The Basics of Clinical The Basics of Clinical Psychopharmacology:Psychopharmacology:Mood StabilizersMood Stabilizers

Edition 2, Lecture 2

ASCP Model Curriculumfor

Medical Students

AuthorAuthor

Eric Peselow, MDEric Peselow, MD

Research ProfessorResearch Professor

NYU School of MedicineNYU School of Medicine

Objectivesfrom ADMSEP Psychiatry Learning

Objectives Taskforce, 2007

By completion of the By completion of the clerkship/medical school, the student clerkship/medical school, the student will be able to:will be able to:

ADMSEP Objectives—con’t

1. 1. Discuss the common, currently available psychotropic Discuss the common, currently available psychotropic medications with regard to clinical indications and medications with regard to clinical indications and contraindications, presumed mechanism of action and contraindications, presumed mechanism of action and relevant pharmacodynamics, common and serious relevant pharmacodynamics, common and serious adverse effects, pharmacokinetics, evidence for adverse effects, pharmacokinetics, evidence for efficacy, cost, risk of drug-drug interactions and drug-efficacy, cost, risk of drug-drug interactions and drug-disease interactions, and issues relevant to use in disease interactions, and issues relevant to use in special populations (e.g., pregnancy and lactation, special populations (e.g., pregnancy and lactation, childhood and adolescence, the elderly, persons using childhood and adolescence, the elderly, persons using herbal and over-the-counter treatments).herbal and over-the-counter treatments).

2. Propose selected psychotropic pharmacotherapy for 2. Propose selected psychotropic pharmacotherapy for designated patients and provide clinical reasoning that designated patients and provide clinical reasoning that includes discussion of factors influencing treatment includes discussion of factors influencing treatment selection (e.g.,patient-specific and drug-specific selection (e.g.,patient-specific and drug-specific variables, scientific evidence). variables, scientific evidence).

ADMSEP Objectives—con’t

3. Discuss the factors relevant to implementing, 3. Discuss the factors relevant to implementing, monitoring and discontinuing psychotropic monitoring and discontinuing psychotropic pharmacotherapy including drug dosing, treatment pharmacotherapy including drug dosing, treatment duration, and adherence, and make management duration, and adherence, and make management recommendations for dealing with an unsuccessful recommendations for dealing with an unsuccessful treatment trial (e.g., lack of efficacy, intolerability).treatment trial (e.g., lack of efficacy, intolerability).

4. Counsel patients about psychotropic 4. Counsel patients about psychotropic pharmacotherapy including risks and benefits of pharmacotherapy including risks and benefits of recommended treatment, treatment alternatives, recommended treatment, treatment alternatives, and no treatmentand no treatment

5. Identify and discuss resources to maintain an up-to-5. Identify and discuss resources to maintain an up-to-date knowledge of psychotropic pharmacotherapy date knowledge of psychotropic pharmacotherapy

ADMSEP Objectives—con’t

6. 6. Discuss special issues and concerns related to specific Discuss special issues and concerns related to specific psychotropic drug classes including metabolic, psychotropic drug classes including metabolic, hematologic, hepatic, etc.hematologic, hepatic, etc.

ADMSEP Objectives—con’t

6. 6. Discuss special issues and concerns related to specific Discuss special issues and concerns related to specific psychotropic drug classes including metabolic, psychotropic drug classes including metabolic, hematologic, hepatic, etc.hematologic, hepatic, etc.

Mood Stabilizing Agents:Mood Stabilizing Agents: Be able to discuss the risks, Be able to discuss the risks, early detection, relevance and interventions for adverse early detection, relevance and interventions for adverse drug effects of lithium, anticonvulsants, and selected drug effects of lithium, anticonvulsants, and selected antipsychotic drugs used as “mood stabilizers” (e.g., antipsychotic drugs used as “mood stabilizers” (e.g., Stevens-Johnson syndrome, hepatitis, electrolyte Stevens-Johnson syndrome, hepatitis, electrolyte disturbance, etc) and the relevance of laboratory tests disturbance, etc) and the relevance of laboratory tests including plasma level monitoring.including plasma level monitoring.

