Clozapine is indicated for: Refractory psychoses, Psychotic patients with severe extrapyramidal symptoms with other treatments, Psychotic patients with severe tardive dyskinesia with other treatments, Schizophrenia in patients unresponsive to conventional antipsychotic drugs, Psychosis in Parkinson’s disease.

Atypical neuroleptic drugs

Clozapine is a dibenzodiazepine derivative and an atypical antipsychotics prototype. Its therapeutic efficacy is proposed to be mediated through antagonism of the D₂ and 5-HT_2A receptors. It also acts as an antagonist at α-adrenergic, histamine H₁, cholinergic and other dopaminergic and serotonergic receptors.

Schizophrenia:

• Adult: 12.5 mg 1-2 times on day 1 followed by 25 mg 1-2 times on day 2, increased gradually in increments of 25-50 mg up to a daily dose of 300 mg within 14-21 days. Subsequent increments of 50-100 mg may be made 1-2 times wkly. Usual dose: 200-450 mg daily. Max: 900 mg daily.
• Elderly: ≥60 yr Initially, 12.5 mg on day 1 increased subsequently in increments of 25 mg daily.

Psychoses in Parkinson’s disease:

• Adult: Initially, 12.5 mg at bedtime, increased in increments of 12.5 mg up to twice wkly, not >50 mg daily at the end of the 2nd wk. Usual dose: 25-37.5 mg daily. Max: 100 mg daily.

Olanzapine may antagonize the effects of levodopa and dopamine agonists. Drugs that induce CYP1A2 or glucoronyl transferase enzymes e.g, Omeprazole and Rifampicin, may increase Olanzapine clearance. Inhibitors of CYP1A2 may potentially inhibit Olanzapine elimination. Carbamazepine may increase the clearance of Olanzapine. Concomitant administration of activated charcoal reduces the oral bioavailability of Olanzapine by 50-60%. Caution should be taken when Olanzapine is administered with centrally acting drugs and alcohol.

Severe cardiac disorders (e.g. myocarditis); renal impairment (avoid if creatinine clearance less than 10 ml/minute); history of neutropenia or agranulocytosis; bone-marrow disorders; paralytic ileus; alcoholic and toxic psychoses; history of circulatory collapse; drug intoxication; coma or severe CNS depression; uncontrolled epilepsy; breast-feeding.

Common side effects are constipation, dizziness or lightheadedness (mild), drowsiness, headache (mild), increased watering of mouth, nausea or vomiting, unusual weight gain. Less common side effects include abdominal discomfort or heartburn, dryness of mouth.

Pregnancy Category B. Clozapine can be used in pregnancy if the physician feels that it is necessary. There are no adequate studies of Clozapine in pregnant women. Studies in animals suggest no important effects on the fetus.

Animal studies suggest that Clozapine is secreted in breast milk. Therefore, women taking Clozapine should not nurse their infants.

Patient with risk factors for stroke, history of long QT syndrome, history of seizures or conditions that lower the seizure threshold, history of cardiac impairment or abnormal cardiac findings on examination, benign prostatic hyperplasia, angle-closure glaucoma, history of colonic disease or lower abdominal surgery. Avoid abrupt withdrawal. Elderly with dementia-related psychosis. Hepatic or mild to moderate renal impairment. Pregnancy and lactation.

Symptoms: Drowsiness, lethargy, areflexia, coma, confusion, hallucinations, agitation, delirium, extrapyramidal symptoms, hyperreflexia, convulsions; hypersalivation, mydriasis, blurred vision, thermolability; hypotension, collapse, tachycardia, cardiac arrhythmias; aspiration pneumonia, dyspnoea, resp depression or failure.

Management: Symptomatic and supportive treatment. Establish and maintain airway, and ensure adequate ventilation and oxygenation. Gastric lavage and/or administration of activated charcoal w/in the 1st 6 hr after the ingestion. Close medical supervision is needed for at least 5 days due to the possibility of delayed reactions.

Store between 15-30°C.