Is Wellbutrin Safe with Alcohol?
Wellbutrin (bupropion) and alcohol should not be combined—the FDA explicitly states that alcohol consumption during bupropion treatment should be minimized or avoided due to rare reports of adverse neuropsychiatric events, reduced alcohol tolerance, and critically, a significantly lowered seizure threshold. 1
Critical Safety Concerns
Seizure Risk - The Primary Danger
Alcohol dramatically lowers the seizure threshold when combined with bupropion. In animal studies, the convulsive dose required to induce seizures in 50% of subjects (CD50) dropped from 116.72 mg/kg for bupropion alone to 89.40 mg/kg when combined with alcohol—a 23% reduction in seizure threshold. 2
The percentage of seizures increased substantially with alcohol pretreatment: at the 100 mg/kg dose, seizures occurred in 20% with bupropion alone versus 70% when combined with alcohol. 2
Abrupt discontinuation of alcohol in patients with alcohol dependence is an absolute contraindication for bupropion use due to the dramatically increased seizure risk during alcohol withdrawal. 3
Neuropsychiatric Adverse Events
The FDA has documented rare but serious reports of adverse neuropsychiatric events in patients drinking alcohol while on bupropion, including reduced alcohol tolerance. 1
A case report documented unexpected aggressive behavior and violence in a previously non-violent social drinker after consuming alcohol while taking bupropion 150 mg/day (just 3 days into treatment), which was attributed to the bupropion-alcohol interaction by multiple expert witnesses. 4
Pharmacokinetic Considerations
While earlier studies showed no pharmacokinetic interaction between bupropion and alcohol (blood levels of each drug remain unchanged), this does not mean the combination is safe—the pharmacodynamic interaction (seizure threshold lowering and neuropsychiatric effects) is the critical concern. 5, 6
The lack of kinetic interaction means dose adjustments won't mitigate the risks; the issue is the combined effect on the central nervous system. 5
Clinical Context: Alcohol Use Disorder
For patients with alcohol dependence who are in early recovery and abstinent from alcohol, bupropion can be safely used for smoking cessation. A pilot study showed bupropion was effective for smoking cessation in alcohol-dependent patients who remained abstinent from alcohol throughout treatment, with no serious adverse events. 7
The key distinction: bupropion is safe in patients who are abstinent from alcohol, but dangerous when alcohol is actively consumed. 7
Practical Recommendations
Screen all patients starting bupropion about their alcohol consumption patterns. Patients who regularly consume alcohol or binge drink should be counseled that this is a contraindication to safe bupropion use. 1
If a patient on bupropion reports any alcohol consumption, strongly advise complete alcohol avoidance and monitor closely for neuropsychiatric symptoms and any signs of seizure activity. 1
For patients with alcohol use disorder, bupropion should only be initiated after achieving stable abstinence, and never during active drinking or the acute withdrawal phase. 3, 7
Patients should be explicitly warned that even moderate social drinking poses significant risks when combined with bupropion, as demonstrated by the case of aggressive behavior after sharing just one bottle of wine at dinner. 4