Antipsychotics and Mood Stabilizers Pharmacokinetics Adverse Effects Drug Interactions Philip G Janicak MD Professor of Psychiatry Rush University Medical Center 1 Goals Antipsychotics Diagnostic indications Classification Relevant Pharmacokinetics Serious Adverse Effects Drug Interactions Mood Stabilizers Diagnostic indications Classification Relevant Pharmacokinetics Serious Adverse Effects Drug Interactions 2 Draft 3 27 07 1 Antipsychotics Diagnostic Indications Psychiatric Schizophrenia Schizoaffective disorder Mood disorders with psychosis Delusional disorder Nonpsychiatric Dementia Delirium Psychosis secondary to a non psychiatric medical disorder Developmental disability with psychosis and or aggression Tourette s disorder Nausea vomiting 3 Impact of Schizophrenic Symptoms on Overall Functioning Positive symptoms Delusions Hallucinations Disorganized speech Catatonia Negative symptoms Social Cognitive symptoms Work Attention Memory Executive functions Affective flattening Occupational Alogia Avolition Anhedonia Social inattentiveness Interpersonal Mood Selfcare Schneiderian First Rank Symptoms Draft 3 27 07 symptoms Dysphoria Suicidality Helplessness 4 2 Pharmacokinetics of Antipsychotics ADME profiles All are readily absorbed All are metabolized by the hepatic cytochrome P450 system T1 2 is generally 20 hours except prone to drug interactions ziprasidone quetiapine aripiprazole Dosing adjustment in elderly renal and or hepatic impairment 5 Antipsychotic Agents Class Trade Name Generic Name Dosage average range PO qd Thorazine Chlorpromazine 100 1000 mg Sparine Vesprin Promazine Triflupromazine 25 1000 mg 20 150 mg Mellaril Serentil Quide Thioridazine Mesoridazine Piperacetazine 30 800 mg 20 200 mg 20 160 mg Stelazine Prolixin Trilafon Tindal Compazine Trifluoperazine Fluphenzine Perphenazine Acetophenazine Prochlorperazine 2 60 mg 5 40 mg 2 60 mg 40 80 mg 15 125 mg Navane Taractan Thiothixene Chlorprothixene 6 60 mg 10 600 mg Loxitane Loxapine 20 250 mg Haldol Inapsine Haloperidol Droperidol 3 50 mg 2 5 10 mg IM Molindone 15 225 mg Phenothiazines Aliphatics Piperidines Piperazines Thioxanthenes Dibenzoxapines Butyrophenones Dihydroindolones Moban Janicak Draft 3 27 07 6 3 Antipsychotic Agents con t Class Trade Name Generic Name Dosage average range PO qd Clozapine 100 900 mg Risperidone Paliperidone 2 10 mg 3 12 mg Olanzapine 5 20 mg Quetiapine 75 750 mg Ziprasidone 40 160 mg Aripiprazole 10 30 mg Penfluridol 100 mg wk Pimozide 1 10 mg Dibenzodiazepines Clozaril Benzisoxazole Risperdal Invega Thienobenzodiazepines Zyprexa Dibenzothiazepines Seroquel Benzisothiazolyls Geodon Quinolinones Abilify Diphenytbutyrylpiperidines Semap Orap Janicak 7 Antipsychotics Adverse Effect Profiles EPS HPDL CLOZ RISP OLZ QTP ZIP ARIP Neurological 0 0 0 0 0 Weight gain Endocrine 0 0 Anticholinergic 0 0 0 0 0 0 Hematological 0 0 0 0 0 0 0 Cardiovascular 0 0 Prolactin 0 0 0 0 0 Sedation At appropriate doses 0 none mild moderate PALI substantial Adapted from Masand PS et al Handbook of Psychiatry in Primary Care 1998 8 Draft 3 27 07 4 ADVERSE EFFECTS OF ANTIPSYCHOTICS Acute EPS Maximum Minimum HIGH POTENCY FGAs RISPERIDONE OLANZAPINE PALIPERIDONE DOSE RELATED Psuedoparkinsonism CLOZAPINE ZIPRASIDONE QUETIAPINE ARIPIPRAZOLE Dystonia Akathisia Tardive Dyskinesia Based on clinical trial data 9 Dementia Patients Risks Mortality rate CVA in 4 vs 2 Risks may be higher for all APs Recommendations Avoid in those with vascular dementia Avoid with TIA hypertension Afib Use low doses Monitor for hypotension sedation EPS 10 Draft 3 27 07 5 Weight Gain Overview General population Increased morbidity and mortality Stigmatization Major mental disorders This adverse effect is more common with some recent antipsychotics Recognized problem since chlorpromazine Polypharmacy may contribute Divalproex sodium Lithium Antidepressants Antipsychotics Janicak 11 The Metabolic Syndrome Insulin resistance Hyperinsulinemia Decreased beta cell function Postprandial hyperglycemia 12 Draft 3 27 07 6 SGAs and Metabolic Abnormalities Weight Gain Risk for Diabetes Worsening Lipid Profile Clozapine Olanzapine Risperidone D D Quetiapine D D Aripiprazole Ziprasidone Drug increase effect no effect D discrepant results Newer drugs with limited long term data Diabetes Care 2004 13 Baseline Monitoring History personal or family of obesity diabetes dyslipidemia hypertension CVD BMI Waist circumference Blood pressure Fasting lipid profile Fasting plasma glucose 14 Draft 3 27 07 7 Anticholinergic Effects Most common with Clozapine Olanzapine Quetiapine Low potency FGAs Janicak 15 Hematological Clozapine induced agranulocytosis Management Stop agent Reverse isolation supportive measures GSCF filgastrim Rechallenging strategies Janicak Draft 3 27 07 16 8 Cardiovascular Related to both alpha1 adrenergic and muscarinic effects Hypotension Tachycardia Myocarditis Arrhythmogenic potential possible with all antipsychotics 17 Potential Consequences of QTc Interval Prolongation QTc prolongation Rarely Torsade de pointes arrhythmia syncope Rarely Ventricular fibrillation sudden death Royal College of Psychiatrists 1997 18 Draft 3 27 07 9 QT interval Time between onset of depolarization and repolarization Affected by diet alcohol intake time of day heart rate Usually corrected for heart rate QTc 19 Antipsychotics Drug Interactions Pharmacodynamic Anticholinergic Hypotension Pharmacokinetic P450 inhibition quinidine P450 induction carbamazepine 20 Draft 3 27 07 10 Bipolar Disorder Symptom Domains Mania Euphoria Grandiosity Pressured speech Impulsivity Excessive libido Recklessness Diminished need for sleep Manic depressed or mixed Depression Depression Anxiety Irritability Hostility Violence or suicide Cognition Racing thoughts Distractability Poor insight Disorganization Inattentiveness Confusion Psychosis Delusions Hallucinations Sensory hyperactivity 21 Mood Disorders Therapeutic Options Lithium A M First generation antipsychotics Anticonvulsants Pharmacological Somatic Valproate A Antidepressants OLZ FLU D Lamotrigine M Quetiapine D Carbamazepine A Electroconvulsive therapy Second generation antipsychotics Oxcarbazepine Possibly Clozapine Topiramate Gabapentin Bright light therapy Transcranial magnetic stimulation Vagal nerve stimulation Sleep deprivation Psychotherapy Cognitive behavioral therapy Marital family counseling Interpersonal therapy Group therapy Janicak Draft 3 27 07 Olanzapine A M Risperidone A Quetiapine A Ziprasidone A
View Full Document
Unlocking...