From the Guidelines
The combination of phentermine, topiramate, bupropion, and naltrexone is not recommended for weight loss due to potential drug interactions and overlapping side effects, and instead, either Qsymia (phentermine/topiramate) or Contrave (bupropion/naltrexone) should be used as FDA-approved combination medications. The AGA clinical practice guideline on pharmacological interventions for adults with obesity suggests the use of semaglutide 2.4 mg, liraglutide 3.0 mg, phentermine-topiramate ER, and naltrexone-bupropion ER for long-term management of overweight and obesity, based on moderate certainty evidence 1.
When considering weight loss medications, it's essential to evaluate individual health factors, as these medications can cause side effects and are contraindicated in certain conditions. Qsymia and Contrave work through different mechanisms, with Qsymia combining an appetite suppressant with an anticonvulsant that reduces hunger, and Contrave affecting both reward pathways and hunger signals in the brain.
Key points to consider when using these medications include:
- Typical starting dose of Qsymia: 3.75 mg phentermine/23 mg topiramate once daily, potentially increasing to 15 mg/92 mg
- Typical starting dose of Contrave: one tablet daily containing 8 mg naltrexone/90 mg bupropion, potentially increasing to two tablets twice daily
- Potential side effects: increased heart rate, insomnia, dry mouth, constipation, and headaches
- Contraindications: uncontrolled hypertension, seizure disorders, or eating disorders
- Importance of lifestyle modifications, including diet and exercise, alongside medication use 1.
Ultimately, a healthcare provider should evaluate which option might be most appropriate based on individual health factors, considering the potential benefits and risks of each medication.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Combination Therapy for Obesity
The combination of phentermine, topiramate, bupropion, and naltrexone is a topic of interest in the treatment of obesity. According to 2, the FDA has approved several anti-obesity medications, including phentermine/topiramate and naltrexone/bupropion, for chronic weight management.
Efficacy of Combination Therapies
- The study 2 found that phentermine/topiramate resulted in a 6.8% weight reduction, while naltrexone/bupropion resulted in a 4.0% weight reduction.
- Another study 3 evaluated the efficacy of naltrexone/bupropion in patients with binge-eating disorder and obesity, and found that 45.5% of patients achieved a 3% weight loss.
- A review of anti-obesity drugs for the treatment of binge eating disorder 4 found that phentermine/topiramate, naltrexone/bupropion, and other anti-obesity drugs may achieve improvements in both body weight and severity and frequency of binge episodes.
Safety Assessment
- A safety assessment of combination therapies for obesity 5 discussed the safety concerns of naltrexone/bupropion and phentermine-topiramate, and emphasized the importance of safety assessment due to the high number of potential users on a chronic basis.
- The study 6 noted that combination therapy can optimize efficacy for weight management while minimizing adverse effects, and discussed the potential for new combination therapies, including the combination of phentermine with other medications.
Potential for Combination Therapies
- The study 6 suggested that combination therapy is a promising new area in obesity treatment, and that many other possibilities exist, including the combination of phentermine with a sodium glucose co-transporter 2 inhibitor.
- The review 4 noted that findings from ongoing clinical trials are likely to provide further insight into the possible role of anti-obesity drugs, including combination therapies, for treating binge eating disorder.