Bupropion Does Not Effectively Reduce Alcohol Cravings and Should Not Be Used for This Purpose
Bupropion is not indicated for reducing alcohol cravings, and the limited clinical evidence in humans shows it does not improve alcohol-related outcomes when used as monotherapy. While preclinical animal studies suggest potential mechanisms for reducing binge-like alcohol consumption, these findings have not translated to meaningful clinical benefit in patients with alcohol use disorder 1, 2.
Evidence from Clinical Trials
The most relevant human data comes from a double-blind, placebo-controlled study in alcoholics undergoing treatment for alcohol use disorder 1. In this trial:
- Bupropion added to nicotine patch did not improve smoking cessation outcomes in alcoholics 1
- One-third of participants discontinued bupropion during the first 4 weeks due to tolerability issues 1
- The study focused on smoking cessation rather than alcohol cravings specifically, and found no advantage for bupropion 1
- Importantly, alcohol outcomes improved only in those who successfully quit smoking, not from bupropion treatment itself 1
A small pilot study (n=11) in early alcohol recovery showed bupropion reduced cigarette cravings but made no claims about alcohol cravings, and all participants remained abstinent from alcohol regardless of whether they received bupropion or placebo 3.
Preclinical Data Does Not Support Clinical Use
Animal studies show bupropion can reduce binge-like ethanol intake in mice, particularly when combined with naltrexone 2, 4. However:
- These are mouse models that do not reliably predict human clinical outcomes 2, 4
- The combination of varenicline and bupropion blocked the alcohol deprivation effect in rats, but this has not been tested in humans 4
- Translating rodent binge-drinking models to human alcohol use disorder has historically poor success rates 2
Critical Safety Concern: Alcohol Lowers Seizure Threshold
Alcohol consumption significantly increases the risk of bupropion-induced seizures 5. In mice, alcohol pretreatment lowered the seizure threshold for bupropion from a CD50 of 116.72 mg/kg to 89.40 mg/kg—a 23% reduction 5. This creates a dangerous situation:
- Patients with alcohol use disorder may continue drinking while taking bupropion 5
- Abrupt discontinuation of alcohol in patients on bupropion is an absolute contraindication due to dramatically increased seizure risk 6
- The baseline seizure risk with bupropion at therapeutic doses is already 0.1% (1 in 1,000), which increases substantially with alcohol exposure 7, 8, 5
What Bupropion IS Effective For
Bupropion has proven efficacy for:
- Smoking cessation: Achieves abstinence rates 9-10 percentage points above placebo when combined with behavioral support 7, 6, 8
- Major depressive disorder: Comparable efficacy to SSRIs with lower rates of sexual dysfunction 6, 8
- Comorbid depression and smoking in alcoholics: May address both conditions simultaneously, though evidence is limited 8, 3
Recommended Approach for Alcohol Cravings
For reducing alcohol cravings, use FDA-approved medications with proven efficacy:
- Naltrexone (oral or extended-release injectable) for reducing heavy drinking days and cravings
- Acamprosate for maintaining abstinence and reducing cravings
- Disulfiram for motivated patients seeking aversive therapy
- Topiramate (off-label) has emerging evidence for reducing heavy drinking
Do not prescribe bupropion with the expectation of reducing alcohol cravings—the evidence does not support this indication, and the safety risks in actively drinking patients are substantial 1, 5.