PSYCHOPHARMACOLOGY: AN INTRODUCTION

OVERVIEW:
Medications for the treatment of anxiety disorders, insomnia, schizophrenia, bipolar disorder, and depression will be reviewed including:
- Sedatives, Anxiolytics, and Hypnotics
- Neuroleptics/Antipsychotics
- Antidepressants
- Mood Stabilizers

In psychiatry:
- Health care providers need to MONITOR efficacy and toxicity
- Polypharmacy is common
- Minimum and maximum doses are only guidelines & available studies are less than ideal
- Treatment is often practitioner-specific/empiric
SEDATIVES, ANXIOLYTICS, AND HYPNOTICS
PEAK IN ADVERSE
DAILY
GENERIC NAME BRAND NAME INDICATIONS PLASMA HALF-LIFE EFFECTS
DOSE (MG)
(PO)
BENZODIAZEPINES
Withdrawal Symptoms: sweating, tremor, nausea, vomiting, rebound anxiety, increased heart rate, insomnia, twitching,
visual/tactile hallucinations, SEIZURES (onset within 1-2 days, avoid by tapering benzos after long-term use)
Clonazepam Rivotril® 0.5 – 2 Insomnia, 1-2h 20-50h Sedation, dizzy,
Diazepam Valium® 5 – 60 panic attacks, 1-2h 30-200h “hangover”,
Lorazepam Ativan® 1–6 anxiety, 1-6h 10-25h amnesia, increased
®
Oxazepam Serax 15-30 alcohol 2-3h 5-20h falls/fractures,
Temazepam Restoril® 0.25 – 0.5 withdrawal, 1-2h 3 -25h dependence, 
acute mania, cognition,
akathisia delirium,
psychomotor
impairment
MISCELLANEOUS
Zopiclone Imovane® 7.5 - 15 Insomnia 1.5h 4-7h Bitter metallic
(benzodiazepine taste, “hangover”,
like mechanism) dry mouth
®
qMethotrimeprazine Nozinan Severe Weight gain, EPS,
(antipsychotic) insomnia anticholinergic
Quetiapine Seroquel® 12.5- 100 (need ADEs, tardive
(antipsychotic) antipsychotic dyskinesia
ANTIDEPRESSANTS
Trazodone Desyrel® 25 - 100 Insomnia 0.5-1.5h 7-10h Orthostatic
Depression hypotension
Mirtazapine Remeron® 5 - 25 1-3h 15-30h Hypotension, EPS,
anticholinergic
®
Amitriptyline Elavil 10 -50 <4h 15h Hypotension,
anticholinergic,
fatal in overdose
Additional benzodiazepine information:
Long Acting= good choice for tapering (ie. dizaepam, clonazepam)
Short Acting= better hypnotic and sedative properties but more rebound anxiety (ie. lorazepam)
LOT drugs (lorazepam, oxazepam, temazepam) preferred in elderly and liver dysfunction due to no active metabolites
Precautions: substance abuse history, sleep apnea, COPD, elderly, CNS depression, pregnancy (floppy infant syndrome;
possible teratogen & can precipitate withdrawal in newborns if used in 3rd trimester), clozapine-use (may lead to
significant sedation, excessive salivation, and rare respiratory arrest)
Length of therapy:
 Anxiety- use as an adjunct to antidepressants & re-evaluate < q4-6 weeks
 Sleep aid (hypnotic)- not to exceed 4 weeks

