Amitriptyline Interactions

St. John's wort induces CYP3A4 and CYP2D6 enzymes that metabolize amitriptyline, reducing its plasma concentrations by up to 22%, while simultaneously adding serotonergic activity that can trigger serotonin syndrome. The combined result is paradoxical: less antidepressant effect plus higher risk of a potentially fatal serotonin reaction.

Amitriptyline is a tricyclic antidepressant with strong sedating, anticholinergic, and antihistaminic effects. Combining it with alcohol — also a CNS depressant — produces marked additive sedation, impaired psychomotor performance, and increased risk of falls, accidents, and respiratory depression in overdose.