Which antidepressant mechanism uniquely explains the therapeutic action of mirtazapine and differentiates it from SSRIs and SNRIs?

• A Selective serotonin reuptake inhibition with 5-HT2A antagonism
• B Noradrenergic and specific serotonergic antidepressant (NaSSA): alpha-2 presynaptic antagonism plus 5-HT2A and 5-HT3 blockade ✓
• C Monoamine oxidase inhibition with irreversible binding to MAO-A
• D Dual serotonin-norepinephrine reuptake inhibition with melatonin receptor agonism

Explanation

Mirtazapine is a NaSSA (Noradrenergic and Specific Serotonergic Antidepressant). It blocks presynaptic alpha-2 autoreceptors and alpha-2 heteroreceptors, increasing both norepinephrine and serotonin release. Simultaneously, it blocks postsynaptic 5-HT2A receptors (reducing sexual dysfunction and anxiety) and 5-HT3 receptors (reducing nausea). H1 antihistamine blockade causes sedation and weight gain (useful in anorexia/insomnia). It does not inhibit reuptake transporters. Agomelatine combines melatonin agonism with 5-HT2C antagonism. Phenelzine inhibits MAO-A irreversibly. The combination of increased NE/5-HT with serotonin receptor selectivity is its unique pharmacological signature.

Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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