MajorTricyclic antidepressants (TCA)×Other opioids
Updated · Methodology
Mechanism
Dual risk. Tramadol blocks serotonin and norepinephrine reuptake and lowers seizure threshold. Amitriptyline (TCA) also blocks both reuptakes and itself provokes seizures in overdose. Combined action – serotonin syndrome and seizure risk.
Symptoms
Serotonin syndrome (agitation, tremor, tachycardia, hyperthermia) plus seizure risk. QT prolongation – both drugs contribute. Older patients: ataxia and fall risk.
Management
Avoid the combination. For neuropathic pain on a TCA, choose gabapentin or pregabalin. For analgesia on amitriptyline, use paracetamol, an NSAID, or morphine/oxycodone.
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: Tramadol hydrochloride tablet (Amneal Pharmaceuticals NY LLC) – Prescribing Information (2017)– ; DailyMed setid 8ec4e4e5-a56e-4198-8428-6b770b9bf27d
- AEMPS: Ficha técnica: Amitriptilina (nº registro 89862), sección 4.5 (2026)– AEMPS, CIMA, nº registro 89862, revisión 05/2026, sección 4.5
- AEMPS: Ficha técnica: Tramadol (nº registro 63440), sección 4.5 (2024)– AEMPS, CIMA, nº registro 63440, revisión 09/2024, sección 4.5