Contrave (naltrexone-bupropion)
NOT a GLP-1. Combination naltrexone + bupropion oral pill for weight loss.
Contrave is not a GLP-1 medication. It is a fixed-dose oral combination of naltrexone (an opioid antagonist) and bupropion (a dopamine/norepinephrine reuptake inhibitor) approved by the FDA in 2014 for chronic weight management. Average weight loss: 5-9%.
Overview
Contrave addresses weight loss through different mechanisms than GLP-1s. Naltrexone blocks opioid receptors involved in food reward; bupropion increases dopamine and norepinephrine, supporting appetite regulation in the hypothalamus. The combination is more effective than either drug alone.
How Contrave Works
Naltrexone blocks opioid-mediated reward signaling around food. Bupropion increases noradrenergic and dopaminergic tone in appetite-regulating brain regions. The combination reduces food cravings and modestly suppresses appetite — without the GI side effects of GLP-1s.
Dosing & Schedule
Contrave is titrated over 4 weeks: 1 tablet morning week 1, 2 tablets daily week 2, 3 tablets daily week 3, 4 tablets daily week 4+ (maintenance: 32 mg naltrexone + 360 mg bupropion daily).
Effectiveness — Trial Data
Trial data: 5-9% weight loss vs. 1.8% placebo at 56 weeks. Less effective than GLP-1s but useful for patients who cannot use GLP-1s (thyroid cancer history, severe GI conditions).
Side Effects
Common: nausea (33%), constipation (19%), headache (18%), insomnia (9%), dizziness, dry mouth. Boxed warning for suicidal thoughts (bupropion). Contraindicated in seizure disorders, eating disorders, opioid dependency.
Cost — How Much Contrave Costs in 2026
$99-650/mo depending on insurance and source. Generic naltrexone-bupropion is available at lower cost via separate prescriptions in some cases.
Who Is Contrave For?
Adults with BMI ≥30 or ≥27 with comorbidity. Particularly useful for patients with contraindications to GLP-1s, or those who prefer an oral option.