Objectives for This Lecture (MSII)

At the end of this lecture, the student will:At the end of this lecture, the student will:

Be able to articulate the basic mechanism of action of Be able to articulate the basic mechanism of action of the mood stabilizing drugsthe mood stabilizing drugs

Be able to name the basic drugs in this class and their Be able to name the basic drugs in this class and their clinical indicationsclinical indications

Objectives for This Lecture (MSIII)

At the end of this lecture, the student will:At the end of this lecture, the student will:

Be able to list appropriate dose ranges for at least 3 Be able to list appropriate dose ranges for at least 3 drugs in this classdrugs in this class

Be able to elucidate the major side effects seen in the Be able to elucidate the major side effects seen in the use of mood stabilizing drugsuse of mood stabilizing drugs

Outline

Definition of the disorder (with DSM criteria)Definition of the disorder (with DSM criteria)

Review of the basic science of the drug classReview of the basic science of the drug class

Medications used to treat bipolar disorderMedications used to treat bipolar disorder

The clinical psychopharmacologyThe clinical psychopharmacology

Classification of Bipolar Disorder

Summary of DSM-IV-TR Classification of Bipolar Disorders

* Symptoms do not meet criteria for manic and depressive episodes.

First, ed. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text Rev. Washington, DC: American Psychiatric Association; 2000:345-428.

At least 2 years of numerous periods of hypomanic and depressive symptoms*

One or more manic or mixed episodes, usually accompanied by major depressive episodes

Bipolar features that do not meet criteria for any specific bipolar disorders

One or more major depressive episodes accompanied by at least one hypomanic episode

Bipolar DisorderNot Otherwise

SpecifiedCyclothymicBipolar IIBipolar I

Abnormally and persistently elevated, expansive, or irritable mood for at least 1 week*

Inflated self-esteem or grandiosity Decreased need for sleep Pressured speech Flight of ideas or racing thoughts Distractibility Increase in goal-directed activity or psychomotor

agitation Excessive involvement in pleasurable activities that

have a high potential for painful consequences

First, ed. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text Rev. Washington, DC: American Psychiatric Association; 2000:345-428.

* This symptom must be present.

Summary of DSM-IV-TR Criteria for Manic Episodes in Bipolar Disorder

Depressed mood* Markedly diminished interest or pleasure* Significant weight loss or gain or appetite increase or

decrease Insomnia or hypersomnia Observable psychomotor agitation or retardation Fatigue or loss of energy Feelings of worthlessness or excessive or inappropriate guilt Diminished ability to think, concentrate, or make decisions Recurrent suicidal ideation, thoughts of death, a suicide

attempt, or a specific plan for committing suicide* At least one of these symptoms must be present.

First, ed. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text Rev. Washington, DC: American Psychiatric Association; 2000:345-428.

Summary of DSM-IV-TR Criteria for MajorDepressive Episodes in Bipolar Disorder

Bipolar Epidemiology Lifetime prevalence (adults)

Bipolar I 0.8-1.6% Bipolar II 0.5-5.5% (Both may be underestimates)

Age of onset Mean age 21 years Peak age 15-19 years

Gender Bipolar I male = female Bipolar II female > male

Bipolar Disorder Has Serious Consequences

Impaired functioning Disrupted relationships Increased mortality (2-2.5 times) High suicide rate (19%) Financial disasters Alcohol and other substance abuse

JAMA. 1990 (Nov. 21)

ECA ECA StudyStudy

Lifetime Prevalence ofSubstance Dependence/Abuse in Selected Mood Disorders

Bipolar I 61% Bipolar II 48% Major depression 27%

FDA-Approved

Acute Mania

1970 Lithium 1973 Chlorpromazine 1995 Divalproex 2000 Olanzapine 2003-2004 Risperidone

ZiprasidoneAripiprazoleQuetiapine

First Manic EpisodePreferred Initial Strategies

Psychotic mania

Mood stabilizer + antipsychotic

Euphoric, dysphoric or mixed mania

Mood stabilizer

Hypomania

Mood stabilizer

Expert Consensus Guidelines. Post Grad Med 4/00

Acute Mania: First-Line

Severe

Li or Valproate + antipsychotic Less severe

Li or Valproate or antipsychotic

“Some evidence suggests a greater efficacy of

valproate compared with lithium in the treatment of

mixed states.”

APA Bipolar Guidelines, Revised 2002

Lithium Carbonate

C

O

Li

O

O

Li

FDA ApprovedLithium Indications

Acute Mania

Maintenance in bipolar disorder

Lithium

Pharmacokinetics Lithium is an element and the lightest of the alkali

metals. (Group 1A of the Periodic Table)

After ingestion, lithium is completely absorbed by the GI tract.

