A 70-year-old widowed man presents with depression, marked weight loss, and severe insomnia. A single nightly dose of mirtazapine 15 mg improves sleep, appetite and mood. The pharmacological basis for choosing a low rather than higher dose in his case is:

• A Low doses act purely as alpha-2 antagonists, whereas high doses add dopamine blockade
• B Low doses selectively inhibit 5-HT2 and 5-HT3 receptors while sparing noradrenergic transmission
• C Low doses block H1 histamine receptors more completely, maximising sedation and appetite gain ✓
• D Low doses inhibit monoamine oxidase reversibly, avoiding the cheese reaction

Explanation

Mirtazapine blocks alpha-2 autoreceptors, enhancing noradrenergic and serotonergic release, and strongly blocks H1 and 5-HT2/5-HT3 receptors. At lower doses, H1 blockade dominates clinically, producing pronounced sedation and increased appetite, which suits this patient. As the dose increases, the activating noradrenergic effect becomes relatively more prominent and sedation often lessens, an unusual inverse dose-sedation relationship. Mirtazapine has no MAO inhibitory activity.

Reference: Katzung's Basic and Clinical Pharmacology, 15th ed.

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