Can Wellbutrin (bupropion) and Naltrexone be used to treat alcohol abuse?

Bupropion and Naltrexone for Alcohol Abuse Treatment

The combination of bupropion (Wellbutrin) and naltrexone is an effective treatment option for alcohol abuse, particularly for patients who experience alcohol cravings and have comorbid depression or are attempting smoking cessation. This combination therapy works through complementary mechanisms that target both the reward pathways and craving aspects of alcohol use disorder.

Mechanism and Efficacy

• Naltrexone: An opioid antagonist that blocks the rewarding effects of alcohol by antagonizing opioid receptors 1
• Bupropion: A dopamine and norepinephrine reuptake inhibitor that modulates the central reward pathways triggered by alcohol 1

The combination works synergistically - naltrexone antagonizes an inhibitory feedback loop that would otherwise limit bupropion's anorectic properties, and together they have been shown to be more effective than either medication alone 2, 3.

Evidence Supporting Combination Therapy

Research demonstrates that combining these medications can be particularly effective:

• In animal studies, the combination of naltrexone and bupropion reduced alcohol consumption more effectively than either drug alone, even when using lower doses of each medication 2
• A preliminary human study showed that combined naltrexone and bupropion therapy reduced both the number of drinks per binge drinking day (from 7.8 to 6.4) and the percentage of binge drinking days per month (from 19% to 5%) 3

Patient Selection

This combination therapy is particularly beneficial for:

1. Patients with comorbid depression: The bupropion component can assist in treating depression while addressing alcohol use 4
2. Patients attempting smoking cessation: Bupropion is FDA-approved for smoking cessation, making this combination ideal for patients with both alcohol use disorder and tobacco dependence 4
3. Patients with alcohol cravings: The combination targets craving mechanisms more effectively than monotherapy 1
4. "Reward drinkers": Patients whose drinking is driven by positive reinforcement (reward seeking) respond particularly well to naltrexone, with up to 83% reduction in heavy drinking episodes 5

Dosing and Administration

• Standard dosing: Naltrexone 50 mg daily with bupropion SR 300-360 mg daily (divided doses) 4, 3
• Titration: Start with lower doses and gradually increase over 4 weeks to minimize side effects, particularly nausea 4
• Duration: Treatment should be continued long-term for maintenance of abstinence

Contraindications and Precautions

• Absolute contraindications:

  • Concurrent opioid use (naltrexone will precipitate withdrawal) 4
  • Seizure disorders (bupropion lowers seizure threshold) 4
  • Uncontrolled hypertension 4
  • Use of MAOIs within 14 days 4
  • Pregnancy 4

• Relative contraindications/Use with caution:

  • Hepatic impairment (both medications undergo hepatic metabolism) 1
  • History of seizures or conditions that lower seizure threshold 1
  • Planned surgical procedures requiring opioid analgesia (discontinue naltrexone before procedure) 1

Monitoring

1. Before initiation:

   • Assess baseline liver function
   • Screen for current opioid use
   • Check blood pressure and cardiovascular risk factors
   • Evaluate psychiatric status

2. During treatment:

   • Monitor blood pressure regularly, especially during the first 8 weeks 4
   • Assess liver function periodically
   • Evaluate for neuropsychiatric adverse effects, particularly in younger patients 1
   • Monitor for efficacy (reduction in drinking days/amounts)

3. Discontinuation consideration:

   • If less than 5% weight loss after 12 weeks at maintenance dose (indicating poor response) 4
   • Development of significant side effects
   • Return to heavy drinking despite adherence to medication

Side Effects

Common side effects include:

• Nausea (most common, affecting up to 30% of patients) 4
• Constipation
• Headache
• Dizziness
• Insomnia
• Dry mouth 4

Alternative Pharmacotherapies for Alcohol Use Disorder

If bupropion/naltrexone is contraindicated or poorly tolerated, consider:

• Acamprosate: Safe in hepatic impairment, works through NMDA receptor antagonism 1
• Baclofen: GABA-B receptor agonist with evidence of benefit in patients with cirrhosis 1
• Gabapentin: Modulates GABA activity, useful in patients with renal impairment 1

Clinical Pearls

• Approximately 25% of patients discontinue the combination due to adverse effects 4
• Patients with diabetes may experience modest improvements in glycemic control with this combination 4
• The combination may be more effective at lower doses than higher doses of either medication alone, potentially reducing side effects 2
• Discontinue naltrexone before procedures requiring opioid analgesia 1
• Patients should be counseled about the risk of hepatotoxicity with naltrexone 1

By targeting multiple neurobiological pathways involved in alcohol use disorder, the combination of bupropion and naltrexone offers a promising approach for patients struggling with alcohol abuse, particularly those with specific comorbidities like depression or tobacco use.