Major
Bupropion × Tramadol
Other antidepressants (NDRI)×Other opioids
Mechanism
Bupropion blocks CYP2D6 – the route converting tramadol to its active M1 metabolite. Analgesia falls but parent tramadol accumulates, raising seizure risk. Both drugs also lower the seizure threshold.
Symptoms
Seizures (generalised tonic-clonic or focal), agitation, tremor, insomnia. Patients with prior epilepsy or eating disorders are at particular risk.
Management
Avoid the combination. For analgesia on bupropion, use paracetamol, an NSAID, or morphine/oxycodone. For neuropathic pain, gabapentin or pregabalin.
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.