Pharmacology of Psychotherapeutic Drugs

By : Dr SeddighHUMS

Psychiatric Diagnoses

Diagnoses of Concern Mood Disorders Substance abuse related Somatoform Disorders Anxiety Disorders Psychotic Disorders Personality Disorders Impulse Control Disorders Factitious Disorders (Munchausen’s) Malingering

Critical Situations

Suicide risk v. accidental overdose Potential for violence toward others Multi-substance abuse Undiagnosed depression Opioids and benzodiazepines Poor impulse control

What is Multi-Axial Diagnosis? Axis I: Clinical Disorders & other conditions that

may be focus of attention Axis II: Personality Disorders, Mental

Retardation Axis III: General Medical Conditions Axis IV: Psychosocial and Environmental

Problems Axis V: Global Assessment of FunctioningAm Psychiatric Association, 2000. Quick Reference to the Diagnostic Criteria from DSM-IV-TR.

Washington, DC: APA Press.

Mood Disorders

Major Depressive Disorder Dysthymic Disorder Depressive Disorder (NOS) Bipolar

Psychotic Disorders

Psychotic Disorders

Schizophrenia Schizophreniform Schizoaffective Disorder Delusional Disorder Brief Psychotic Disorder

Pharmacology Basics

Classes of Psychiatric Drugs

Tricyclics & Tetracyclics

Selective Serotonin Reuptake Inhibitors

Monoamine Oxidase Inhibitors

“Atypical” antidepressants

Benzodiazepines

Nonbenzodiazepine anxiolytics

Antipsychotics “Atypical”

antipsychotics Lithium Antiepileptic drugs Stimulants Anti-EPS agents

Cyclic Antidepresants

Imipramine (Tofranil)

Desipramine (Norpramin)

Amitriptyline (Elavil) Nortriptyline

(Pamelor) Clomipramine

(Anafranil)

Trimipramine (Surmontil)

Doxepin (Sinequan) Protriptyline

(Vivactil) Amoxapine

(Asendin) Maprotiline

(Ludiomil)

Cyclic Antidepressant Indications

Generalized Anxiety Disorder Obsessive-Compulsive Disorder Panic Disorder with Agoraphobia Anorexia Nervosa &Bulimia Cataplexy & narcolepsy Depression Childhood enuresis Migraine & pain Urticaria & itching

Cyclic Adverse Effects

Weight gain Inducing mania Anticholinergic

dry mouth, constipation, blurred vision, urinary retention Sedation Autonomic

orthostatic hypotension, profuse sweating, palpitations, hypertension

Cardiac tachycardia, flattened T waves, prolonged QT intervals, depressed

ST segments Neurological

delirium, psychomotor stimulation, myoclonic twitches, tremors, paresthesias, peroneal palsies, ataxia

Selective Serotonin Reuptake Inhibitors

Citalopram (Celexa) Escitalopram (Lexapro) Fluoxetine (Prozac) Fluvoxamine (Luvox) Paroxetine (Paxil) Sertraline (Zoloft)

SSRI Indications

Depression & suicidality Obsessive-Compulsive Disorder Panic Disorder Eating Disorders Alcoholism Obesity

Features of Serotonin Syndrome Diarrhea Diaphoresis Tremor Ataxia Myoclonus Hyperactive reflexes Disorientation Rigidity

Uncontrollable shivering Hyperthermia Delirium Coma Status epilepticus Cardiovascular collapse Death

MAO Inhibitors

MAOI Indications

Atypical depression Major depression Dysthymia Melancholia Panic disorder Bulimia Atypical facial pain Parkinson’s Disease

Obsessive-compulsive

Narcolepsy Headache Chronic pain

disorder Generalized anxiety

MAO Inhibitor Drugs MAO A

Nonselective inhibitors Phenelzine (Nardil) Tranylcypromine (Parnate) Avoid tyramine-containing foods

MAO B Selective inhibitor Selegiline [deprenyl] (Eldepryl) Avoid tyramine and SSRIs Lose selectivity at high doses

MAO Inhibitor drug interactions Antidepressants

SSRIs

Tricyclic antidepressants

Sympathomimetics

Ephedrine

Some opioids

Meperidine

Pentazocine

Dextromethorphan

MAOI Dietary Interactions

Contain Tyramine Cheese Overripe aged fruit Fava beans Sausage, salami Sherry, liquors Sauerkraut MSG (glutamate)

Pickled fish Brewer’s yeast Beef & chicken liver Fermented products Red wine Caffeinated

beverages Chocolate

Medications to Avoid with MAOIs

Antiasthmatics Antihypertives (methyldopa, guanethidine) Buspirone Levodopa Opioids Cold, allergy or sinus medications with

dextromethorphan or sympathomimetics SSRIs, clomipramine, venlafaxine, sibutramine Sympathomimetics L-Tryptophan

Medications to Use Carefully with MAOIs

Anticholinergics Antihistamines Disulfiram Bromocriptine Hydralazine Sedative-hypnotics Terpin hydrate with codeine Tricyclics & tetracyclics