Serum levels peak in 0.5-2.0 hours for standard preparations and 4-4.5 hours for slow release (Lithobid) and controlled release (Eskalith CR) preparations.

Lithium Pharmacokinetics—con’t

Lithium does not bind to plasma proteins & is distributed non-uniformly throughout the body.

The half-life of lithium is 20 hours & equilibrium is reached after 5-7 days of regular intake.

Lithium is almost entirely eliminated by the kidneys.

Lithium is excreted in the breast milk and in insignificant amounts in the feces and sweat.

Lithium Pharmacodynamics

The therapeutic mechanism of action of lithium remains uncertain.

At present it is felt that lithium blocks the enzyme-inositol-1-phosphatase within neurons. That inhibition results in decreased cellular responses to neurotransmitters that are linked to the phosphatidylinositol second messenger system.

Lithium also inhibits glycogen synthase kinase decreasing levels of protein kinase C isoenzymes.

Lithium

Indications for Lithium use Bipolar disorder

Short term acute response is 70-80% based on double-blind studies.

Lithium maintenance is felt to decrease the number of recurrent affective episodes by at least 50% and the recurrences that do occur are less severe.

Schizoaffective disorder

Lithium

Indications for Lithium use—con’t Depressive Disorders

Studies show it is as good as antidepressants (tricyclics) and better than placebo as prophylaxis against recurrent cyclical episodes.

Lithium is used as adjuvant in partially responsive acute depression when added to tricyclic, SSRI, or MAOI. May be helpful in acute phase of bipolar depression.

Lithium

Indications for Lithium use—con’t Schizophrenia Impulse control disorders

Episodic rage in intermittent explosive disorder and mental retardation are reduced.

Other disorders Premenstrual dysphoric disorder, bulimia, binge

alcohol use, behaviors in cluster B personality disorders (aggressive or self-injurious) conduct disorder, PDD, MR.

Lithium

Clinical guidelines Lithium at this time is still considered to be

the drug of choice in bipolar illness and should be used unless there is a specific reason not to use it and/or a specific reason to use another drug.

Initial Workup for Lithium

Complete physical exam and “routine” laboratory tests, including: Serum creatinine (24 hour urine creatinine if there

is reason to be concerned about renal status) Electrolyte screen-SMA-6 Thyroid function tests-Total serum thyroxine

concentration-T4, resin triiodothyronine uptake (T3RU), free T4 index and thyroid stimulating hormone (TSH)

Complete blood count EKG (definite if patient is over 40) Pregnancy test if there is any suspicion of

pregnancy

Lithium Initial Management Start at 300 mg bid for 1-2 days and increase

to 300 mg tid for the rest of first week. Adjust upward to a range of 0.8-1.2 mEq/L

(some say 0.9-1.4 mEq/L) to control acute manic symptoms. Check level after 5 days on stable level.

Lithium level should be drawn 9-12 hours after the last dose to achieve best accuracy.

Lithium levels should be monitored Weekly for the first month Monthly for months 2 and 3 Every 2-3 months thereafter

Lithium Initial Management—con’t

Patients should be advised that changes in the body’s water and salt content can effect the way lithium is excreted, and so can increase or decrease serum lithium levels. Excessive intake of sodium lowers lithium levels Too little sodium (secondary to fad-diet or

antihypertensives) increases lithium levels Decreases in body fluid (excessive sweating) can

lead to dehydration and lithium intoxication

Lithium Initial Management—con’t

The therapeutic trial of lithium should last 4-6 weeks. (Note: lithium takes 2-4 weeks to work)

If the patient is manic and highly active, in the first 1-3 weeks it is often necessary to decrease the motor overactivity with other agents. These agents include: typical and atypical antipsychotics, divalproex, carbamazepine, and benzodiazepines.

Lithium Initial Management—con’t Atypical antipsychotics (risperidone 4-6 mg or

olanzapine 10-20 mg)

Typical antipsychotics are used less frequently due to side effects (e.g., EPS and tardive dyskinesia) but are still an effective strategy.

Lithium Initial Management—con’t Carbamazepine or valproate are alternatives to

lithium. Sedative effects decreases motor activity. Valproate can be loaded up to 1500 mg/day by day 4-6 if needed. Often the combination of lithium + anticonvulsant gives the best result.

Benzodiazepines: lorazepam (1 mg, up to 6 mg/day or more) and clonazepam (1-8 mg/day) often control over activity and help with sleep. (Note: these upper limits are NOT used in most other circumstances.)

