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Clomipramine Serotonergic — MRCPsych Paper B MCQ

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ModerateAnxiety & Stress-Related DisordersClomipramine SerotonergicMRCPsych Paper B

Which pharmacological property best explains why clomipramine, unlike most other tricyclic antidepressants, has established efficacy in obsessive-compulsive disorder?

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Correct answer: EParticularly potent inhibition of serotonin reuptake

Clomipramine is a tricyclic antidepressant, but its particularly potent inhibition of serotonin reuptake distinguishes it pharmacologically from predominantly noradrenergic TCAs and is associated with its anti-obsessional efficacy. Its SmPC states that clomipramine inhibits both serotonin and noradrenaline reuptake, with serotonin reuptake inhibition being the more important activity. NICE correspondingly treats clomipramine as the exception among TCAs for OCD, although SSRIs are generally preferred initially because of their safer adverse-effect profile. Predominant noradrenaline reuptake inhibition is therefore incorrect. Clomipramine is not a 5-HT1A partial agonist, a monoamine oxidase inhibitor or a dopamine D2 antagonist; those mechanisms describe other psychotropic drug classes rather than its principal therapeutic action.

Reference: Viatris. Clomipramine 10 mg Capsules, Hard: Summary of Product Characteristics, section 5.1 Pharmacodynamic properties. Text revised July 2026. https://www.medicines.org.uk/emc/product/2552/smpc