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Amisulpride Augmentation — MRCPsych Paper B MCQ

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ModerateSchizophrenia & PsychosisAmisulpride AugmentationMRCPsych Paper B

A 50-year-old man with treatment-resistant schizophrenia has persistent positive symptoms despite 6 months of adherent clozapine treatment at the maximum tolerated dose. His stable trough clozapine concentration is 0.55 mg/L. Substance misuse, relevant physical illness, interacting medication and an affective psychosis have been excluded, and appropriate psychological treatment has been offered. Which statement about augmenting clozapine with amisulpride is most accurate?

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Correct answer: C — Evidence of efficacy is limited; if used, amisulpride should be a time-limited, closely monitored individual trial

Explanation lettering: C = shown as A · E = shown as B · B = shown as C · A = shown as D · D = shown as E

B is correct. NICE allows consideration of a second antipsychotic only after clozapine has been optimised and reversible causes of apparent non-response have been addressed. It does not recommend amisulpride specifically. In the UK AMICUS placebo-controlled trial, amisulpride did not produce a statistically significant improvement in the primary response outcome and caused a greater adverse-effect burden, including cardiac effects. Therefore, its use should be an explicitly documented, time-limited trial with assessment of target symptoms, adverse effects and ECG-related risk. A overstates efficacy and understates monitoring. C incorrectly attributes a drug-specific recommendation to NICE. D confuses persistent psychosis with an indication for antidepressant treatment. E is wrong because a therapeutic concentration supports adequate exposure but does not itself exclude non-adherence patterns, comorbidity, substance misuse or other causes of pseudo-resistance.

Reference: Barnes TRE et al. Amisulpride augmentation in clozapine-unresponsive schizophrenia (AMICUS): a double-blind, placebo-controlled, randomised trial of clinical effectiveness and cost-effectiveness. Health Technology Assessment. 2017;21(49). https://pubmed.ncbi.nlm.nih.gov/28869006/