Contrave (Naltrexone / Bupropion ER)

Contrave is an extended-release combination of naltrexone and bupropion, FDA-approved September 10, 2014, targeting central nervous system pathways rather than hormonal mechanisms -- uniquely suited for patients with food reward-driven eating behaviors. Bupropion (dopamine/norepinephrine reuptake inhibitor) activates POMC neurons in the hypothalamus, stimulating melanocyte-stimulating hormone to suppress appetite. Naltrexone (opioid receptor antagonist) blocks opioid autoinhibition on POMC neurons -- amplifying bupropion's activation. Naltrexone also blocks mesolimbic dopamine reward signals from eating calorie-dense foods. This dual-pathway approach addresses both homeostatic (hunger) and hedonic (food reward) components simultaneously -- mechanistically distinct from GLP-1 therapies. In COR-II (N=1,496, 56 weeks), patients lost 6.4% body weight vs 1.2% placebo; 50.5% achieved 5%+ weight loss (vs 17.1% placebo). COR-BMOD added intensive behavioral modification reached 9.3% weight loss. COR-DM showed 5% weight loss in T2DM patients. Side effects: nausea (30%), constipation (19%), headache (18%), increased blood pressure and heart rate. Bupropion carries FDA black box warning for suicidal thoughts/behaviors. Contraindicated with: opioid use (naltrexone blocks opioids), seizure disorder, uncontrolled hypertension, MAOI use, eating disorders. Cost: ~$99/month with manufacturer savings card; widely covered by commercial insurance.