Major
Amitriptyline × venlafaxine
Tricyclic antidepressants (TCA)×SNRI (serotonin-norepinephrine reuptake inhibitor)
Mechanism
Venlafaxine (SNRI) has serotonin and noradrenergic activity; amitriptyline (TCA) acts the same way. Co-administration: additive serotonin syndrome, hypertension, and cardiotoxicity risk.
Symptoms
Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia. Autonomic features: sweating, tachycardia, hypertension, fever. First signs appear within hours of co-administration.
Management
Avoid the combination. For neuropathic pain, choose one: venlafaxine (SNRI) or gabapentin/pregabalin. Alternative for depression: mirtazapine or agomelatine.
Check the full regimen, not just this pair
Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.