mirtazapine

Mirtazapine is an antidepressant in the class often described as noradrenergic and specific serotonergic antidepressant (NaSSA). It is approved for the treatment of major depressive disorder and is sometimes used off-label to address sleep disturbances or loss of appetite associated with depression.

The drug has a distinctive pharmacology. It blocks central presynaptic alpha-2 adrenergic receptors, increasing release of norepinephrine and serotonin. It also antagonizes several serotonin receptors (notably 5-HT2 and 5-HT3) and the H1 histamine receptor. The net effect is mood improvement with sedative and orexigenic properties, which can be advantageous in depressed patients with insomnia or weight loss.

Mirtazapine is taken orally, available in standard tablet and orally disintegrating tablet forms. Peak plasma concentrations occur within a few hours, and the elimination half-life is approximately 20 to 40 hours, supporting once-daily dosing. It is metabolized in the liver primarily by cytochrome P450 enzymes and excreted in urine and feces.

Typical dosing starts at 15 mg taken at bedtime, with gradual increases of 15 mg every one to two weeks as needed, up to a usual maximum of 45 mg daily. The bedtime dosing leverages its sedative effects and can help with adherence. Some patients may experience antidepressant benefits within one to two weeks, though full effects often take several weeks.

Common adverse effects include drowsiness, weight gain, increased appetite, dry mouth, constipation, and dizziness. Less common but notable risks include metabolic changes, neutropenia, or hepatotoxicity. Caution is advised with alcohol and other central nervous system depressants, and concomitant use with monoamine oxidase inhibitors is contraindicated. Pregnancy and breastfeeding should be discussed with a clinician, weighing potential benefits and risks.