Lithium Initial Management—con’t

If lithium if effective after 4-6 weeks, one can slowly discontinue the above adjuvant drugs over 1-3 months.

Patient should be continued on lithium for at least another 9-24 months.

Lithium Initial Management—con’t If lithium is not successful in controlling acute mania

(after raising serum levels to 1.4mEq/L) one may either taper & discontinue the drug (giving another agent) or more practically lower Li (to 600-900 mg/day, blood level 0.6-0.8mEq/L) & add carbamazepine or valproate.

A practical regimen would be lithium (achieving level of 0.8mEq/L) & valproate 1000-1500 mg/day (level 50-100ng/ml) or carbamazepine 600-1000 mg/day (level 6-10ug/ml).

Lithium Maintenance

Decision for long-term treatment is based on severity of affective illness, quality of patient’s support system and long-term medication risk.

Appropriate prophylactic levels are 0.6-1.0 (level above 0.8 should be tried before Li is considered a failure) with 0.4 as absolute minimum. 6-12 month check of serum creatinine and TSH is required

Lithium Response Rates

Rapid Dysphoric History of (-) Family >3 cycling mania substance history episodes

abuse

70%} Nonrapid Euphoric No (+) Family Few cycling mania substance history lifetime

abuse episodes

MD

}30%

MD

Long-Term Lithium Maintenance(n=360, average duration 6 years)

Complete remission 29% 50-90% improved 36% Poor outcome not related to psychotic,

mixed, rapid cycling, or episode sequence

Tondo et al. BJP 2001;178(suppl 41):184-190

Expert Consensus Guideline. J Clin Psychiatry. 1996;57(suppl 12A)

Long-Term Prophylaxis inBipolar I Disorder

After 2 manic episodes Always

After 1 manic episode if: Usually Very severe or Strong family history

After 1 manic episode Sometimes

Lithium Side Effects Cognitive Tremor Gastrointestinal Endocrine

Thyroid Parathyroid

Weight gain Skin Renal Toxicity

Serum Lithium Levels

Increased Not Changed Decreased

Thiazides Amiloride (?) Acetazolamide

NSAIDs Furosemide Mannitol

ACE inhibitors Aspirin Aminophylline

Low sodium diet Sulindac Theophylline

Dehydration Caffeine

Elderly Mania

Renal disease Pregnancy

NA+

CH2CH2CH3CH3CH2CH2 CH

C

C

O

HO

O

O-

CH3CH2CH2 CH2CH2CH

3

CH

Divalproex Sodium

Valproate Indications

Epilepsy Acute mania Migraine prophylaxis

Role Acute and prophylactic treatment

of bipolar disorder

Valproate

Half-life: 6-16 hours Protein binding: >90% Dosing in mania

Initial: 250 mg tid or oral loading (20-30 mg/kg)Maintenance: serum conc = 50-125 g/ml

Once/day formulation available

Valproate Mechanism of Action

The mechanism is truly unknown, but there are clues:Valproate inhibits histone deacetylase,

resulting in phosphorylation-induced inactivation of glycogen synthase kinase–3 (GSK-3). GSK-3 affects neuroprotection and circadian rhythms, by which valproate, as well as lithium, may control manic symptoms.

Valproate Mechanism of Action

Additionally, valproate activates extracellular signal–regulated kinase (ERK).

Since inhibition of ERK causes manic-like activation in mice, this second possibly relevant pharmacodynamic action may contribute to antimanic actions.

Valproate

Black box warningsHepatotoxicityTeratogenicityPancreatitis

MonitoringBlood levelsCBC, platelets, LFTs

Valproate Side Effects

Cognitive (uncommon)

Tremor Gastrointestinal Weight gain Hair loss

Hepatotoxicity Pancreatitis Teratogenicity Polycystic ovaries (?)

Valproate Dosing

It is best to initiate treatment gradually, so as to minimize common adverse side effects such as nausea, vomiting and sedation. A severe manic state a patient can be valproate loaded; however, if treating a compliant inpatient: Day1: 250 mg bid Day 2-5: 250 mg tid Day 6-10: May raise to 250 mg bid and 500 mg qhs

as GI symptoms and sedation allow

Valproate Dosing—con’t

Further increases between 1250-2000 mg per day in divided doses may be needed. (500 mg bid & 1000 mg q hs)

Plasma level monitoring should be done 9-12 hours after the last dose.

