Amitriptyline × Linezolid

Amitriptyline, a tricyclic antidepressant, blocks serotonin and norepinephrine reuptake. Linezolid reversibly inhibits MAO. Combined action sharply raises synaptic monoamines, risking serotonin syndrome and hypertensive crisis.

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 prescribed. Stop amitriptyline 1–2 weeks before linezolid. If linezolid is urgently needed, switch the patient to mianserin or agomelatine, which lack a strong serotonergic profile. Alternative antibiotics: vancomycin, daptomycin.