Klozapin

Klozapin, commonly known as clozapine, is an atypical antipsychotic used to treat schizophrenia that has not responded adequately to other antipsychotic medications. It is especially noted for its efficacy in treatment-resistant cases and for reducing suicidality in schizophrenia.

Pharmacology and effects: Clozapine works as a multi-receptor antagonist, with high affinity for serotonin 5-HT2A and relatively lower D2 receptor occupancy compared with typical antipsychotics. This profile is associated with strong antipsychotic effects and a lower risk of extrapyramidal symptoms, but it carries a higher risk of metabolic side effects, weight gain, diabetes, and dyslipidemia. Its unique pharmacology also contributes to anti-suicide effects in schizophrenia.

Indications and use: It is approved for treatment-resistant schizophrenia and schizoaffective disorder in many countries, and is used to reduce suicidality in schizophrenia.

Monitoring and safety: Because of the risk of agranulocytosis and neutropenia, clozapine requires regular blood monitoring. In many systems, patients start with weekly blood counts for the first six months, then biweekly, then monthly. Additional monitoring includes blood pressure, heart rate, weight, glucose, lipids, and liver enzymes. Important adverse effects include agranulocytosis, myocarditis, seizures, constipation with potential ileus, sialorrhea, sedation, and orthostatic hypotension. Drug interactions, particularly with smoking (which induces CYP1A2) and various antidepressants, can affect clozapine levels.

Regulatory notes: Clozapine is prescription-only and is frequently subject to special monitoring programs to ensure safety. It remains a critical option for patients who have not benefited from other antipsychotics.