Contrave for Weight Loss

Contrave is not a new molecule. It is naltrexone and bupropion, both decades old, locked into one extended-release tablet because of what they do to a single group of brain cells. Bupropion stimulates pro-opiomelanocortin neurons in the hypothalamus, and those neurons then release beta-endorphin, which loops back and shuts them down again. Naltrexone blocks that opioid-mediated autoinhibition, and in mouse recordings the two together drove POMC firing and cut acute food intake more than either drug on its own.

That feedback loop is the whole argument for the combination, and it is why this page is separate from our pages on bupropion for weight loss and naltrexone for weight loss. In a randomized dose-finding trial of 419 adults, the combination separated from naltrexone alone and placebo by week 16 and from bupropion alone by week 24, with no efficacy plateau through 48 weeks. The label is candid that the exact neurochemical effects leading to weight loss are not fully understood.

Four 56-week trials, 4,536 adults, carry the approval. In COR-I the average change was minus 5.4% on the full dose against minus 1.3% on placebo, with 42% versus 17% reaching a 5% loss and 21% versus 7% reaching 10%. COR-BMOD, which layered on 28 group counselling sessions, reached minus 8.1% against minus 4.9%. COR-Diabetes managed minus 3.7% against minus 1.7%. COR-II, run in 1,496 adults, put the 56-week figure at minus 6.4% versus minus 1.2%, with 50.5% reaching a 5% loss.

Read those numbers with the analysis population in mind. The COR-I paper reports minus 6.1% and 48% reaching 5%, because its primary analysis counted only participants still on study drug; the label's lower figures carry everyone who was randomized. About 45% of the placebo group and 46% of the treated group left before week 56, most inside the first 12 weeks. COR-BMOD, the arm that added 28 group counselling sessions, posted the highest average of the four label trials at minus 8.1%, though its placebo arm also moved furthest at minus 4.9%, and COR-Diabetes shows the effect shrinks when type 2 diabetes is in the picture.

Anyone comparing options deserves the unflattering number first. Once-weekly semaglutide 2.4 mg produced a mean 14.9% weight change at 68 weeks against 2.4% on placebo. Tirzepatide produced 15.0%, 19.5% and 20.9% at 5 mg, 10 mg and 15 mg over 72 weeks, with 57% of the top-dose group losing at least 20%.

Contrave's COR-I figure is 5.4%, and the highest single-trial figure anywhere in its record is the 6.4% from COR-II. There is no reading of the trial record in which this tablet matches an injectable incretin on scale.

Magnitude is not the only axis, though. The 2022 American Gastroenterological Association guideline suggests naltrexone-bupropion ER for long-term weight management on moderate certainty evidence, in the same recommendation tier as semaglutide, liraglutide and phentermine-topiramate ER, and recommends against orlistat. It is oral, it is not refrigerated, it does not involve a needle, and it targets craving and reward rather than gastric emptying. Whether that trade is worth making is a conversation for a licensed clinician who knows your history.

The indication is adults with obesity, or overweight with at least one weight-related comorbid condition, always alongside a reduced-calorie diet and increased physical activity. The guideline threshold behind that is a BMI of 30 or greater, or 27 or greater with weight-related complications, after lifestyle change alone has not been enough. Federal health guidance frames every one of these drugs the same way, as an addition to eating and activity changes rather than a replacement for them.

The mechanism points at a specific eating pattern. The combination was designed around reward circuitry and food craving as much as around appetite, and COR-II measured improvements in control of eating alongside weight. If your difficulty is wanting food rather than feeling full, that is the argument. The disqualifiers are hard and are covered further down: any opioid use, any seizure history, and current or past anorexia nervosa or bulimia all rule it out. A clinician decides suitability; nothing here is medical advice.

The escalation runs one extra tablet a week until the full 32 mg / 360 mg dose is reached at the start of week 4: one tablet each morning in week 1, one morning and one evening in week 2, two morning and one evening in week 3, then two and two from week 4 onward. Total daily doses above two tablets twice daily are not recommended. That slow ramp is there because the nausea is dose-related. The drug does not need time to accumulate.

Tablets are swallowed whole and must not be cut, chewed or crushed, since crushing an extended-release bupropion tablet raises the seizure risk. They should not be taken with a high-fat meal, which significantly increases exposure to both components. Moderate or severe renal impairment, moderate hepatic impairment, and concurrent CYP2B6 inhibitors such as ticlopidine or clopidogrel each cap the maximum at two tablets a day, and severe hepatic impairment or end-stage renal disease rule it out.