Prepared by Tasha Ramsey B.ScPhm, ACPR, PharmD student 2012 and Katelyn Halpape BSP, ACPR, PharmD student 2015
Adapted with permission from Gillian Lagnado B Sc Phm (Hons) PharmD BCPP. St Paul’s Hospital, Vancouver BC Canada
 NEUROLEPTICS/ANTIPSYCHOTICS
“Typical” Agents (similar molecular structures)/ First generation/ Conventional antipsychotics
- Block dopamine receptors in the limbic system of the brain (emotion, behaviour, long-term memory
- Effective against positive symptoms (hallucinations, delusions) of psychosis & useful for acutely agitated pts
-Adverse effect profile includes include extrapyramidal effects [Extrapyramidal system: neural network that is part of the motor system
that causes involuntary reflexes and movement and modulation of movement (ie. coordination)]
GENERIC ANTI-
DAILY DOSE
NAME/BRAND HYPOTENSION EPS SEDATION CHOLINERGIC ADVERSE EFFECTS
(MG)
NAME EFFECTS
Weight gain 2.1kg at 10
Chlorpromazine/ Low to
25 - 1200 High High Moderate weeks, jaundice,
Largactil® Moderate
seizures
Loxapine/
10 - 50 Low to moderate Moderate Low Low Minimal wt gain
Loxapac®
Haloperidol/
2 - 10 Low Very high High Moderate Wt gain ~ 0.5kg at 10 wks
Haldol®
“Atypical” agents (dissimilar molecular structures)/ Second generation
- Block dopamine and serotonin receptors within the limbic, cortex and niagra striatal pathways of the brain
- Effective against both positive and negative symptoms & for acutely agitated and psychotic patients
- Emerging adverse effect profile (lipids, glucose); most cause: wt gain, elevated glucose, elevated lipids
Agranulocytosis,
Clozapine/
® Very low seizures, sialorrhea,
Clozaril 200-500 High High High
(lowest) tachycardia, constipation, ↑
wt 3.9kg at 10 wks
Risperidone/ 2-5 mg oral or - Sedation, ↑ prolactin,
Low to
Risperidal® IM: 25-50 every 2 Moderate to high Low Very low ? ↑ stroke risk in elderly
moderate
wks ↑ wt 2kg at 10 wks
Olanzapine/ Transient increase in liver
Zyprexa® 5-30 Low Very low High Low function tests, ↑ wt 3.5kg
at 10 wks, 5.4kg @ 6 mos
Cataracts (in dogs),
Quetiapine/ Moderate to
100- 800 Low to moderate Very low Low hypothyroidism, ↑ wt
Seroquel® high
2.5kg/10 wks, 5.6kg/1yr
Akathesia, headache,
Aripiprazole/ anxiety, insomnia,
10 -30 Low Low Low Low
Abilify® dizziness, tremor, ↑ wt in
pts with BMI<23
↑ QTc, akathisia,
Ziprasidone/ 20 BID – 80 BID Low to dysmenorrhea, ↑ wt,
Low Moderate Low
Zeldox® Take with food moderate sialorrhea, priapism,
visual disturbances
Absorption ↑ 50% with
Paliperidone/ Low to high fat meal, ↑ QTc, Wt
3-9 Low Low Low
Invega® moderate ↑ 2kg/6mos, ↑ prolactin,
EPS
Akathisia, nausea, EPS,
Lurasidone/ 20-120 Low to agitation, drowsy, tremor,
Low Moderate Low
Latuda ® Take with food moderate minimal wt increase, less
↑ QTc & sexual AEs
5 BID- 10 BID May ↑ QT, EPS,
Asenapine/ Sublingual (wait Low to Low to akathisia, minimal ↑ wt,
Low Low
Saphris® 10 min after to moderate moderate mouth numbness, poor
eat/drink) taste
Illoperidone/
↑ QTc, EPS, BP,
Fanapt® (only 6-12 BID High Mod Low Low
fatigue
available in USA)
Prepared by Tasha Ramsey B.ScPhm, ACPR, PharmD student 2012 and Katelyn Halpape BSP, ACPR, PharmD student 2015
Adapted with permission from Gillian Lagnado B Sc Phm (Hons) PharmD BCPP. St Paul’s Hospital, Vancouver BC Canada
Drug Maintenance Dose Pharmacologic Depot Solution Comments
class
Typical Antipsychotic
Flupenthixol 20-40mg/d q2-4 Typical Sesame oil Peaks 4-7 days
decanoate/ weeks antipsychotic
Fluanxol®
Fluphenazine 25mg q2-4 weeks Typical Sesame oil Peaks 2-5 days
decanoate/ antipsychotic
Modecate®
Zuclopenthixol 150-300mg q2 Typical Coconut oil Peaks 3-7 days
decanoate weeks antipsychotic
/Clopixol®
Zuclopenthixol 25-50mg q3 days Typical Coconut oil Onset 2-4 hours,
acetate/ Accuphase® antipsychotic duration 2-3 days,
sedation @ 8 hours
Haloperidol 50-300mg q4 weeks Typical Sesame oil Peaks 3-9 days
decanoate/ antipsychotic
Haldol®
Atypical Antipsychotic
Risperidone long- 25-50mg q2 weeks Atypical Microspheres in Onset ~ 3 weeks and
acting/ antipsychotic diluent peak 4-6 weeks
Risperdal Consta® (bridge with oral
risperidone x 3
weeks)
Paliperidone/ Invega 25-150 mg q4 weeks Atypical PEG 4000, water After initial loading
Sustenna® antipsychotic for injection doses of 150 mg on
Day 1 and 100 mg on
Day 8 NO need for
overlap with oral
agents