Blood level monitoring for control of seizures is between 50 & 100ug/ml. For bipolar illness range should be 45-125ug/ml based on Bowden study. (JAMA1994)

At initiation of treatment , blood levels, along with CBC’s and LFT’s should be done weekly.

Valproate loading implies 20-30 mg/kg on day 1. (1500mg for a 70 kg individual)

Carbamazepine

N

CONH2

Carbamazepine

Indications Trigeminal neuralgia Epilepsy

Role Acute and prophylactic treatment of bipolar

disorder Adjunctive treatment with other mood

stabilizers

Carbamazepine Half-life

Initial: 25-65 hours Induced: 12-17 hours

Protein binding: 76% Metabolism

CYP3A4 Hepatic autoinduction10, 11-epoxide

Carbamazepine

Immediate and extended release

Dosing

Initial: 200-400 mg/day (divided)

Maintenance: serum conc = 4-12 g/ml

Carbamazepine Mechanism of Action CBZ's cellular actions with acute onset that

might parallel the time course of clinical anticonvulsant effects include:

decreasing sodium influx and glutamate release

increasing potassium conductance, and

acting on peripheral benzodiazepine and 2-adrenergic receptors.

Acute -aminobutyric acid type B (GABAB) receptor actions like those of baclofen may relate to the rapid onset of clinical analgesic effects.

Acute or subchronic actions such as increasing striatal cholinergic neurotransmission; decreasing adenylate cyclase activity stimulated by dopamine, norepinephrine, and serotonin; and decreasing turnover of dopamine, norepinephrine, and GABA may be pertinent to clinical antimanic effects.

Carbamazepine Mechanism of Action

Carbamazepine

Black box warningsAplastic anemia (1/100,000)

Agranulocytosis (1/100,000)

MonitoringBlood levels

CBC, platelets, LFTs

Carbamazepine Side Effects

Sedation Dizziness Ataxia Double/blurred vision GI distress

Hematopoietic suppression Hepatotoxicity (rare) Dermatologic Teratogenicity Hyponatremia

Carbamazepine Interactions

CBZ decreases levels of: Clonazepam, clozapine, olanzapine, haloperidol,

alprazolam, bupropion, oral contraceptives

CBZ levels increased by: Cimetidine, macrolides, fluoxetine, valproate,

isoniazid, verapamil, ketoconazole

A Partial Listing

Carbamazepine Treatment

Pretreatment workup should include general medical history & physical exam. Emphasis should be to see if there is a history of blood dyscrasias or liver disease.

Lab exam should include CBC with platelet count, LFT’s serum electrolytes & EKG

Initiation of Drug- For the acute inpatient

Start at 200 mg bid. For patients with hepatic disease or cardiac problems for whom drug is indicated may start 100 mg bid for 1-2 days, 100 mg AM & 200 mg q hs for 1-2 days & then increase to 200 mg bid.

Clinical situation determines how aggressively one goes from there. Might increase by 200 mg every 1-2 days until a range of 800-1200 mg/day is reached. If side effects develop, go slower (may reduce dose before trying to increase again).

Carbamazepine

Initiation of Drug- For the acute inpatient (con’t)

No appropriate blood levels have been established but the anticonvulsant range of 6-12 ug/ml (some say 4-12 ug/ml) is often used as a guide. The average dose range to treat acute mania is 1000 mg/day but in some cases doses up to 2200 mg/day are needed.

Carbamazepine

Olanzapine (Zyprexa)* Aripiprazole (Abilify)* Clozapine (Clozaril) Quetiapine (Seroquel)* Risperidone (Risperdal)* Ziprasidone (Geodon)*

*FDA approved

Atypical Antipsychotics for Mania

All antipsychotic drugs (except clozapine) have FDA approval for acute mania.

However the above statement is misleading in that many feel that antipsychotics decrease motor and verbal overactivity as opposed to direct manic ideation.

The atypical antipsychotics or even the typical antipsychotics are good adjuncts to the original mood stabilizers.

Atypical Antipsychotics for Mania

Other Mood Stabilizers

Topiramate

(Anticonvulsant. Not FDA approved for psychiatric disorders)

Main advantage in bipolar illness might be somnolence which can be achieved with as little as 25-50 mg/day.

The somnolence is often a problem in treatment as there is cognitive dulling.

Also may cause renal stones in 1-1.5% of patients, so they should drink plenty of water.

