Naltrexone + Bupropion

What the evidence says

Extended-release naltrexone/bupropion combines an opioid antagonist with an antidepressant also used for smoking cessation. It is approved as an adjunct to reduced-calorie intake and physical activity for adults with obesity, or overweight plus a weight-related condition.^[1]

A systematic review of four pivotal trials and 4,536 participants found about 2.5 kg more weight loss than placebo and an approximate number needed to treat of five for at least 5% loss. It also found more adverse events, serious adverse events, and treatment discontinuation, with low certainty for much of the benefit estimate.^[2]

A broader 2024 meta-analysis found the combination more effective than bupropion alone, while contemporary anti-obesity-drug reviews place its average efficacy below injectable GLP-1 or dual-agonist options. Individual response varies, and the label instructs stopping if at least 5% baseline weight has not been lost after 12 weeks on the maintenance dose.^[3][4][1]

It cannot be used with chronic opioids or during acute opioid withdrawal, uncontrolled hypertension, seizure disorders, eating disorders, MAO inhibitors, pregnancy, or another bupropion-containing product. It can raise blood pressure and heart rate, and the bupropion component carries an antidepressant boxed warning for suicidal thoughts and behaviors in younger people.^[1][5]