Which antidepressant mechanism is unique to mirtazapine compared to SSRIs and SNRIs, and which specific side effects result from this unique mechanism?

• A Reuptake inhibition of dopamine; side effects are hypertension and tachycardia
• B Selective norepinephrine reuptake inhibition; side effects are urinary retention and dry mouth
• C Presynaptic alpha-2 autoreceptor and heteroreceptor antagonism (increasing NE and 5-HT release) combined with 5-HT2 and 5-HT3 receptor blockade and H1 antihistaminism; side effects are weight gain, sedation, and increased appetite ✓
• D MAO-B inhibition; side effects are hypertensive crisis with tyramine

Explanation

Mirtazapine is a noradrenergic and specific serotonergic antidepressant (NaSSA). Its unique mechanism involves presynaptic alpha-2 adrenoceptor antagonism (auto- and heteroreceptors), which disinhibits NE and 5-HT release. Additionally, it blocks 5-HT2A (anxiolytic, pro-sleep), 5-HT2C (weight gain, increased appetite), 5-HT3 (antiemetic), and H1 (sedation, weight gain) receptors. Consequently, sedation and weight gain are predictable and clinically useful adverse effects (useful in depressed patients with insomnia and anorexia), while nausea and sexual dysfunction common with SSRIs are minimal. Agranulocytosis is a rare but serious adverse effect requiring monitoring.

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

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Written and medically reviewed by the StethoPrep medical team.