Topiramate (con’t)

Useful as an add-on to other agents in acute mania (and prophylactically), such as valproate.

Associated with weight loss. With valproate, associated with no further weight gain.

Carbamazepine and valproate reduce topiramate blood levels by 50% and 15% respectively.

Topiramate

Starting dose is 25 mg q day

Can raise at rate of 25 mg q d to an average range of 100-200 mg q day

Raise no faster than q 4-5 days

Maximum dose is 400 mg/day

Lamotrigine

(Anticonvulsant, FDA approved as prophylactic for bipolar disorder)

More effective for depression prophylaxis than is lithium, so may be helpful in bipolar II disorder.

In mania, more effective than placebo but not as effective as lithium/

Good drug for the depressed phase of bipolar illness. It does not seem to cause a switch into mania as most antidepressants can do.

Lamotrigine—con’t A good prophylactic combination is lithium

+ lamotrigine. Valproate and carbamazepine are rarely

used in combination with lamotrigine. Valproate raises lamotrigine levels so the rate

of dosage increase is 25 mg q 2 weeks. Carbamazepine decrease lamotrigine levels

so the rate of dosage increase is 50 mg q week

Lamotrigine—con’t

Average dose is 100-200 mg/day but can go up to 500 mg/day.

Initiate at 25 mg/week up to 100-200 mg range.

Big problem is the Stevens-Johnson rash (1 in 1000 in adults and 1 in 100 in children). Titrate slowly to avoid this. The actual rate of a lamotrigine rash is 8-10%.

Oxycarbazepine (OXZ)

Related to carbamazepine (CBZ), but does not have the enzyme-inducing effects of carbamazepine and at lower doses seems to be tolerated better. The overall level of drug interactions is less than with carbamazepine.

Comparison of OXZ to CBZ is 3:2 (1500 mg OXZ=1000mg CBZ)

Oxycarbazepine (OXZ) (con’t)

At doses of 1500 mg/day of oxcarbazepine, dizziness and ataxia occur at rate of 15-20%.

Oxcarbazepine is significantly more costly than carbamazepine.

There is less of a chance of blood dyscrasias with OXZ vs CBZ.

Oxycarbazepine (OXZ)(3)

Oxcarbazepine is usually started in the following manner (no faster):

Day 1: 150 mg bid Days 2-3: 300 mg bid Days 4-5 300 mg am and 600 mg hs Days 6-8 600 mg bid Can then increase up to 2400 mg/day

Pitfalls and Pearls

Pitfalls

Psychiatric medications are not benign, and mood stabilizers are no exception. Use of particularly lithium and the anticonvulsants require careful workup and monitoring.

When blood levels are indicated, they MUST be utilized for proper dosing.

Pitfalls and Pearls

Pearls As a rule of thumb, start low and titrate slowly. Use smaller doses for patients who are very sick. Use smaller doses for elderly patients. For treatment of acute mania, pick one or two

appropriate drugs and get to know them well. Use combinations of these drugs with great

caution.

Question 1

What is the major neurotransmitter thought to be responsible for the efficacy of antipsychotic drugs?

A. serotoninB. dopamineC. norepinephrineD. gamma-Aminobutyric acid E. none of the above

Question 2 What makes the “atypical antipsychotics”

atypical?

A. Different molecular structureB. Different pharmacokineticsC. Different metabolic pathwayD. Different side effect profileE. Different dosage schedule

Question 3 What neurological symptom is not caused

by the “typical” antipsychotics?

A. Tardive dyskinesia

B. Extra pyramidal symptoms

C. Acute dyskinesias

D. Pseudoparkinsonism

E. Expressive aphasia

Question 4

What would the best choice of antipsychotic be for a patient who has a lengthened QTc interval on EKG?

A. haloperidol

B. risperidone

C. thioridazine

D. olanzapine

E. quetiapine

Question 5 Which statement about clozapine is true?

A. It is the original antipsychotic drug

B. It can lead to death from agranulo-cytosis in up to 0.1% of patients

C. There is little prolactin increase

D. There is little weight gain

E. It binds only to the D1, D3, and 5HT1A receptors

Question 6 Which antipsychotic drug has the lowest

“potency”?

A. chlorpromazine

B. haloperidol

C. risperidone

D. aripiprazole

E. olanzapine

Answers to Questions

1. B

2. D

3. E

4. A

5. C

6. C

End of Lecture