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Clozapine Augmentation — MRCPsych Paper B MCQ

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HardSchizophrenia & PsychosisClozapine AugmentationMRCPsych Paper B

A 41-year-old man with schizophrenia continues to experience distressing auditory hallucinations despite six months of adherent treatment with clozapine 700 mg daily. His trough clozapine concentration is 0.52 mg/L, substance misuse and relevant physical causes have been excluded, and appropriate psychological treatment has been offered. Following multidisciplinary review, amisulpride augmentation is being considered. Which dosing regimen corresponds to that evaluated in the UK AMICUS trial and is consistent with the UK licensed dose range for prominent positive symptoms?

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Correct answer: C — Initiate at 400 mg daily; maximum 800 mg daily

The correct answer is C. In the UK AMICUS trial, amisulpride was started at 400 mg daily for 4 weeks, with the option to increase to 800 mg daily thereafter. This also corresponds to the UK SmPC range for schizophrenia with prominent positive symptoms. Doses of 50–300 mg daily are principally associated with predominant negative symptoms, making A unsuitable. B does not reproduce the studied augmentation regimen and may provide insufficient postsynaptic D2/D3 blockade for persistent positive symptoms. Starting at 800 mg and escalating to 1200 mg is unnecessarily aggressive, particularly because clozapine may increase amisulpride exposure. Augmentation is permissible after clozapine optimisation, so E is incorrect. ECG/QTc, renal function, prolactin and extrapyramidal adverse effects require monitoring.

Reference: Barnes TRE et al. Amisulpride augmentation in clozapine-unresponsive schizophrenia (AMICUS), intervention regimen. Health Technology Assessment, 2017. https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/amisulpride-augmentation-in-clozapine-unresponsive-schizophrenia/