Understanding the Combination of Bupropion and Naltrexone
Yes, you can take Wellbutrin (the active ingredient is bupropion) and naltrexone together. This combination is not only possible but is formulated into a single, FDA-approved medication called Contrave [1.2.1, 1.2.5]. This extended-release pill is prescribed for chronic weight management in adults who are obese (BMI ≥30) or overweight (BMI ≥27) and have at least one weight-related medical problem, such as high blood pressure or type 2 diabetes [1.2.2]. It is intended to be used alongside a reduced-calorie diet and increased physical activity [1.2.1].
While bupropion and naltrexone are available as separate generic drugs, the specific extended-release formulation and dosage in Contrave (8 mg naltrexone / 90 mg bupropion) were designed to optimize efficacy and minimize side effects for weight management [1.2.2]. Using the individual generic components for weight loss is considered an off-label use and is not supported by the same clinical trial evidence [1.2.2].
How Do Wellbutrin (Bupropion) and Naltrexone Work Together?
The effectiveness of this combination lies in its synergistic effect on the brain's appetite regulation and reward systems [1.3.1]. The exact mechanism is complex, but it targets two key areas:
- The Hypothalamus (Hunger Center): Bupropion, a norepinephrine-dopamine reuptake inhibitor, stimulates pro-opiomelanocortin (POMC) neurons. These neurons release a substance that decreases appetite and increases energy expenditure. However, they also release an opioid (beta-endorphin) that creates a negative feedback loop, dampening the appetite-suppressing effect [1.3.1, 1.3.3].
- The Mesolimbic Reward System: This is where naltrexone, an opioid antagonist, plays its crucial role. It blocks the opioid receptors that beta-endorphin would normally bind to. By blocking this feedback loop, naltrexone allows the appetite-suppressing signal from the bupropion-stimulated POMC cells to remain active for a sustained period [1.2.3, 1.3.1]. This dual action helps reduce hunger and control food cravings [1.2.4].
Efficacy: What Do the Studies Show?
Clinical trials have demonstrated significant weight loss with the naltrexone-bupropion combination compared to placebo.
In a pooled analysis of several phase 3 trials, patients taking the combination medication who were identified as "early responders" (losing ≥5% of body weight by week 16) went on to achieve an average body weight reduction of 11.7% by week 56 [1.6.3]. Across multiple studies, significantly more participants taking the combination achieved at least a 5% weight loss at one year compared to those taking a placebo [1.6.1]. For instance, one major trial showed 6.1% weight reduction for the treatment group versus 1.3% for placebo at 56 weeks [1.2.2]. When combined with intensive behavioral modification, the results were even more pronounced: 9.3% weight loss with the medication versus 5.1% with behavioral modification alone [1.2.2].
Important Safety Information and Side Effects
Like all medications, the combination of naltrexone and bupropion carries risks and potential side effects.
Common Side Effects: The most frequently reported side effects include nausea, constipation, headache, vomiting, dizziness, insomnia (trouble sleeping), and dry mouth [1.4.5]. Nausea is particularly common, affecting up to 32.5% of users, but these symptoms often decrease over time [1.4.4, 1.2.2].
Serious Warnings (Boxed Warning): Bupropion, as an antidepressant, carries an FDA-boxed warning about an increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults (under 25) [1.5.2, 1.2.1]. All patients should be monitored for worsening depression or unusual changes in behavior, especially when starting the medication or changing the dose [1.4.4].
Who Should NOT Take This Combination (Contraindications): This medication is not safe for everyone. It is contraindicated in patients with:
- Uncontrolled high blood pressure [1.5.3]
- A history of seizure disorders [1.5.3]
- Anorexia or bulimia nervosa, due to an increased risk of seizures [1.5.3]
- Those undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs [1.5.2]
- Chronic opioid use, as naltrexone can precipitate severe opioid withdrawal [1.5.3]
- Use of monoamine oxidase inhibitors (MAOIs) within the last 14 days [1.5.4]
- Pregnancy [1.5.3]
Comparison Table: Individual vs. Combination Therapy
| Feature | Wellbutrin (Bupropion) | Naltrexone | Contrave (Naltrexone/Bupropion) |
|---|---|---|---|
| Primary FDA-Approved Use | Depression, Smoking Cessation [1.7.1] | Opioid & Alcohol Use Disorders [1.8.3] | Chronic Weight Management [1.2.5] |
| Mechanism of Action | Norepinephrine-dopamine reuptake inhibitor [1.7.4] | Opioid antagonist [1.8.3] | Synergistic action on hypothalamus and reward system to reduce appetite and cravings [1.3.1] |
| Common Side Effects | Insomnia, dry mouth, headache, nausea [1.7.4] | Nausea, headache, dizziness, fatigue [1.8.2] | Nausea, constipation, headache, vomiting, dizziness [1.4.5] |
| Use for Weight Loss | Modest weight loss observed, but not FDA-approved for this purpose alone [1.2.3] | Not established as effective for weight loss on its own [1.2.2] | FDA-approved specifically for weight loss in conjunction with diet and exercise [1.2.2] |
Conclusion
Taking Wellbutrin (bupropion) and naltrexone together is a recognized and clinically validated treatment for weight management, available under the brand name Contrave. The combination works synergistically to suppress appetite and control cravings by targeting key brain pathways involved in hunger and reward. While effective for many, it is not without significant risks and contraindications, including a boxed warning for suicidal thoughts and a serious risk of seizures and opioid withdrawal. A thorough discussion with a healthcare provider is essential to determine if this medication is a safe and appropriate option for an individual's weight loss journey. This medication must be used as part of a comprehensive plan that includes diet and exercise [1.2.4].
For more information from the manufacturer, visit the official Contrave® website.
