Psychopharmacology Nuts and Bolts

Medications and Things to Know:

- Always think DRUGS in ANY DDx, could it be an adverse effect, side effect, drug-drug
interaction, overdose or noncompliance
- Pregnancy - there are basically no psychotropic drugs that are rated better than Class C
- Off label use of medications is very common in psychiatry

ANTIDEPRESSANTS
-

Overall, most of these medications have the same efficacy for treating depression, the
main difference is side effects
Most antidepressants take a minimum of 2-4 wks to have initial efficacy; a trial of 6-8 wks
at a therapeutic dose would be considered an adequate trial for most
Any Antidepressant may induce a manic state in pts with a predisposition (they would not
require a prior diagnosis of Bipolar disorder as this may be the sentinel event)

- There may be an inc risk for suicidal ideation in any pts taking an antidepressant
Tricyclics
Imipramine (used to treat enuresis)
Amitriptyline
Doxepin
Nortriptyline
Clomipramine
Desipramine
MoA - inhibition of serotonin and NE uptake
Indications Depression, dysthymia, OCD, panic d/o, PTSD, chronic pain (TCA>> SSRI)
Side Effects
- Anticholinergic (dry eye, mouth, constip, urinary retention, blurred vision, AMS (inc risk in
elderly 2/2 muscarinic blockade)
- Histaminic sedation, wt gain
- Alpha -1 adernergic blockade - orthostatic hypotension, falls
- Possilbe EKG changes, arrhythmias (prolonged QY and PR, AV block) * In
OVERDOSE=widened QRS
Pearls
- Cheap but dirty
- Require diet modification to avoid HTN crisis (avoid tyramine containing foods)
- Cannot be combined with other antidepressants (risk of serotonin syndrome) or
sympathomimetic drugs; avoid with cough syrup or Demerol
- SERIOUS RISK IN OD
SSRIs
Flouxetine (Prozac)
20-80mg daily dosing range
Sertraline (Zoloft)
50-200mg/day
Paroxetine (Paxil)
20-80mg/day
Citalopram (Celexa)
20-60mg/day
Fluvoxamine (Luvox)
50-300mg/day
Escitalopram (Lexapro)
10-30mg/day
MoA blocks reuptake of serotonin at the presynaptic nerve terminals
Indications depression, panic d/o, OCD (typically dose upper limits), bulimia, pain d/o, GAD,
social phobia, PTSD,
PMDD ; in elderely, pts with panic d/o and in children start at doses the nl starting dose or
less

Side Effects (SSRIs)

- GI upset, HA, insomnia, sexual dysfcn
- Hypernatremia in the elderly
- Prozac/Zoloft tend to be more activating
- Paxil tends to be more sedating
- Lovox tends to have more drug-drug interactions
Pearls
- Typically fewer side effects and very safe
- Risk of serotonin syndrome when used with other serotonin meds (SSRIS, TCAs, MAOS,
demerol, St. Johns Wart)
- Serotonin Syndrome may present as a delirium (AMS, restless, shivering, VS abnl 2/2
autonomic instability (inc HR,BP,temp), hyperreflexia may lead to shock, coma, death A
MEDICAL EMERGENCY
-

Discontinuation syndrome common, particularly if taper too quickly, esp with shorter
acting agents (does not happen with Prozac 2/2 long life) presents as flu-like
symptoms (GI upset, sleep disturbance, mood chngs, dizziness, lethargy resolve when
restart med

Other Antidepressants
Venlafaxine (Effexor)
dosing range 75-375mg/day
- Blocks reuptake of Serotonin and Norepinephrine
- May elevate BP
Duloxetine (Cymbalta)
dosing range 60-120mg/day
- Blocks serotonin and NE transporters; metabolized through CYP2D6 pathway sig drug
interactions
- Indications include depression and chronic pain d/o (fibromyalgia as well)
- Newer and very expensive
Buproprion (Wellbutrin, Zyban)
dosing range 75-400mg/day
- Increased dopamine activity
- Indications include MDD, dysthymia, Bipolar depression, ADHD (at low doses), used for
smoking cessation
- Contraindications for use include h/o sz d/o, head trauma or anorexia/bulimia
- No sig sexual side effects
- NOT effective for anxiety; can actually worsen anxiety/agitation
Mirtazipine (Remeron)
dosing range 7.5-45mg/day
- Alpha 2 adernergic antagonist, enhances noradnergic and serotenergic
- Sedation and wt gain are sig side effects; often used in depression for those with insomnia
and poor appetite; no sig sexual side effects
- Effective in combo with SSRI for augmenting treatment of depression
Desyrel (Trazodone)
dosing range 25-600mg
- MoA includes primary inhibition of presynaptic serotonin reuptake with possible mild
postsynaptic sertonertic antagonism. Does of AEs 2/2 to histaminic, anticholinergic and
alpha-1 blockades
- Used most commonly as a sleep aid rather than as antidepressant
- Effective at low doses (25mg 200mg) for sleep, requires higher dosing for antidepressant
properties (200-600mg)
- PRIAPRISM in 1/6000 pts
Nefazodone (Serzone)
- Is an analog of Trazodone

