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Clozapine Monitoring — MRCPsych Paper B MCQ

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HardSchizophrenia & PsychosisClozapine MonitoringMRCPsych Paper B

A 45-year-old man with treatment-resistant schizophrenia has taken clozapine 450 mg daily for 3 years. He recently stopped smoking cigarettes completely and switched to a nicotine-containing e-cigarette. On the same clozapine dose, his pre-dose trough clozapine concentration has risen from 0.42 mg/L to 0.95 mg/L. He reports increased sedation and has sinus tachycardia. There have been no missed or additional doses, changes in other medication or caffeine intake, or symptoms of intercurrent infection. What is the most likely explanation?

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Correct answer: D — Reduced hepatic metabolism following loss of tobacco smoke-mediated CYP1A2 induction

The correct answer is D. Clozapine is metabolised principally in the liver, importantly through CYP1A2. Polycyclic aromatic hydrocarbons in tobacco smoke induce CYP1A2; complete smoking cessation removes this induction, reducing clozapine clearance and raising its plasma concentration. Nicotine is not responsible, so switching to a nicotine-containing e-cigarette does not maintain the tobacco-smoke interaction. The marked trough-level rise with sedation and tachycardia is consistent with dose-related clozapine toxicity. Non-adherence is excluded by the dosing history and would not specifically explain the smoking-related change. Myocarditis is most strongly associated with early treatment and does not explain the increased clozapine concentration. Renal impairment is unlikely because clozapine undergoes extensive hepatic metabolism before excretion.

Reference: Clozapine Viatris 100 mg Tablets, Summary of Product Characteristics, sections 4.4, 4.5 and 5.2, revised February 2026. https://www.medicines.org.uk/emc/product/15498/smpc