Major
Probable
Description
Bupropion combined with tramadol increases the risk of both serotonin syndrome and seizures, representing a serious dual-hazard drug combination.
Mechanism
Bupropion inhibits dopamine and norepinephrine reuptake and is a CYP2D6 inhibitor that elevates tramadol's serotonergic M1 metabolite; the combination raises CNS serotonin and lowers the seizure threshold.
Clinical Significance
Both serotonin syndrome and seizure events have been documented in case reports with this combination.
Management
Avoid concurrent use; if necessary, use the lowest effective tramadol dose and monitor for neurological symptoms closely.