Sedating, less sexual side effects

Many drug-drug interactions 2/2 p450 inhibition by a metabolite
Inc risk of hepatic failure

MOOD STABILIZERS
Lithium
MoA unclear; second messenger system effect effect on circadian rhythms and augments
serotonin fnc. Renally cleared and can cause sig renal impairment (esp if dehydration, use of
NSAIDS, thiazide diuretics and in elderly
Indications BPAD, Schizoaffective d/o, augmentation for depression, mood lability
Side effects
- GI upset, fatigue, fine tremor, confusion
- Toxicity AMS, N/V, slurred speech, course tremor, ataxia
- Cardiac conduction problems 1st degree block, slowed sinus node, PVCs
- Renal impairment (DI, rare nephritic syndrome)
- Hypothyroidism in 5%
Pearls
- Pregnancy Class D EBSTEINs Anomely ht defect at tricuspid valve; avoid in 1 st
Trimester
- Requires blood level monitoring, has narrow therapeutic window (0.8-1.2); dialysis rec for
levels greater than 4.0
- Steady state takes 5 days
- LETHAL in OD
Valproic Acid (Depakote)
MoA unknown; ? if changes metabolism of GABA
Indications BPAD (esp for rapid cycling mania), Schizoaffective d/o, aggression, impulse control
probs
Side effects
- N/V; sedation, tremor, wt gain
- Blood abnormalities (thrombocytopenia)
- Liver dysfcn (rare hepatotoxicity) and very rare Hemorrhagic pancreatitis
Pearls
- Metabolized by liver, via P450 pathway multitude of drug-drug interactions
- PREGNANCY CLASS D 2/2 neural tube defects
- Requires blood level monitoring, but wide therapeutic window
- Steady state reached in 3 days
Carbamazapine (Tegretol)
- Less effective, not as widely used
- Serious side effects include blook abnl (aplastic anemia, agranulocytosis); severe rash
- Preg Class D
- Can be risky in OD, particularly 2/2 other drug-drug interactions
Lamotrigine (Lamictal)
- Used for Bipolar depression, not for manic state; commonly used for augmentation of
antidepressant medications
- 10% incidence of rash, cases of Stevens-Johnson have occurred, particularly when dosed
to high too fast
- Requires slow titration to get to effective dosing (start at 25mg and inc by 25mg every 2
wks; target range is ~200mg)
Other Mood Stabilizers include other anticonvulsants (Gabapentin, Topiramate) but overall
less effective and poor outcome data

ANTI-PSYCHOTICS
-

Typical and Atypicals are equally effective (CATIE trial) for treatment of symptoms.
Primary difference is side effect profiles and new agents tend to be better tolerated
- Although some effect may seen within hours of dosing, real antipsychotic effects can take
3-6 wks to materialize as meds reach a steady state
- Extrapyramidal Side Effects (EPS)
o Parkinsonism shuffled gait, rigidity, masked facies, drooling, tremor
o Acute Dystonia slow/sustained muscle contractions (neck, lock jaw, eyes); Rx with
Cogentin or Benadryl IM scary but reversible
o Akathesia inner restlessness, need to pace/rock; Rx with Inderal or BZDs
o Tardive Dyskinesia often longterm, may be irreversible abnl, invol mvmt of face,
limbs, trunk. Rx but stopping agent and changing to new antipsychotic med
- Neuroleptic Malignant Syndrome (NMS) potentially lethal reaction to antipsychotic meds,
rapid onset. Presentation may consist of elevated temp, muscle rigidity, VS instability,
AMS. Medical emergency requires urgent intervention and possible ICU admission, Rx w/
d/c of antipsychotic, IVF, and possibly bromocriptine/dantrolene
Traditional Neuroleptics (Typicals, 1st Generation)
Haloperidol (Haldol)
5-20mg/day dosing range High Potency
Trifluoperazine (Stelazine)
5-20mg/day
High Potency
Fluphenazine (Prolixin)
10-20mg/day
High
Potency
Thiothixene (Navane)
5-20mg/day
High Potency
Pimozide (Orap)
1-10mg/day
High Potency
Molindone (Moban)
Loxapine (Loxitane)
Perphenizine (Trilafon)

