Naltrexone and bupropion
A daily tablet combining naltrexone, an opioid blocker, with bupropion, an antidepressant. Contrave is the FDA-approved brand.
Brand names: Contrave
Naltrexone and bupropion (known as Contrave, Mysimba)
Also searched as: naltrexone bupropion extended-release.
Educational information. This page does not give dosing instructions or tell you what to take. Ask a prescriber about your own care.
In plain English
Contrave combines two older medicines in one extended-release tablet. Naltrexone blocks opioid receptors and is used for opioid and alcohol dependence. Bupropion is an antidepressant also used to quit smoking. Together they act on the brain's appetite and reward circuits. Neither acts on GLP-1.
In the main 56-week trial (COR-I), adults on the marketed amount lost about 6% of body weight on average, versus about 1% on placebo. Half the participants stopped before the end, and the label reports that 24% stopped because of side effects, mostly nausea.
It carries a boxed warning because bupropion is an antidepressant, and it cannot be used with opioid pain medicines or with a history of seizures.
Brand names and products
A generic name identifies the drug itself. A brand name identifies one company's product. One drug can come in several products with different forms and approved uses, so the brand name often tells you more about what a prescription is for.
| Brand name | Maker | Form | U.S. approved use | Status |
|---|---|---|---|---|
| Contrave | Currax Pharmaceuticals LLC | Daily tablet | Weight management | FDA-approved for weight management |
Approved and investigational. Each product above is approved only for the use shown. Contrave is FDA-approved for chronic weight management. That approval covers this product and its labeled uses only, not every use of naltrexone or bupropion.
How it works
Bupropion is thought to stimulate appetite-suppressing neurons in the hypothalamus, and naltrexone is thought to prevent the brain from damping that signal through its own opioid feedback loop. The label describes the exact mechanism of weight loss as not fully understood.
Forms and approval status
| Form | How it is taken | U.S. status |
|---|---|---|
| Naltrexone and bupropion extended-release tablets (Contrave) | Daily, with a gradual build-up over several weeks. Daily tablet with a gradual build-up. Follow the label and your prescriber. Tell the prescriber about any opioid, seizure or mental-health history first. | Approved in the U.S. as an add-on to a reduced-calorie diet and more physical activity for long-term weight reduction in adults with obesity, or overweight plus at least one weight-related condition. Not approved for children. |
What the trials found
These are group averages from published trials in adults without diabetes unless stated. See how to read trial numbers before comparing.
COR-I
Average change in body weight. Every bar uses one scale, 0 to 25 percent.
- People studied
- 1,742 adults with obesity, or overweight plus high cholesterol or high blood pressure
- Length
- 56 weeks
- Compared with
- Placebo, with a mild reduced-calorie diet and exercise advice in all groups
- What was measured
- Average change in body weight at week 56
- Analysis approach
- Last observation carried forward, in participants with a starting and at least one later weight
- Other results
- Weight loss of at least 5%: 48% (32 mg group) and 39% (16 mg group) vs 16% with placebo. Only about half of participants (50%) completed 56 weeks.
- Safety
- Nausea was the most common side effect: 29.8% (32 mg group) and 27.2% (16 mg group) vs 5.3% with placebo. Headache, constipation, dizziness, vomiting and dry mouth were also more frequent. Blood pressure rose slightly at first, then fell slightly below the starting level. Depression and suicidality events were not higher than with placebo.
- Limits
- Funded by the manufacturer. Half of participants did not finish, so the average depends on how missing data were handled. The marketed Contrave amount matches the 32 mg group. Group averages do not predict one person's result.
Sources: Greenway FL 2010
Safety
Based on the FDA-approved label for Contrave. The official label is the controlling source for warnings. The points below are a summary and may be incomplete.
Boxed warning and label notes
- Naltrexone and bupropion extended-release tablets (Contrave): Boxed warning: antidepressants such as bupropion raise the risk of suicidal thoughts and behavior in children, adolescents and young adults. Contrave is not approved for depression or for anyone under 18.
Warnings labels describe
- Boxed warning for suicidal thoughts and behavior, because bupropion is an antidepressant. Mood should be monitored closely.
- Not for anyone with a seizure disorder, uncontrolled high blood pressure, an eating disorder such as anorexia or bulimia, or who uses opioids or is withdrawing from alcohol, benzodiazepines or anti-seizure drugs.
- Naltrexone blocks opioid medicines. Trying to override that block can cause a fatal overdose.
- Can raise blood pressure and heart rate, trigger mania, cause angle-closure glaucoma, and rarely harm the liver.
Most common in trials
- Nausea
- Constipation
- Headache
- Vomiting
- Dizziness
- Insomnia
- Dry mouth
- Diarrhea
Less common but serious
- Suicidal thoughts and behavior
- Seizures (about 0.1% in trials vs 0% on placebo)
- Raised blood pressure and heart rate
- Severe allergic and skin reactions
- Liver problems
- Mania or hypomania
What is still unknown
- Whether it lowers the risk of heart attacks and strokes. The label says this has not been established.
- How results hold over several years, since many trial participants stopped early.
- How it compares directly with the GLP-1 medicines. No head-to-head trial is recorded in this atlas.
Compiled from public information: FDA-approved labels, manufacturer websites, ClinicalTrials.gov and published journal articles. Sources are listed at the bottom of this page.
Sources
- Contrave (naltrexone and bupropion extended-release) tablets: prescribing information Currax Pharmaceuticals LLC (listed on DailyMed as Nalpropion Pharmaceuticals LLC), on DailyMed (U.S. National Library of Medicine). FDA-approved label revised 11/2025. Official FDA label on DailyMed
- DailyMed: current FDA drug labels U.S. National Library of Medicine. Regulator
- Drugs@FDA: approved drug products U.S. Food and Drug Administration. Regulator
- Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I) Greenway FL, et al. Lancet. 2010;376(9741):595-605. PMID 20673995. Funding: Orexigen Therapeutics. Journal article