Amitriptyline × Warfarin

Amitriptyline is metabolised via CYP2C9 (a minor route) – weak competition with warfarin is possible. Mild INR rises have been reported when adding a TCA.

Mostly no changes. In some patients: a 10–15% INR rise 2–4 weeks after starting amitriptyline.

After starting amitriptyline, check INR at 2 and 4 weeks, then resume routine monitoring. If INR rises above target, reduce warfarin by 5–10%. Alternative antidepressants without CYP2C9 dependence: sertraline or agomelatine.