Amitriptyline × duloxetine

Duloxetine moderately blocks CYP2D6 (an amitriptyline metabolic route); amitriptyline plasma levels rise. Both drugs are also serotonergic and noradrenergic – serotonin syndrome and cardiotoxicity risk.

Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia. Autonomic features: sweating, tachycardia, hypertension, fever. First signs appear within hours of co-administration.

Avoid the combination. For neuropathic pain, choose one: duloxetine (better profile in diabetic neuropathy) or gabapentin/pregabalin. Alternative for anxious depression: mirtazapine.