Aripiprazole/ Abilify 400 mg q4 weeks Atypical Water for Continue oral

Maintena® antipsychotic injection aripiprazole for 14
days during initiation

General Monitoring Guidelines for Antipsychotics

- Vitals (including postural blood pressure and heart rate)
- Behaviours (improved psychosis & observe for signs of toxicity: akathisia, sedation and delirium)
- Weight
- Glucose, cholesterol
- EKG
- CBC (WBC, neutrophils)
- Signs of muscle rigidity/parkinsonism
- Signs of anti-cholinergic adverse effects (dry mouth, urinary retention, constipation, delirium)

Antipsychotic Indications
 Bipolar disorder, autistic disorder, major depressive disorder, schizophrenia, Tourette syndrome, PTSD,
delirium in critically ill patients, delusional parasitosis, psychoisis/agitation related to Alzheimer’s
dementia, MDD with psychotic features
Prepared by Tasha Ramsey B.ScPhm, ACPR, PharmD student 2012 and Katelyn Halpape BSP, ACPR, PharmD student 2015
Adapted with permission from Gillian Lagnado B Sc Phm (Hons) PharmD BCPP. St Paul’s Hospital, Vancouver BC Canada
Antipsychotic Specific Serious ADRs
Reaction Signs and Symptoms Treatment Most likely caused by
Acute dystonia Severe muscle spasm – may Benzotropine Typical antipsychotics
involve tongue, eyes, neck, torso, Diphenhydramine
legs and cause impaired breathing Lorazepam
Akathisia Inner restlessness, cannot sit still Propranolol Typical antipsychotics
Lorazepam
Anticholinergic toxicity Delirium, urinary retention, dry Stop drug if severe Typical antipsychotics,
mouth, blurred vision, tachycardia, clozapine
no sweating, constipation
Parkinsonism (EPS) Cogwheel rigidity, “mask-like” Benztropine Typical antipsychotics,
face, rigidity, shuffling gait, tremor, Diphenhydramine risperidone
motor slowing, drooling
Neuroleptic malignant Muscle rigidity, delirium, Stop offending Typical antipsychotics
syndrome diaphoresis/fever, increased CK, agents
autonomic instability Supportive care
Bromocriptine,
dantrolene,
lorazepam
QTc prolongation Arrhythmia, sudden death Stop offending Typical antipsychotics,
(QTc > 450ms) agents clozapine, ziprasidone,
others ex. TCAs
Tardive dyskinesia Involuntary movement of face, jaw, Stop offending Typical antipsychotics,
tongue, lips, eyes, limbs, trunk, agents (may not be risperidone
neck reversible)
Prolactin elevation Galactorrhea, menstrual Stop offending Typical antipsychotics,
disturbances, sexual dysfunction agents risperidone
Sexual dysfunction Stop offending Typical antipsychotics
agents

Prepared by Tasha Ramsey B.ScPhm, ACPR, PharmD student 2012 and Katelyn Halpape BSP, ACPR, PharmD student 2015
Adapted with permission from Gillian Lagnado B Sc Phm (Hons) PharmD BCPP. St Paul’s Hospital, Vancouver BC Canada
 ANTIDEPRESSANTS

SELECTIVE SEROTONIN RE-UPTAKE INHIBITORS (SSRIS): 5HT Selective

GENERIC NAME BRAND NAME DAILY DOSE (MG) ADVERSE EFFECTS & COMMENTS
Citalopram  10 – 40 - Headache, somnolence, nausea,
Celexa
Escitalopram Cipralex® 10 – 20 insomnia, sexual dysfunction, anxiety,
Fluoxetine  10 – 80 anorexia, tremor, diarrhea,
Prozac
constipation, SIADH
Paroxetine Paxil® 10 - 60
 - TAPER when discontinuing to avoid
Sertraline Zoloft 50 – 200
withdrawal syndrome

SSRI Withdrawal Syndrome:

F – flu-like symptoms
I – insomnia
N – nausea
I – imbalance (dizziness)
S – sensory disturbances (visual, paresthesias, electric shock-like sensations)
H – hyperarousal (agitation, restlessness)

