Major
Tramadol × venlafaxine
Other opioids×SNRI (serotonin-norepinephrine reuptake inhibitor)
Mechanism
Venlafaxine (SNRI) + tramadol – serotonin syndrome plus additive seizure risk. Tramadol itself is a weak serotonin-norepinephrine reuptake inhibitor with proconvulsant effect.
Symptoms
Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia. Autonomic features: sweating, tachycardia, fever.
Management
Avoid the combination. For analgesia on venlafaxine, use paracetamol, an NSAID, or morphine/oxycodone (without serotonergic activity). 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.