A 32-year-old man with generalized anxiety disorder and MDD is started on an antidepressant that simultaneously blocks norepinephrine and serotonin reuptake transporters. After 3 weeks, he reports improved sleep and anxiety. Which drug is this, and what is its mechanism that explains improved sleep?
- A Venlafaxine; SNRI with antihistaminergic sedation
- B Duloxetine; SNRI with anticholinergic sedation
- C Bupropion; NDRI with sedative effects from NET blockade
- D Mirtazapine; NaSSA with alpha-2 blockade and H1 antihistaminergic sedation ✓
Explanation
Mirtazapine (a Noradrenergic and Specific Serotonergic Antidepressant, NaSSA) works by blocking presynaptic alpha-2 autoreceptors and heteroreceptors (increasing norepinephrine and serotonin release) and by blocking postsynaptic 5-HT2A, 5-HT2C, and 5-HT3 receptors (which reduces anxiety and nausea). Critically, mirtazapine potently blocks H1 histamine receptors, which accounts for its pronounced sedation and weight gain—clinically useful for depression with insomnia and poor appetite. Venlafaxine and duloxetine are SNRIs without significant antihistaminergic activity. Bupropion is stimulating (blocks DAT and NET) and not used for sleep.
Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.
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