The Wellbutrin Naltrexone combination unites bupropion (Wellbutrin) and naltrexone. This combination therapy leverages the strengths of each component to address specific health conditions.
Understanding the Individual Components
Bupropion (Wellbutrin) is an atypical antidepressant prescribed for major depressive disorder and seasonal affective disorder. It also aids smoking cessation (e.g., Zyban).
Naltrexone is an opioid antagonist, blocking opioid effects in the brain. It primarily manages alcohol use disorder and opioid dependence, reducing cravings for alcohol and opioids and diminishing their rewarding effects.
The Combined Mechanism of Action
The combination of bupropion and naltrexone works through a complementary mechanism, particularly in regulating appetite and food cravings. Bupropion acts as a weak inhibitor of dopamine and norepinephrine reuptake, leading to increased activity of pro-opiomelanocortin (POMC) neurons in the hypothalamus. These POMC neurons produce alpha-melanocyte-stimulating hormone (alpha-MSH) and beta-endorphin.
Naltrexone, an opioid antagonist, blocks the mu-opioid receptors on these same POMC neurons. Beta-endorphin typically exerts an inhibitory feedback on POMC cells by binding to these receptors. By blocking this inhibitory feedback, naltrexone amplifies the stimulatory effect of bupropion on POMC neurons, leading to an enhanced release of alpha-MSH. This combined action promotes satiety, reduces food intake, increases energy expenditure, and affects the brain’s reward pathways to reduce food cravings.
Prescribed Uses for the Combination
The fixed-dose combination of naltrexone and bupropion, known as Contrave, is approved for chronic weight management in adults. This medication is prescribed as an adjunct to a reduced-calorie diet and increased physical activity. It is indicated for individuals with an initial body mass index (BMI) of 30 kg/m2 or greater.
The combination is also approved for overweight adults, defined as having a BMI of 27 kg/m2 to less than 30 kg/m2, provided they also have at least one weight-related comorbidity. These include type 2 diabetes, dyslipidemia (abnormal lipid levels in the blood), or controlled high blood pressure.
Patient Considerations and Warnings
Patients should be aware of important considerations and potential warnings. Common side effects include nausea, vomiting, diarrhea, constipation, headache, dizziness, dry mouth, and insomnia. Increased blood pressure and heart rate may also occur, requiring regular monitoring.
Serious warnings include an increased risk of seizures, especially with a history of seizure disorders, eating disorders, or concurrent bupropion use. Liver problems, such as upper stomach pain, dark urine, or yellowing skin/eyes, can occur; seek immediate medical attention if these appear. The medication is contraindicated in individuals with uncontrolled high blood pressure, severe hepatic impairment, or during acute opioid withdrawal. It should not be used within 14 days of taking a monoamine oxidase inhibitor (MAOI) due to the risk of severe reactions.
Dosing typically begins with one tablet (8 mg naltrexone/90 mg bupropion) once daily for the first week. It is gradually increased over several weeks to a maintenance dose of two tablets twice daily (totaling 32 mg naltrexone/360 mg bupropion per day). Tablets should be swallowed whole and not crushed, chewed, or cut. Alcohol consumption should be limited or avoided during treatment due to potential interactions and increased risk of side effects. Consultation with a healthcare provider is important to ensure proper administration, monitor for side effects, and assess suitability.