Can Contrave (bupropion and naltrexone) be used for smoking cessation?

Contrave for Smoking Cessation

Contrave (bupropion and naltrexone combination) is not FDA-approved for smoking cessation, though bupropion alone is an effective first-line pharmacotherapy for smoking cessation. 1

Recommended Pharmacotherapy for Smoking Cessation

First-Line Options

1. Combination Nicotine Replacement Therapy (NRT)

   • Considered a preferred primary therapy 1
   • Combines different forms of NRT (patch, gum, lozenge, etc.)
   • High-quality evidence supports efficacy 1

2. Varenicline

   • Considered a preferred primary therapy 1
   • More effective than bupropion alone in maintaining abstinence 2, 3
   • Partial agonist/antagonist for α4β2 nicotinic acetylcholine receptors 3

3. Bupropion SR (alone)

   • FDA-approved for smoking cessation 1, 4
   • Effective but considered subsequent to combination NRT or varenicline 1
   • Standard dose is 300 mg per day 1
   • Contraindicated in patients with brain metastases due to seizure risk 1

Treatment Algorithm

1. Initial treatment: Try either combination NRT or varenicline first 1
2. For persistent smoking or relapse: Switch to the other preferred option (if started with combination NRT, switch to varenicline, or vice versa) 1
3. Subsequent options: Consider combination NRT with bupropion or bupropion alone (category 2B recommendation) 1

Bupropion Component of Contrave

While Contrave contains bupropion (which is effective for smoking cessation), important considerations include:

• The bupropion SR dose in Contrave (360 mg daily at maintenance dose) 5 is similar to the standard dose used for smoking cessation (300 mg daily) 1
• Bupropion works as a norepinephrine and dopamine reuptake inhibitor 2
• It reduces craving and withdrawal symptoms, though less effectively than varenicline 2, 3

Naltrexone Component of Contrave

• Naltrexone is not FDA-approved for smoking cessation 1, 4
• Naltrexone is an opioid antagonist primarily used for alcohol and opioid dependence 5
• No established evidence supports naltrexone alone for smoking cessation in clinical guidelines 1

Research on Naltrexone-Bupropion Combination for Smoking

Limited research exists on the combination specifically for smoking cessation:

• One small open-label study (n=30) of naltrexone/bupropion combination in overweight/obese smokers showed promising results with 48% continuous abstinence rate at weeks 4-12 6
• This combination was associated with decreased nicotine use, limited withdrawal symptoms, and no significant weight gain 6
• However, this limited evidence is insufficient to recommend over established first-line therapies

Important Considerations

• Contraindications: Bupropion should be avoided in patients with seizure disorders or brain metastases 1, 5
• Side effects: Common side effects include nausea, insomnia, headache, constipation, and dry mouth 5, 3
• Drug interactions: Contrave is contraindicated with MAOIs and may have reduced efficacy with opioids 5
• Follow-up: Initial follow-up within 2 weeks of starting therapy is important to assess efficacy and toxicity 1

Conclusion

While bupropion alone is an established smoking cessation aid, the combination product Contrave (bupropion-naltrexone) is not FDA-approved for smoking cessation and lacks sufficient evidence to recommend over established first-line therapies. Clinicians should use evidence-based approaches like combination NRT or varenicline as first-line options, with bupropion alone as a subsequent option.