Major
Amitriptyline × Tramadol
Tricyclic antidepressants (TCA)×Other opioids
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.