Psychiatry/Atypical antipsychotic (clozapine)

Clozapine

also: treatment-resistant schizophrenia · agranulocytosis

Overview

The most effective antipsychotic, reserved for treatment-resistant schizophrenia because of agranulocytosis — it requires mandatory blood monitoring.

Mechanism

A second-generation antipsychotic with relatively weak D₂ and strong 5-HT₂A blockade (+ many other receptors). Unusually effective but carries a unique toxicity profile.

Indications

Treatment-resistant schizophrenia (after ≥2 other antipsychotics failed)

Adverse effects

Agranulocytosis / neutropeniaserious

Mandatory FBC monitoring (weekly → fortnightly → monthly); stop if neutropenic.

Myocarditis / cardiomyopathyserious

Especially early — monitor troponin/ECG/symptoms.

Constipation → potentially fatal ileusserious

Treat constipation aggressively.

Seizures (dose-related), hypersalivation, weight gaincommon

Cautions & contraindications

Use without FBC monitoring / previous clozapine neutropeniaall

Agranulocytosis.

Missed doses >48 hall

Must re-titrate from low dose (lost tolerance).

Interactions

Smoking INDUCES clozapine metabolism — stopping smoking raises levels (toxicity); caffeine inhibits

Monitoring & kinetics

FBC (weekly 18 weeks → fortnightly → monthly); troponin/ECG (myocarditis); weight, glucose, lipids

Oral, slow titration. The "48-hour rule": re-titrate if doses missed.

Choosing it

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Source: BNF — Clozapine