Atypical Antidepressants

Atypical Antidepressants

Buproprion (Wellbutrin, Zyban) Duloxetine (Cymbalta) Mirtazapine (Remeron) Nefazodone (Serzone) Trazodone (Desyrel) Venlafaxine (Effexor)

Atypical Antidepressant Indications

Depression Generalized Anxiety Disorder Obsessive-Compulsive Disorder Smoking Cessation Panic Disorder Agoraphobia Chronic pain

Atypical Antidepressant Adverse Effects and Problems

Buproprion: headache, insomnia, upper respiratory complaints, nausea, restlessness, agitation & irritability

Duloxetine: nausea, dry mouth, fatigue, dizziness, constipation, somnolence & sweating

Mirtazapine: somnolence, dizziness, increased appetite, increased cholesterol and triglycerides, orthostatic hypotension

Nefazodone: postural hypotension, activation of mania, liver dysfunction

Trazodone: sedation, orthostatic hypotension, dizziness, headache, nausea, priapism

Venlafaxine: nausea, somnolence, dry mouth, hypertension, dizziness, nervousness, constipation, etc.

Benzodiazepines

Benzodiazepines

Triazolam (Halcion) Alprazolam (Xanax) Lorazepam (Ativan) Oxazepam (Serax) Temazepam

(Restoril) Chlordiazepoxide

(Librium) Clonazepam

(Klonopin)

Diazepam (Valium) Clorazepate

(Tranxene) Halazepam

(Paxipam) Prazepam (Centrax) Flurazepam

(Dalmane) Estzolam (ProSom) Midazolam (Versed)

Benzodiazepine Indications

Sedative-hypnotics Muscle relaxants Anticonvulsants Alcohol withdrawal Anxiety disorders Agitation control

Nocturnal myoclonus

Tic douloureux Tetanus Cerebral malaria Chloroquine toxicity Maternal eclampsia

Nonbenzodiazepine Anxiolytics

Meprobamate (Miltown) Buspirone (Buspar) Gepirone (Ariza) Ipsapirone Tandospirone

Antipsychotics

Antipsychotics

Phenothiazines: Chlorpromazine (Thorazine), Fluphenazine (Prolixin), Mesoridazine (Serentil), Trifluoperazine (Stelazine), Perphenazine (Trilafon), Thioridazine (Mellaril)

Butyrophenones: Haloperidol (Haldol) Thioxanthenes: Thiothixene (Navane) Dihydroindolones: Molindone (Moban, Lidone) Dibenzoxazepines: Loxapine (Loxitane) Diphenylbutylpiperidines: Pimozide (Orap)

Antipsychotic Mechanisms D2 receptor antagonists 5HT2 receptor antagonists Older agents generally have higher

5HT/DA binding ratios The atypical antipsychotics have less

potential for extrapyramidal side effects (EPS)

Antipsychotic Indications

Acute Schizophrenia Chronic Schizophrenia Schizoaffective Disorders Depression with Psychotic Features Agitation Mania Chorea

Antipsychotic Adverse Effects Cardiac toxicity &

sudden death Orthostatic hypotension Hematological toxicity Increased secretion of

prolactin Sexual dysfunctions Weight gain Jaundice Dermatitis and

photosensitivitySadock BJ & Sadock VA, 2003. Kaplan & Sadock’s

Synopsis of Psychiatry 9th Ed. Philadelphia, PA: Lippincott Williams & Wilkins.

Neuroleptic-induced Parkinsonism

Neuroleptic-induced Acute Dystonia

Neuroleptic-induced Tardive Dyskinesia

Neuroleptic Malignant Syndrome

Lowered seizure threshold

Sedation Anticholinergic effects

Atypical Antipsychotics

Atypical Antipsychotics

Aripiprazole (Abilify) Clozapine (Clozaril) Olanzapine (Zyprexa) Quentiapine (Seroquel) Risperidone (Risperdal) Ziprazadone (Geodon)

Advantages of Atypical Antipsychotic Agents

These are serotonin-dopamine antagonists (except aripiprazole which is partial agonist for D2 receptors, but behaves as functional antagonist in hyper DA states & agonist in hypo DA states)

Lower risk for Extrapyramidal Side Effects (EPS) than DA antagonists

Effective for positive & negative symptoms Effective for treatment of mood disorders with

psychotic or manic features & for behavioral disturbances with dementia

Toxicities of Atypical Antipsychotic Agents

Aripiprazole: Too new to be fully known (mild nausea & vomiting, wt. loss, lowered prolactin levels, low levels of EPS)

Clozapine: sedation, dizziness, syncope, tachycardia, hypotension, ECG changes, leukopenia (aplastic anemia), wt. gain

Olanzapine: Somnolence, dry mouth, dizziness, constipation, dsypepsia, increased appetite & wt. gain, tremor

Quetiapine: somnolence, postural hypotension, dizziness, modest wt. gain

Risperidone: dose-dependent EPS, wt. gain, anxiety, nausea, erectile and orgasmic dysfunction

