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.
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