Bupropion is Contraindicated During Alcohol Withdrawal
Bupropion is absolutely contraindicated in patients undergoing alcohol withdrawal due to a significantly increased risk of seizures. 1 The FDA label explicitly lists "patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs" as contraindications for bupropion therapy.
Mechanism and Evidence
The contraindication is based on several key factors:
Seizure risk: Bupropion lowers the seizure threshold in a dose-dependent manner 1. This is particularly dangerous during alcohol withdrawal, which independently increases seizure risk.
Pharmacological interaction: Research demonstrates that alcohol significantly lowers the seizure threshold when co-administered with bupropion in animal models 2. The convulsive dose of bupropion required to induce seizures in 50% of mice (CD50) was reduced from 116.72 mg/kg to 89.40 mg/kg when combined with alcohol.
FDA labeling: The FDA drug label explicitly states that bupropion is "contraindicated in patients undergoing abrupt discontinuation of alcohol" 1.
Clinical Implications
During alcohol withdrawal:
- Patients are already at high risk for seizures, with withdrawal seizures typically peaking 3-5 days after cessation 3
- Benzodiazepines are the first-line treatment for alcohol withdrawal syndrome, not antidepressants 3
- The combination of alcohol withdrawal physiology and bupropion's seizure-lowering effect creates a dangerous synergy
Alternative Approaches
For patients requiring treatment for both depression and alcohol withdrawal:
Stabilize withdrawal first: Complete alcohol withdrawal management with benzodiazepines before initiating bupropion therapy
Consider safer alternatives: If antidepressant therapy is needed during withdrawal, consider options that don't lower seizure threshold
Wait period: Allow at least 7-14 days after completion of alcohol withdrawal before initiating bupropion
Important Considerations
Bupropion has been studied for alcohol use disorder treatment after withdrawal is complete, showing no negative effects on alcohol relapse compared to SSRIs 4
Bupropion is the third leading cause of drug-related seizures presenting to emergency departments (1.4% of new-onset seizures), even at therapeutic doses of 450 mg/day or less 5
Risk factors that further increase seizure risk with bupropion include sleep deprivation, history of attention deficit disorder, bulimia, and previous heavy alcohol use 5
In summary, while bupropion may be considered for patients with alcohol use disorder after they have safely completed withdrawal, it must never be initiated during the active withdrawal period due to the significantly elevated seizure risk.