Quetiapine sedation — MRCPsych Paper A MCQ

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ModeratePsychopharmacologyQuetiapine sedationMRCPsych Paper A

A 34-year-old man with bipolar depression starts quetiapine at night. During the first week, he develops marked morning drowsiness without postural dizziness or other adverse effects. Which receptor action principally explains this sedation?

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Correct answer: C — Histamine H1 receptor antagonism

The correct answer is C. Quetiapine has high affinity for central histamine H1 receptors, and H1 antagonism reduces histaminergic arousal, producing drowsiness and sedation. Human PET evidence shows high H1-receptor occupancy after quetiapine and a correlation between occupancy and subjective sleepiness. The early onset is also characteristic: the UK SmPC reports that somnolence in bipolar depression commonly begins within the first three days. Alpha-1 antagonism more typically causes postural hypotension and dizziness. Muscarinic antagonism causes effects such as dry mouth, constipation and blurred vision. D2 antagonism contributes to antipsychotic effects and extrapyramidal adverse effects, while 5-HT2A antagonism contributes to quetiapine's atypical antipsychotic profile but is not the principal explanation for marked sedation.

Reference: Sato H et al. Histamine H1 receptor occupancy by the new-generation antipsychotics olanzapine and quetiapine: a positron emission tomography study in healthy volunteers. Psychopharmacology. 2015;232:3497–3505. https://pubmed.ncbi.nlm.nih.gov/26146015/