Serotonin Syndrome:
 Concomitant use of multiple serotonergic agents
 Symptoms: delirium, agitation, fever, sweating, tremor, diarrhea,
uncoordinated, myoclonus (jerking contractions), hyperreflexia,
hypertension, tachycardia, death
 Treatment: supportive, discontinue serotonergic agents
 Serotonergic Agents:
o Antidepressants – MAOIs, TCAs, venlafaxine, St. John’s Wort
o Migraine medications – sumatriptan
o Other –linezolid, dextromethorphan, meperidine, tramadol,
ondansetron

Prepared by Tasha Ramsey B.ScPhm, ACPR, PharmD student 2012 and Katelyn Halpape BSP, ACPR, PharmD student 2015
Adapted with permission from Gillian Lagnado B Sc Phm (Hons) PharmD BCPP
St Paul’s Hospital, Vancouver BC Canada
 ANTIDEPRESSANTS CONTINUED

TRICYCLIC ANTIDEPRESSANTS (TCAS): 5HT & NE Effects

DAILY DOSE
GENERIC NAME BRAND NAME ADVERSE EFFECTS AND COMMENTS
(MG)
Amitriptyline Elavil® 50 – 200 - Anticholinergic (dry mouth, constipation blurred
Clomipramine Anafranil® 50 – 200 vision, urinary retention)
Imipramine Tofranil® 25 – 300 - Sexual dysfunction, rash, tremors
Desipramine Norpramin® 25 – 300 - ↑HR, ↓BP
Nortriptyline Aventyl® 10 – 150 -Fatal in overdose: due to cardiac & neuro-toxicity

MONOAMINE OXIDASE INHIBITORS (MAOIS): 5HT & NE Effects

GENERIC NAME BRAND NAME DAILY DOSE ADVERSE EFFECTS AND COMMENTS
(MG)
Phenelzine Nardil® 30-60 - Arrhythmias, headache, orthostatic hypotension
- Hypertensive crisis:
 Symptoms: headache, stiff neck, sweating,
nausea, vomiting
 AVOID tyramine containing foods (aged
cheeses, beer, processed meats, fava beans,
wine)
- WASHOUT period 2 wk

SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIS): 5HT & NE Effects

GENERIC NAME BRAND NAME DAILY DOSE ADVERSE EFFECTS AND COMMENTS
(MG)
Venlafaxine Effexor® 37.5 – 375 - Nausea, dry mouth, dizziness, constipation, sexual
dysfunction, mania, elevated BP/HR, tremor
Desvenlafaxine Pristiq® 50 – 100 - As for venlafaxine
- Active metabolite of venlafaxine
Duloxetine Cymbalta® 30 – 60 - As for venlafaxine

MISCELLANEOUS

GENERIC NAME GENERIC NAME GENERIC NAME GENERIC NAME

Trazodone Desyrel® 100 – 600 - Dizzy, headache, nausea, ↓BP
Mirtazapine Remeron® 15 – 45 - Somnolence, increased appetite, weight gain,
dizziness, dry mouth, constipation
Bupropion Wellbutrin® 100 – 450 - Agitation, insomnia, psychosis, weight loss,
Zyban® confusion, mania, SEIZURES
Prepared by Tasha Ramsey B.ScPhm, ACPR, PharmD student 2012 and Katelyn Halpape BSP, ACPR, PharmD student 2015
Adapted with permission from Gillian Lagnado B Sc Phm (Hons) PharmD BCPP
St Paul’s Hospital, Vancouver BC Canada
Bipolar Disorder
 There are two types of Bipolar Disorder:
o Bipolar Type I: Manic episodes + depressive episodes
o Bipolar Type II: Hypomanic episodes + depressive episodes
 Patients can present to the hospital in either spectrum of the disorder
 Initial treatment consists of
1. Managing the acute symptoms
2. Maintenance therapy with a mood stabilizer
 Lithium is a mood stabilizer shown to prevent suicides in patients with BP and is
often a drug of choice if the patient has good renal function and can be compliant
with salt and water intake
 Divalproex/Valproic acid are also first line therapy

