MAJOR — Use With Caution
FDA-documented dual risk: CYP2D6 inhibition (pharmacokinetic) plus additive seizure threshold lowering (pharmacodynamic). Avoid if possible.
Evidence level: STRONG
Wellbutrin (bupropion) and tramadol are a risky combination because both medications lower your seizure threshold, and Wellbutrin also causes tramadol to build up in your blood. The combined seizure risk is significant.
Dual mechanism: bupropion inhibits CYP2D6 (increasing tramadol levels) AND both lower seizure threshold. FDA bupropion label warns about seizure risk with drugs that lower seizure threshold. Tramadol FDA label warns about seizure risk.
Tell your doctor about both medications. The seizure risk is real and increases with higher doses of either drug. Alternative pain medications or antidepressants should be considered.
Take Tramadol exactly as prescribed — set alarms for scheduled doses. Bupropion follows its normal schedule. Opioids slow GI transit, which can affect absorption of other medications. Take with food if nausea occurs. Never combine with alcohol.
Higher risk for: elderly, opioid-naive patients, those with sleep apnea, respiratory conditions, concurrent CNS depressants (benzodiazepines, alcohol), liver impairment, or history of substance use disorder.
Seizures (can occur without warning), confusion, agitation, muscle twitching, tremor
Consider alternative pain medication (non-seizure-risk) or alternative antidepressant. If combination is necessary, use lowest effective doses. Contraindicated in patients with seizure history.
Opioid combinations carry serious risks including respiratory depression. Talk to your pain management specialist about non-opioid alternatives: physical therapy, NSAIDs (if appropriate), nerve blocks, or non-sedating supplements like PEA (palmitoylethanolamide) or curcumin for inflammation.
Wellbutrin (bupropion) and tramadol are a risky combination because both medications lower your seizure threshold, and Wellbutrin also causes tramadol to build up in your blood. The combined seizure risk is significant.
Take Tramadol exactly as prescribed — set alarms for scheduled doses. Bupropion follows its normal schedule. Opioids slow GI transit, which can affect absorption of other medications. Take with food if nausea occurs. Never combine with alcohol.
Seizures (can occur without warning), confusion, agitation, muscle twitching, tremor
Opioid combinations carry serious risks including respiratory depression. Talk to your pain management specialist about non-opioid alternatives: physical therapy, NSAIDs (if appropriate), nerve blocks, or non-sedating supplements like PEA (palmitoylethanolamide) or curcumin for inflammation.
Consider alternative pain medication (non-seizure-risk) or alternative antidepressant. If combination is necessary, use lowest effective doses. Contraindicated in patients with seizure history.
Or browse the full interaction database (121,000+ pairs).