Linezolid × Mirtazapine

Mirtazapine increases serotonin release by blocking presynaptic α2-adrenergic autoreceptors. Linezolid reversibly inhibits MAO. Combined action multiplies serotonergic activity.

Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia, dilated pupils. Autonomic features: profuse sweating, tachycardia, hypertension, fever above 38.5 °C. Severe cases progress to seizures, rhabdomyolysis, disseminated intravascular coagulation, and death. First signs appear within hours of concurrent dosing.

The combination is not used: the FDA label for mirtazapine contraindicates it with MAO inhibitors, including linezolid, and within 14 days of stopping them. A planned linezolid course starts about 2 weeks after the last mirtazapine dose, the interval given in the mirtazapine SmPC. If linezolid is needed urgently, mirtazapine is stopped before the first antibiotic dose and the patient is watched for serotonin syndrome throughout the course. Mirtazapine is restarted no earlier than 14 days after the last linezolid dose. Trazodone is not a bridge: its FDA label also contraindicates linezolid. For gram-positive infections vancomycin or daptomycin are chosen, as they do not inhibit MAO.