50-100mg/day
50-100mg/day
4-40mg/day

Mesoridazine (Serentil)
Chlopromazine (Thorazine)
Thioridizine (Mellaril)

50-400mg/day
200-800mg/day
200-800mg/day

Mid Potency
Mid Potency
Mid Potency
Low Potency
Low Potency
Low Potency

MoA Dopamine D2 receptor Antagonism (High, Mid, Low potencies depend on binding affinity)
Lower potency typically require higher dosing to elicit antipsychotic effect
Indications Schizophrenia, psychosis 2/2 primary mood d/o/dementia/delirium, schizoaffective
d/o, severe agitation, tics
Side Effects
- Lower potency agents have more troublesome side effects 2/2 greater antagonism of
cholinergic, adrenergic and histaminergic receptors
- High potency agents have more frequent EPS effects 2/2 potent antagonism of dopa
receptors
- Wt gain, sexual dysfcn, orthostatic hypotension, decreased sz threshold
- Prolonged QTc risk of Torsades
Pearls

Compliance is a HUGE issue and can be rare at times. Haldol and Prolixin come in
injectable depot forms (req q monthly dosing once at steady state)

Atypical Antipsychotics (new generation)

Clozapine (Clozaril)
400-600mg/day
Olanzapine (Zyprexa)
5-20mg/day
Risperidone (Risperdal)
1-6mg/day
Aripiprazole (Abilify)
10-30mg/day
Quetiapine (Seroquel)
200-800mg/day
Ziprasidone (Geodone)
80-160mg/day

Check blood levels

MoA Prominent antagonism at Serotonin 2A receptor as well as Dopamine D2 blockade; less

action on nigrostriatal pathway (where EPS Symptoms are thought to originate)
Indications same as above
Side Effects
- Clozapine Agranulocytosis in 1-2%, requires CBCs weekly while starting, monthly
forever; lowers sz threshold. Myocarditis. Commonly causes tachycardia, hypotension,
drooling
- Common SEs for all include metabolic syndrome (wt gain, hypercholesterol, DM); sedation,
orthostatic hypotension
- EPS lower frequency; inc frequency in pts who are neuroleptic niave
- TD much less incidence, but may still occur
- Cardiac side effects, QTc prolongation; independent cardiovasc risk for all taking atyipcals
(inc risk of ischemic stroke) despite length of time taking
- Risperdal has risk of elevated prolactin (amenorrhea, gynecomastia, galactorrhea and
impotence)
Pearls
- Risperdal comes in long acting injectable
- Abilify, Geodone, Zyprexa come in short acting injectable (often used in acute settings)
- Abilify, Risperdal, Zyprexa all come in dissolvable tablet formulation (helpful for
noncompliance)
- Have benefit in treating particularly negative symptoms and most have mood stabilization
properities (Seroquel, Abilify and Geodone have FDA approval as primary agents for
BPAD manic/mixed state)
- Clozaril is the go to agent for treatment refractory schizophrenia

ANTIPARKINSONIAN DRUGS
Benztropine (Cogentin)
Trihexyphenidyl (Artane)
Biperiden (Akineton)
MoA Anticholinergic effect, restores ACh/Dopa balance
Indications treatment of EPS side effects assoc w/ antipsychotic drugs
Side Effects
- Dry mouth, blurred vision, constipation, confusion/AMS, delirium
Pearls
- Artane has euphorigenic properties and is at risk of being abused
- Amantadine is an alternative treatment (mech is a dopa agonist)

