Naltrexone, initially used for opioid and alcohol dependence, is now also recognized for weight management. Combined with bupropion, this medication offers a different approach to addressing excess weight. It targets specific pathways within the brain that influence hunger and cravings, complementing diet and exercise efforts.
How Naltrexone Influences Weight
Naltrexone contributes to weight management by acting as an opioid receptor antagonist, blocking certain brain receptors. This action can reduce the pleasure and reward from eating, especially high-calorie foods, lessening cravings. When combined with bupropion, an atypical antidepressant influencing dopamine and norepinephrine, a synergistic effect occurs. This combination, often marketed as Contrave, influences appetite regulation and energy balance within the brain.
Bupropion activates proopiomelanocortin (POMC) neurons in the hypothalamus, which reduce appetite and increase energy expenditure. Endogenous opioids typically inhibit these POMC neurons, creating a negative feedback loop. Naltrexone blocks these opioid receptors, preventing POMC neuron inhibition and enhancing bupropion’s effect on appetite suppression and satiety. This dual action helps to reduce hunger and increase feelings of fullness, impacting food intake and promoting weight loss.
Effectiveness and What to Expect
Clinical trials show that naltrexone and bupropion combined lead to significant weight loss when used with a reduced-calorie diet and increased physical activity. Across four studies, participants treated with naltrexone/bupropion experienced an average weight loss ranging from approximately 11 to 22 pounds (5 to 9 kg) from their baseline weight. Many patients achieved a clinically meaningful weight loss of 5% or more of their initial body weight, with some studies showing 36% to 57% of patients reaching this benchmark, compared to 17% to 43% with placebo.
Weight loss with this medication tends to be sustained, with studies reporting maintenance over 56 weeks. Individual results can vary, and the medication is most effective when integrated into a comprehensive weight management plan. This includes consistent adherence to dietary changes and regular physical activity, which enhance the medication’s benefits. Patients are typically advised to continue therapy for up to one year if they achieve at least 5% weight loss within the first 12 weeks, as this indicates likely continued benefit.
Potential Side Effects and Safety
Like all medications, naltrexone combined with bupropion can cause side effects. Common side effects include nausea, constipation, headache, dizziness, dry mouth, insomnia, vomiting, and diarrhea. These mild side effects often improve as the body adjusts to the medication over time.
More serious, though less common, side effects include an increased risk of high blood pressure and heart rate, seizures, and potential changes in mood or behavior, including suicidal thoughts. The medication is contraindicated in individuals with uncontrolled high blood pressure, a history of seizures, or certain eating disorders like bulimia or anorexia nervosa. It should also not be used by those taking opioid medications or those undergoing acute opioid withdrawal. Patients should discuss their complete medical history, including any mental health conditions, and all current medications with a healthcare provider before starting treatment to ensure safety.
Who Can Use Naltrexone for Weight Loss
Naltrexone, combined with bupropion, is indicated for chronic weight management in adults meeting specific criteria. This typically includes individuals with a body mass index (BMI) of 30 kg/m² or greater, which is categorized as obesity. The medication is also approved for adults with a BMI of 27 kg/m² or greater who have at least one weight-related comorbidity. These comorbidities can include conditions such as type 2 diabetes, high cholesterol (dyslipidemia), or controlled high blood pressure.
This medication is a prescription-only treatment and requires ongoing supervision from a qualified healthcare professional. A thorough medical evaluation is necessary to determine if the medication is appropriate and safe, considering overall health and potential contraindications. The treatment is designed to be an adjunct to, not a replacement for, a reduced-calorie diet and increased physical activity.