Does the combination of Bupropion (Wellbutrin), Naltrexone, and Topiramate (Topamax) aid in weight loss?

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Last updated: May 29, 2025View editorial policy

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From the Guidelines

The combination of Wellbutrin (bupropion), naltrexone, and Topamax (topiramate) may help with weight loss, though this specific three-medication combination is not FDA-approved for this purpose, and the most recent evidence suggests using naltrexone-bupropion ER with lifestyle interventions as the preferred approach 1.

Key Considerations

  • Wellbutrin and naltrexone are combined in the FDA-approved weight loss medication Contrave, while Topamax is sometimes prescribed off-label for weight management.
  • The AGA suggests using naltrexone-bupropion ER with lifestyle interventions, compared with lifestyle interventions alone, based on a conditional recommendation with moderate certainty 1.
  • The guideline panel deemed moderate magnitude of benefit in weight loss, whereas the magnitude of undesirable effects was judged to be small, favoring the use of naltrexone-bupropion ER 1.

Medication Details

  • Typical dosing for weight loss would be Contrave (naltrexone 8-32mg/bupropion 90-360mg daily) plus Topamax (25-100mg daily), gradually increased to minimize side effects.
  • Potential side effects include nausea, headache, insomnia, dry mouth, dizziness, and mood changes.

Important Warnings

  • This combination should only be used under medical supervision as it carries risks including seizures, suicidal thoughts, and birth defects.
  • Medical monitoring is essential, especially for those with kidney problems, seizure disorders, or mental health conditions.

Lifestyle Interventions

  • The combination works best when combined with diet and exercise, and results vary significantly between individuals 1.

From the Research

Combination Therapy for Weight Loss

The combination of wellbutrin (bupropion), naltrexone, and topamax (topiramate) for weight loss is not directly addressed in the provided studies. However, the individual components and similar combinations are discussed:

  • Bupropion and naltrexone combination: Studies have shown that this combination is effective for weight loss 2, 3.
  • Topiramate combination: Phentermine and topiramate extended release combination has been evaluated in clinical studies and approved by the FDA for chronic weight management 4, 5.
  • Naltrexone and bupropion: This combination has been shown to be effective in weight loss, with significant improvements in weight and body mass index (BMI) 2, 3.

Efficacy and Safety

The efficacy and safety of combination therapies for weight loss have been assessed in several studies:

  • A systematic review of naltrexone or naltrexone/bupropion for weight loss found that the combination was effective and well-tolerated 2.
  • A review of combination therapies for obesity discussed the safety concerns and potential benefits of combining medications like bupropion, naltrexone, and topiramate 5.
  • A meta-regression analysis of randomized controlled trials found that bupropion alone and in combination with naltrexone resulted in significant weight loss and improvements in BMI and waist circumference 3.

Potential Benefits and Limitations

While the combination of wellbutrin, naltrexone, and topamax may be promising for weight loss, it is essential to consider the potential benefits and limitations:

  • Combination therapies may offer improved efficacy and reduced side effects compared to monotherapies 6.
  • However, the safety and efficacy of this specific combination have not been directly assessed in the provided studies.
  • Further research is needed to determine the optimal combination and dosage of these medications for weight loss 4, 6, 5, 3.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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