From the Guidelines
The combination of Wellbutrin (bupropion) and naltrexone, not natroxelone, is recommended for weight loss, as evidenced by the FDA-approved medication Contrave, which has been shown to result in a 5.0% mean weight loss from baseline 1. The medication works by affecting both appetite and food cravings through different mechanisms in the brain, with bupropion affecting dopamine and norepinephrine pathways to reduce appetite, and naltrexone blocking opioid receptors to reduce food cravings and pleasure from eating. Key points to consider when prescribing this combination include:
- Typical starting dose: one tablet (naltrexone 8mg/bupropion 90mg) daily, gradually increasing over four weeks to the maintenance dose of two tablets twice daily
- Common side effects: nausea, constipation, headache, and insomnia
- Contraindications: uncontrolled high blood pressure, seizure disorders, eating disorders, or those taking certain medications including opioids
- Importance of using Contrave alongside a reduced-calorie diet and increased physical activity for best results
- Need for regular medical follow-up to monitor progress and manage any side effects, as highlighted in the 2023 standards of care in diabetes 1.
From the Research
Combination Therapy for Weight Loss
The combination of naltrexone and bupropion has been studied for its efficacy and safety in achieving weight loss.
- The combination of 32 mg naltrexone and 360 mg bupropion prolonged release was approved by the FDA and EMA as an adjunct to a comprehensive lifestyle intervention for weight loss 2.
- Randomized controlled trials have shown that naltrexone/bupropion combination therapy can result in significant weight loss, with a placebo-subtracted weight loss of 3.2-5.2% over 56 weeks 2, 3, 4.
- The combination therapy has also been shown to improve other health outcomes, such as decreasing waist circumference, serum triglycerides, and insulin resistance, and increasing high-density lipoprotein-cholesterol (HDL-C) 2, 4.
Safety and Tolerability
The safety and tolerability of the naltrexone/bupropion combination have been evaluated in several studies.
- Common side effects associated with the combination therapy include nausea, constipation, vomiting, dizziness, and dry mouth 2, 3, 4, 5.
- Serious adverse effects, such as suicidal thoughts and seizures, have been reported but are rare 2.
- The combination therapy has been shown to be well-tolerated in the majority of patients, with a low dropout rate due to adverse events 2, 5.
Efficacy in Special Populations
The efficacy of the naltrexone/bupropion combination in special populations, such as those with sleep apnea, osteoarthritis, or extreme BMIs, has not been extensively studied.
- However, the combination therapy has been shown to be effective in patients with diabetes, with a decrease in hemoglobin A1c (HbA1c) of approximately 0.5% more than placebo 4.
- Further studies are needed to determine the effect of the naltrexone/bupropion combination on cardiovascular outcomes and in special populations 3, 4.
Comparison to Other Treatments
The naltrexone/bupropion combination has been compared to other treatments for weight loss, including placebo and other pharmacological agents.
- The combination therapy has been shown to be more effective than placebo in achieving weight loss and improving health outcomes 2, 3, 4, 5.
- However, the combination therapy has not been directly compared to other pharmacological agents for weight loss, such as orlistat or phentermine/topiramate 3.
Wellbutrin and Natroxelone Combination
Wellbutrin is another name for bupropion, and natroxelone is not a recognized medication.