A 38-year-old man with major depressive disorder has had a partial response to an adequate trial of sertraline 200 mg daily. Following specialist

Question

A 38-year-old man with major depressive disorder has had a partial response to an adequate trial of sertraline 200 mg daily. Following specialist review, adding mirtazapine is considered. Which statement most accurately describes the pharmacological rationale for this combination and its place in current UK practice?

Accepted Answer

Sertraline inhibits serotonin reuptake, whereas mirtazapine antagonises presynaptic alpha-2 and 5-HT2/3 receptors, providing complementary monoaminergic effects; specialist use may be considered despite an increased side-effect burden.

Answer

The combination is contraindicated because using two serotonergic antidepressants predictably causes serotonin syndrome despite their distinct receptor actions.

Answer

Both drugs primarily inhibit the serotonin transporter; combining them increases transporter occupancy beyond that achievable with sertraline monotherapy.

Answer

Sertraline inhibits serotonin reuptake, whereas mirtazapine blocks postsynaptic 5-HT1 receptors, reducing serotonergic transmission while reliably improving antidepressant efficacy.

Answer

Mirtazapine antagonises alpha-2 receptors to suppress noradrenaline and serotonin release, so it is added principally to counter sertraline-induced activation.

SSRI-Mirtazapine Combination Rationale — MRCPsych Paper B MCQ