Ziprasidone: somnolence, headache, dizziness, nausea, QT prolongation (fatal in pts with Hx of cardiac arrhythmia)

Many cause abnormalities with glucose & lipid metabolism leading to DM & hyperlipidemias

Risk Factors Leading to Acute Dystonic Reactions

Male gender Younger age Previous dystonic reaction Using higher doses of medication Giving higher potency antipsychotics Intramuscular route of administration

Drugs to Treat ExtrapyramidalSide Effects

Benztropine (Cogentin) Trihexyphenidyl (Artane) Procyclidine (Kemadrin) Diphenhydramine (Benadryl) Biperiden (Akineton) Amantadine (Symmetrel)

Strategies for Extrapyramidal Side Effects (EPS) Reduce antipsychotic medication dose Substitute lower-potency antipsychotic Add an anticholinergic agent, titrate up Add amantadine to anticholinergic agent Add a benzodiazepine or beta-blocker Stop antipsychotic medication Substitute an atypical agent

Antimania Medications

Lithium Benzodiazepines Anticonvulsants

Carbamazepine (Tegretol)

Gabapentin (Neurontin)

Lamotrigine (Lamictal) Topiramate (Topamax) Valproate (Depakote);

valproic acid (Depakene)

Calcium Channel Antagonists

Amlodipine Isradipine Nicardipine Nifedipine Nimodipine Nisoldipine Verapamil

Atypical antipsychotic agents

Anticonvulsant Issues Carbamazepine: blood dyscrasias, hepatitis, exfoliative

dermatitis, GI upset, acute confusional state, decreased cardiac conduction, SIADH, birth defects

Gabapentin: somnolence, dizziness, ataxia, fatigue, nystagmus

Lamotrigine: decreased valproic acid level, increased carbamazepine epoxide metabolite, life-threatening skin rashes

Topiramate: increased phenytoin and valproic acid levels, psychomotor slowing, speech & language problems, dizziness, ataxia, fatigue, poor concentration, wt. loss, tremor

Valproate: GI distress, sedation, tremor, wt. gain, hair loss, elevated transaminases, fatal hepatotoxicity, platelet dysfunction

Sadock BJ & Sadock VA, 2003. Kaplan & Sadock’s Synopsis of Psychiatry 9th Ed. Philadelphia, PA: Lippincott Williams & Wilkins.

Responsiveness to Lithium Unfavorable

Borderline features Neuroticism Rapid cycling Mixed

manic/depressive Sx Substance abuse Psychosis Depression followed

by maniaSadock BJ & Sadock VA, 2003. Kaplan & Sadock’s

Synopsis of Psychiatry 9th Ed. Philadelphia, PA: Lippincott Williams & Wilkins.

Favorable Prior long-term response

to Lithium Classic euphoric or pure

mania Family history of bipolar

disorder Secondary mania Family history of

response to lithium Obsessional features Mania followed by

depression

Recognizing Lithium Toxicity GI (mild)

Vomiting Abdominal pain Dryness of mouth

Neurological (mild) Ataxia Dizziness Slurred speech Nystagmus Lethargy or excitement Muscle weakness

GI (moderate-severe) Anorexia

Neurological (mod-sev) Muscle fasciculations Clonic limb movements Hyperactive DTRs Choreoathetoid

movement Convulsions Delirium Stupor Coma Death

Stimulants

Stimulants

Cocaine Amphetamines

Amphetamine (Adderall) Dextroamphetamine (Dexedrine) Methamphetamine (Desoxyn)

Methylphenidate (Concerta, Ritalin) Modafinil (Provigil) Pemolin (Cylert)

Stimulant Indications

Narcolepsy Attention Deficit Hyperactivity Disorder Enhanced alertness and combat

readiness (military only) Unofficial uses:

Reversing opioid induced sedation Refractory depression Chronic pain Stroke

Psychopharmacological Treatment of Agitation Anticonvulsants Antipsychotics Benzodiazepines Beta-blockers Buspirone Lithium Serotoninergic antidepressants

Impediments to Adherence to Recommended Treatment

Excessively complex regimens Early onset & persistence of side effects Slow onset of beneficial effects Low apparent relapse risk experienced if

treatment is interrupted Psychosis, confusion, dementia, low

intelligence, impaired hearing or vision Lack of information & need for education Involvement of multiple clinicians

Conclusions

Medications play a vital role in the management of mental illness.

There is still a role for therapy, and working with families.

There is much to still learn about drug therapy for mental illness.

Keep studying and asking questions.

ReferencesSadock BJ & Sadock VA. Kaplan & Sadock’s

Synopsis of Psychiatry 9th Ed. Philadelphia, PA: Lippincott Williams & Wilkins. 2003

Am Psychiatric Association Quick Reference to the Diagnostic Criteria from DSM-IV-TR. Washington, DC: APA Press. 2000

Drugs for Pain. Hanley & Belfus, Philadelphia. Misc. chapters. 2003.