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Antipsychotic metabolic effects — MRCPsych Paper A MCQ

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HardPsychopharmacologyAntipsychotic metabolic effectsMRCPsych Paper A

A 45-year-old man with schizophrenia and type 2 diabetes has remained psychiatrically stable on olanzapine. Over 9 months he has gained 11 kg, his HbA1c has increased from 53 mmol/mol to 72 mmol/mol, and his triglyceride concentration has risen despite appropriate diabetes and lifestyle management. Following shared decision-making, olanzapine is cross-titrated to lurasidone. Which comparative property most directly supports selecting lurasidone in this situation?

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Reveal the answer and explanation

Correct answer: C — It has lower liability for weight gain, dyslipidaemia and dysglycaemia

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

D is correct. Olanzapine has a high liability for clinically significant weight gain and adverse changes in glucose and lipid parameters, whereas lurasidone has a substantially more favourable average metabolic profile. This makes lurasidone a rational alternative when diabetes control and weight have deteriorated, although metabolic monitoring must continue because its risk is not zero. Strong H1 antagonism generally promotes sedation, appetite and weight gain rather than reducing them. Muscarinic M3 antagonism can impair, not enhance, insulin secretion. Lurasidone neither induces nor depends on CYP1A2; it is primarily metabolised by CYP3A4. It is also not predominantly excreted unchanged by the kidneys, and renal elimination would not in itself prevent receptor-mediated metabolic adverse effects.

Reference: electronic Medicines Compendium. Lurasidone 18.5 mg film-coated tablets, SmPC sections 4.4, 5.1 and 5.2, revised 2026; and ZYPREXA coated tablets, SmPC sections 4.4 and 4.8, revised 2026. https://www.medicines.org.uk/emc/product/100737/smpc ; https://www.medicines.org.uk/emc/product/15470/smpc