithium (if no response)

Olanzapinum or Risperidonum (if no response)

Newer antiepileptic drugs (if no response)

Electroconvulsive therapy
For psychiatrists, it is also important to
understand when to initiate and when to discontinue
the therapy. Because there are only a few studies
performed in children and adolescents with bipolar
disorders regarding the course of the disorder,
clinical experience provide us a lot of information
useful for treatment. Thus, clinical experience
REVISTA ROMN DE PEDIATRIE VOLUMUL LXI, NR. 2, AN 2012 135
suggests that therapeutic levels of mood stabilizers
should be maintained for at least 2 years after the
resolution of the symptoms. Also, adolescent pa-
tients may request discontinuation of the treatment.
Discontinuation must occur very slowly and doses
should be tapering over 6 month period. (15)
Diagnosis of bipolar disorder in children and
adolescents is complicated by the complexity of the
phenomenology and course of the disorder. The
pharmacological treatment is necessary for a good
outcome, but often this kind of patients are mis-
diagnosed and undertreated. Thus, more research is
required to evaluate monotherapy or combination
of therapies at youths because it is important to
have an early and even aggressive intervention at
these patients.
Gagan Joshi, Carter Petty, Janet Wozniak, Stephen V. Faraone, et al. 1.
A prospective open-label trial of quetiapine monotherapy in preschool
and school age children with bipolar spectrum disorder Journal of
Affective Disorders. Oct 2011
O. Bonnot, L. Holzer 2. Utilisation des antipsychotiques chez lenfant et
ladolescent Neuropsychiatrie de lEnfance et de lAdolescence. Sep
2011
Howard Y. Liu, Mona P. Potter, K. Yvonne Woodworth, Dayna M. 3.
Yorks, Carter R. Petty, et al. Pharmacologic Treatments for Pediatric
Bipolar Disorder: A Review and Meta-Analysis Journal of the American
Academy of Child & Adolescent Psychiatry. Aug 2011, Vol. 50, No. 8:
749-762.
Jonathan C. Pfeifer, Robert A. Kowatch, Melissa P. DelBello 4.
Pharmacotherapy of Bipolar Disorder in Children and Adolescents CNS
Drugs. Jul 2010, Vol. 24, No. 7: 575-593
Eric Taylor 5. Managing bipolar disorders in children and adolescents
Nature Reviews Neurology. Sep 2009, Vol. 5, No. 9: 484-491
N.C. Patel, D.M. Patrick, E.A. Youngstrom, S.M. Strakowski, M.P. 6.
Delbello Response and Remission in Adolescent Mania Journal of the
American Academy of Child & Adolescent Psychiatry. May 2007, Vol. 46,
No. 5: 628-635
Diagnostic and Statistical Manual of Mental Disorders, 7. 4th Edition
(1994) American Psychiatric Association, Washington DC.
Edith M. Jolin, Elizabeth B. Weller, Ronald A. Weller 8. The public
health aspects of bipolar disorder in children and adolescents Current
Psychiatry Reports. Apr 2007, Vol. 9, No. 2: 106-113
Michael Strober, Boris Birmaher, Neal Ryan, David Axelson, Sylvia 9.
Valeri, Henrietta Leonard, et al. Pediatric bipolar disease: current and
future perspectives for study of its long-term course and treatment
Bipolar Disorders. Aug 2006, Vol. 8, No. 4: 311-321
Nick C. Patel, Melissa P. DelBello, Robert A. Kowatch, Stephen M. 10.
Strakowski Preliminary Study of Relationships Among Measures of
Depressive Symptoms in Adolescents with Bipolar Disorder Journal of
Child and Adolescent Psychopharmacology. Jun 2006, Vol. 16, No. 3:
327-335
Cassano G.B., McElroy S.L., Brady K., Nolen W.A., Placidi G.F. 11.
Current issues in the identication and management of bipolar spectrum
disorders in special populations. J Affect Disord. 2000; 59 (suppl 1):
S69-79
Saunders and Goodwin 12. The course of bipolar disorder Adv. Psychiatr.
Treat. 2010; 16:318-328.
Geller et al. 13. Child Bipolar I Disorder: Prospective Continuity With Adult
Bipolar I Disorder; Characteristics of Second and Third Episodes;
Predictors of 8-Year Outcome Arch Gen Psychiatry 2008; 65:1125-1133
Goldstein 14. Recent Progress in Understanding Pediatric Bipolar
Disorder Arch Pediatr Adolesc Med 2012; 166:362-371.
Rick T. Bowers, Christina G. Weston, Julia Jackson 15. Child and
Adolescent Affective Disorders and their Treatment Journal of Affective
Disorders. Mar 2012: 189-214
REFERENCES