MajorTricyclic antidepressants (TCA)×SNRI (serotonin-norepinephrine reuptake inhibitor)
Updated · Methodology
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.
Summary of a multi-drug list →
Medicine list: everything you take in one place →
Sources
- FDA: Effexor XR (venlafaxine) prescribing information (2017)– ; DailyMed setid c848a5d8-ba94-4c84-80e3-0bf35fb8e32e
- AEMPS: Ficha técnica: Amitriptilina (nº registro 89862), sección 4.5 (2026)– AEMPS, CIMA, nº registro 89862, revisión 05/2026, sección 4.5