MOOD STABILIZERS
BRAND ADVERSE EFFECTS AND
GENERIC NAME DAILY DOSE (MG) INDICATIONS
NAME COMMENTS
Lithium Carbolith® 300 – 1800 - Bipolar disorder - ADEs: Weight gain, GI upset,
Duralith® - Neuropathic pain polyuria, polydipsia, fine
- Migraine prophylaxis tremor, ↑ WBC,
hypothyroidism, ↑ potassium &
calcium
- Therapeutic range 0.6 to 1.0
umol/L (maintenance) or 0.8 to
1.2 umol/L (acute mania)
- TOXICITY: flu-like
symptoms, drowsy, ataxia,
coarse tremor, arrhythmias,
myocarditis, seizures, coma,
death (↑ level by NaCl depletion)
Carbamazepine Tegretol® 200 BID – 800 - Bipolar disorder - GI upset, CNS slowing, rash,
- Depression decreased WBC
- Neuropathic pain - Rare: aplastic anemia, LFTs,
- Seizures hyponatremia, SLE
- Migraine prophylaxis - Therapeutic range 14 to 54
umol/L
Divalproex Epival® 250 BID – 500 TID - Bipolar disorder - GI upset, CNS slowing,
- Depression alopecia, weight gain,
- Neuropathic pain
- Seizures - Rare: thrombocytopenia,
- Migraine prophylaxis decreased WBC, hepatotoxicity
- Therapeutic range 350 to 830
umol/L

Valproic acid Depakene® 250 BID- 500 TID Same as divalproex -Same as divalproex above
except that valproic acid
generally has more GI side
effects

-Divalproex and valproic acid

are not interchangeable
medications
Prepared by Tasha Ramsey B.ScPhm, ACPR, PharmD student 2012 and Katelyn Halpape BSP, ACPR, PharmD student 2015
Adapted with permission from Gillian Lagnado B Sc Phm (Hons) PharmD BCPP
St Paul’s Hospital, Vancouver BC Canada
 MOOD STABILIZERS CONTINUED

BRAND ADVERSE EFFECTS AND

GENERIC NAME DAILY DOSE (MG) INDICATIONS
NAME COMMENTS
Lamotrigine Lamictal® Initial: -Bipolar depression -GI Nausea, chest pain,
Week 1-2: 12.5 – -Bipolar disorder peripheral edema, somnolence,
25 mg BID (maintenance) dysmenorrhea, dyspepsia,
Week 3-4: -Depression nystagmus,
25-50 mg BID (adjunctive)
>Wk 4: ↑ daily -Neuropathic pain -Rare: Risk of SJS if titrate too
dose by 50mg/day -Seizures quickly or with divalproex,
Usual: 112.5-187.5 -Migraine prophylaxis aseptic meningitis, neutropenia,
mg BID leukopenia, pancytopenia,
aplastic anemia, PRCA

Therapeutic Range: No
established level. Plasma [] of
0.25-0.29 mcg/mL have been
reported.
-
Quetiapine Seroquel® Initial for acute -Bipolar Depression Sedation, hypotension during
mania or -Bipolar titration (better with XR
maintenance (maintenance) formulation, agitation, prolongs
therapy: 400–800 -Psychosis (higher QTc, metabolic effects. See
mg/day. For doses) Antipsychotics section.
depression, 300– -Sedation (low doses)
600 mg/day -Depression
(intermediate doses)

Gabapentin Neurontin® 100 mg HS – 400 -Little effect as mood Drowsiness, dizzy, ataxia, N/V,
mg BID stabilizer blurred vision, tremor, slurred
-Seizures speech, weight gain
-Neuropathic pain
- Anxiolytic in severe Antacids decrease absorption
PD and social phobia by 20%
Topiramate Topamax® 25 mg HS – 100 -Seizures Weight loss (4kg), nausea,
mg BID -Migraine prophylaxis dizzy, tremor, ataxia, cognitive
dysfunction, headache,
paresthesias, sedation, fatigue,
diarrhea, nephrolithiasis,
glaucoma

Pregnancy: most agents have teratogenic risk, the risk increases if patient is on multiple medications (aim for
monotherapy), decrease serum concentration, try to avoid in 1st semester but must balance risk to mother/fetus
of uncontrolled bipolar vs. risk of medications
- Lithium: Ebstein’s anomaly 0.1%
- Carbemazepine: malformation < 5%, ? cleft palate, spina bifida
- Divalproex: heart defect & spina bifida 10.7 vs 2.9% in control group
- Lamotrigine: not teratogenic in animal, but increased risk of fetal death, DOC in pregnancy

Prepared by Tasha Ramsey B.ScPhm, ACPR, PharmD student 2012 and Katelyn Halpape BSP, ACPR, PharmD student 2015
Adapted with permission from Gillian Lagnado B Sc Phm (Hons) PharmD BCPP
St Paul’s Hospital, Vancouver BC Canada