ANTI-ANXIETY MEDICATIONS

SSRIs see above

Benzodiazepines *these are controlled substances
Clonazepam (Klonopin)
18-50hr life
Alprazolam (Xanax)
6-12hr life
Lorazepam (Ativan)
10-20hr life
Diazepam (Valium)
20-100hr life
Chlordiazepoxide (Librium)
5/30hr life
Clorazepate (Tranxene)
36-200hr life
MoA (BZDS) work at GABA receptor (like EtOH) to cause CNS depression
Indications panic d/o, severe anxiety, agitation, agitated depression, social phobia, akathesia,
insomnia, acute EtOH withdrawal. Often used for initial treatment of anxiety until SSRI
therapeutic
Side Effects
- Sedation, drowsiness, dizziness (Feelings of being intoxicated)
- Delirium, Respiratory suppression
- Dependence formation (physiological as well as psychological); AKA can develop tolerance
Pearls
- Just as EtOH, physical dependence can lead to withdrawal syndrome upon abrupt
cessation as well as risk of seizure, coma and death
- Caution in gero population, metabolites can often build up excessively with significantly
prolonged lives and dangerous blood levels recommend minimal use to avoidance
- Can be lethal in OD
Buspirone (BuSpar) not a controlled substance
- Mild effect for GAD; may be used for augmentation of antidepressant treatment
- Common SEs HA, N/V, dizziness
- No risk of dependence or developing tolerance
- Safe in OD
Hydroxyzine (Vistaril, Atarax) not a controlled substance
- MoA antihistaminic (used for treatment of anxiety as well as purities)
- Likely deliriogenic in elderly 2/2 anticholinergic properties

SUBSTANCE ABUSE
Disulfuram (Antabuse)
- Req pt to be strongly motivated, only by taking than causes severe rxn if EtOH ingested
(N/V)
- Contraindicated if pt with liver dis
Naltrexone (Revia)
- Dec craving by targeting pleasure pathway in brain
- Often pts will dec but not completely abstain from use
Methadone controlled substance
- Rx of heroin dependence
Buprenorphine (Suboxone) controlled substance
- Tx opioid dependence

DEMENTIA
Acetylcholinesterase Inhibitors (used to treat mild-moderate dementia of Alzheimers type)
Donepezil (Aricept) reversible, selective inhib
o Decreases breakdown of Acetylcholine in brain ( inhibits acetylcholinesterase)
o More specific and less GI side effects
Rivastigmine (Exelon) reversible, selective inhib

o also available as a patch

Galantamine (Reminyl) reversible, competitive inhib
NMDA Antagonist (used to treat moderate to severe dementia of Alzheimers type)
Memantine (Namenda)- noncompetitive NMDA antagonist, reduces glutamate
mediated excitotoxicity
Vitamin E antioxidant, thought to prevent cell death

HYPNOTICS
Benzodiazepines
Zolpidem (Ambien)
Zaleplon (Sonata)
Eszopiclone (Lunseta)
Desyrel (Trazodone)

ADHD MEDICATIONS
Stimulants
- All work equally well, but individuals may differ in response
- Quick onset of action and effect (same day is possible)
- May require multiple daily doses
- All stimulants are controlled substances
- FDA Approval Adderall and Dexedrine for age 3 and up; all other stimulants for age 6 and
up
Methylphenidate
o Short Acting forms (Ritalin, Methylin, Focalin)
o Long-Acting forms (Ritalin LA and SR, Metadate ER and CD, Methylin ER, Focalin XR,
Concerta, Daytrana Patch)
Amphetamines
o Short-Acting forms (Adderall, Dexedrine, Dextrostat, Desoxyn)
o Long-Acting forms (Adderall XR, Dexedrine Spansule, Vyvanse)
Atomoxetine (Strattera)
- MoA more like antidepressant than stimulant
- Gen considered 2nd line; recommendation would be to try 3 separate stimulant trials prior
to starting
- Consider 1st line when h/o substance abuse, h/o anxiety or parents requesting noncontrolled substance
- FDA approved from age 6 and above
- May take weeks to be effective, requires daily use and strict compliance
- Same black box warnings as antidepressants
Non-FDA Approved 2nd to 3rd line agents
Buproprion
Modafanil (used for treatment of narcolepsy)
Clonidine (antihypertensive; also used in children for treatment of aggression/agitation)
Amantadine (treatment for influenza, MoA dopamine agonist)