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Clozapine Seizures — MRCPsych Paper B MCQ

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HardSchizophrenia & PsychosisClozapine SeizuresMRCPsych Paper B

A 42-year-old man with treatment-resistant schizophrenia has two generalised tonic–clonic seizures while taking clozapine. A correctly timed trough clozapine concentration is 0.8 mg/L. Infection, metabolic disturbance, substance withdrawal, interacting medication and recent changes in smoking or caffeine intake have been excluded. After acute management, clozapine is restarted at a reduced dose because continuing it remains clinically essential, and long-term antiseizure prophylaxis is planned. According to current Maudsley-derived UK clozapine therapeutic drug-monitoring guidance, which antiseizure medication is preferred?

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Correct answer: D — Lamotrigine

Lamotrigine is preferred. Current clozapine therapeutic drug-monitoring guidance authored by Professor David Taylor identifies lamotrigine as the preferred antiseizure agent when prophylaxis is indicated; topiramate is an alternative and valproate should not normally be used. This patient is also under 55, so initiating valproate requires two specialists to document that no effective or tolerated alternative exists. The Clozaril SmPC additionally warns that valproate co-prescription may increase neutropenia and myocarditis risk. Carbamazepine must be avoided because its bone-marrow toxicity compounds clozapine-associated neutropenia and it induces clozapine metabolism. Phenytoin also induces clozapine metabolism, risking reduced antipsychotic efficacy. Levetiracetam is used for generalised seizures but is not the preferred agent in the cited clozapine-specific guidance. Lamotrigine requires slow titration because of serious rash risk, so appropriate interim risk management and neurological input may be necessary.

Reference: Taylor D. What to do with clozapine level results. Oxford Health NHS Foundation Trust; authored March 2025, updated September 2025: antiseizure-agent footnote. https://www.oxfordhealthformulary.nhs.uk/docs/Clozapine%20TDM%20poster%20-September%202025.pdf?UNLID=8335532822025109151439