Across the pooled trials nausea was reported by 32.5% on Contrave against 6.7% on placebo, followed by constipation at 19.2%, headache at 17.6%, vomiting at 10.7% and dizziness at 9.9%. In COR-I nausea affected 29.8% of the full-dose group against 5.3% on placebo, and it was generally mild to moderate and transient. The gap between how many feel it and how many quit over it is the number worth holding on to.

Roughly 24% of the treated group discontinued because of an adverse reaction against 12% on placebo, and the specific reactions driving that were nausea at 6.3%, headache at 1.7% and vomiting at 1.1%. So around one in three felt nauseated and roughly one in sixteen left because of it. The larger LIGHT trial saw gastrointestinal events in 14.2% versus 1.9% and central nervous system symptoms in 5.1% versus 1.2%. Your own tolerance can vary widely, and slowing the titration is a decision for your prescriber.

The boxed warning is headed suicidal thoughts and behaviors, and it flags increased risk in children, adolescents and young adults taking antidepressants. Contrave is not approved for major depressive disorder and is not approved under 18. The obesity trials themselves did not produce that signal: no suicides or suicide attempts were recorded in studies up to 56 weeks, and suicidal ideation was reported by 3 of 1,515 on placebo (0.20%) versus 1 of 3,239 on Contrave (0.03%). COR-I and COR-II both reported no excess depression or suicidality against placebo. The warning is inherited from bupropion's antidepressant record. Contrave did not generate it.

Seizures are the risk that drives the contraindication list. Bupropion can cause seizures and the risk is dose-related; incidence in the trials was about 0.1% against 0% on placebo, and the drug is stopped and not restarted after one. It is contraindicated with a seizure disorder or history of seizures, with current or prior anorexia nervosa or bulimia, during abrupt discontinuation of alcohol, benzodiazepines, barbiturates or antiepileptic drugs, and with any other bupropion-containing product. Serious neuropsychiatric events reported with bupropion during smoking cessation sit in the warnings section rather than the boxed warning.

Contrave is contraindicated with chronic opioid or opiate agonist use such as methadone, with partial agonists such as buprenorphine, and in acute opiate withdrawal. Anyone opioid dependent must be opioid free, tramadol included, before starting, or the naltrexone can precipitate a withdrawal severe enough to need hospital care. Sensitivity to opioids is raised after stopping, and attempting to overcome the blockade with large opioid doses risks respiratory arrest and circulatory collapse.

This one is not a caution to weigh. It is a gate.

Blood pressure and heart rate can rise, so both are measured before treatment and monitored afterwards, and uncontrolled hypertension is a contraindication. Mean blood pressure ran about 1 mmHg above baseline at weeks 4 and 8 while placebo ran 2 to 3 mmHg below, giving treatment differences of 1.8 to 2.4 mmHg systolic in the first 12 weeks. The LIGHT cardiovascular outcomes trial in 8,910 adults was terminated early after the sponsor released confidential interim data, so cardiovascular safety was never established and the label carries that as a stated limitation of use.

Drugs@FDA lists one abbreviated application for naltrexone hydrochloride and bupropion hydrochloride extended-release tablets, and its marketing status is tentative approval, which does not permit marketing. The only approved and marketed product remains the brand under NDA 200063. That single fact explains most of what you will see at the pharmacy counter: with no marketed generic there is no price competition, and there is no national generic acquisition benchmark to quote against. For a grounded reference point, Medicare Part D spending data for 2024 puts average spending at $4.98 per dosage unit across 2,365 claims for 824 beneficiaries, at an average of $806.61 per claim. A dosage unit is one tablet and the maintenance dose is four tablets a day, so that is what a payer records rather than what you would hand over.

Cash prices, manufacturer programs and telehealth bundles all sit outside that dataset, and we do not publish a single monthly figure we cannot verify against a live source.

A telehealth service that prescribes this responsibly asks about seizures, head injury, eating disorders, alcohol and sedative use, and every opioid including tramadol, then records a baseline blood pressure and pulse. Uncontrolled hypertension is a contraindication, and the drug can raise pressure and heart rate. That reading is part of prescribing rather than an optional extra. Judge a service on whether it collects that history and schedules follow-up, rather than on how fast it can ship. Eligibility is a prescriber's call, made on that history and that reading.

There is a built-in stopping rule, and it is unusually specific. Response is evaluated after 12 weeks at the maintenance dose, which is week 16 counting from your first tablet, and if you have not lost at least 5% of starting body weight the drug is discontinued because continued treatment is unlikely to achieve meaningful weight loss. The medication guide repeats the same rule as a 16 week check. This page is information, not medical advice. Agree that week 16 review with your prescriber before the first tablet, because it is the date the label stops being a schedule and becomes a decision.