The unique antidepressant effect of mirtazapine compared to SSRIs is mediated through:

• A Inhibition of serotonin and noradrenaline reuptake transporters
• B MAO-A inhibition increasing 5HT and NA levels
• C Blockade of presynaptic α2-autoreceptors and α2-heteroreceptors, increasing NA and 5HT release; plus 5HT2 and 5HT3 antagonism ✓
• D Selective D2 partial agonism in the prefrontal cortex

Explanation

Mirtazapine is a noradrenergic and specific serotonergic antidepressant (NaSSA). It blocks presynaptic α2-autoreceptors on noradrenergic neurons (disinhibiting NA release) and α2-heteroreceptors on serotonergic neurons (disinhibiting 5HT release), thus increasing both neurotransmitters. Simultaneously, 5HT2 (avoiding sexual dysfunction, anxiety) and 5HT3 (preventing nausea/vomiting) receptor antagonism ensures that the enhanced 5HT acts selectively via 5HT1A receptors. Its strong H1 antihistamine action causes sedation and increased appetite.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.