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Mirtazapine adverse effects — MRCPsych Paper A MCQ

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ModeratePsychopharmacologyMirtazapine adverse effectsMRCPsych Paper A

A 30-year-old woman with major depressive disorder, reduced appetite and initial insomnia starts mirtazapine. Her mood and sleep improve, but she develops marked daytime somnolence, increased appetite and weight gain. Which receptor action of mirtazapine most directly explains the somnolence and best fits this adverse-effect profile?

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Correct answer: D — Histamine H1 receptor antagonism

The correct answer is D, histamine H1 receptor antagonism. Mirtazapine has prominent H1-antagonist activity, which directly accounts for its sedative effect; somnolence, increased appetite and weight gain are characteristic adverse effects. Weight gain may be multifactorial, but the combined clinical profile is strongly antihistaminergic. Adrenergic α2 antagonism increases noradrenergic and serotonergic transmission and contributes primarily to antidepressant action. Blockade of 5-HT2 receptors is also part of mirtazapine's serotonergic pharmacology but does not most directly explain sedation. Mirtazapine has little clinically significant muscarinic activity and does not act through dopamine D2 blockade.

Reference: Electronic Medicines Compendium (eMC), Mirtazapine 30 mg Tablets, Summary of Product Characteristics, sections 4.8 and 5.1, revised 2024. https://www.medicines.org.uk/emc/product/535/smpc