Naltrexone-bupropion (Contrave)

What it treats

Contrave is approved by the U.S. Food and Drug Administration for chronic weight management in adults with a BMI of 30 or greater, or a BMI of 27 or greater with at least one weight-related condition (hypertension, dyslipidemia, type 2 diabetes), as an adjunct to a reduced-calorie diet and increased physical activity.

Average weight loss in trials was in the range of 4 to 5% of body weight over a year, more in patients who kept coming to follow-up. It sits behind GLP-1 medications (semaglutide, tirzepatide) in efficacy for most patients, but it can be a good match for someone who can't use GLP-1s, wants an oral option, or has depression that might also respond to bupropion.

How it works

The two components target appetite through complementary paths.

Bupropion (an NDRI) activates POMC neurons in the hypothalamus, which release melanocortins that reduce appetite. It's also an antidepressant, and some of the food-craving and mood component of weight regulation overlap.

Naltrexone, at the lower dose used here (32 mg per day total), blocks an autoinhibitory feedback loop on POMC neurons. That amplifies bupropion's effect on appetite regulation. It also blunts the reward from highly palatable foods (the same mechanism that makes alcohol less rewarding at the higher naltrexone dose used in alcohol use disorder).

Together they reduce appetite and quiet food-related reward. The mood and energy effect of bupropion is a real second story for patients who have low mood or low motivation to move.

Receptor mechanism (detail)

The combination pairs two mechanisms:

• Naltrexone. Competitive antagonist at the µ-opioid receptor, with weaker κ and δ activity. In this product it's used at a lower total daily dose (32 mg) than in alcohol or opioid use disorder.
• Bupropion. Norepinephrine and dopamine reuptake inhibitor. Increases synaptic dopamine and norepinephrine in reward and appetite-regulating circuits, including the arcuate nucleus of the hypothalamus.

The naltrexone-bupropion interaction on POMC neurons is the specific rationale for combining them for weight loss.

Potency and typical dosing pattern

Ranges are typical framework only, not a prescription for any individual.

Contrave is titrated over 4 weeks to a target dose of 32 mg naltrexone / 360 mg bupropion per day, divided as 2 tablets twice daily. Each tablet contains 8 mg naltrexone and 90 mg bupropion sustained-release.

Standard titration:

• Week 1: 1 tablet in the morning.
• Week 2: 1 tablet twice a day.
• Week 3: 2 tablets in the morning, 1 tablet in the evening.
• Week 4 onward: 2 tablets twice a day.

Doses shouldn't be crushed or split. Take with food (though not a high-fat meal, which raises absorption).

Response is assessed at 12 to 16 weeks. If a patient hasn't lost at least 5% of baseline body weight by that point, guidelines recommend stopping.

Safety monitoring

• Blood pressure and heart rate. Bupropion can raise both. Baseline BP, and periodic checks (especially in the first months). Uncontrolled hypertension is a contraindication.
• Suicidality (bupropion boxed warning). Bupropion carries the antidepressant class boxed warning. Ask about mood and thoughts of self-harm, especially in the first weeks and in younger patients.
• Seizure risk. Bupropion lowers seizure threshold. Any history of seizure, bulimia, anorexia, or abrupt alcohol or sedative withdrawal is a contraindication.
• Liver function. LFTs at baseline and if symptoms arise. Naltrexone can cause hepatotoxicity, though the dose here is lower than the addiction indication.
• Opioid use. Any current or recent opioid use is a contraindication. Opioid-dependent patients can be precipitated into withdrawal.
• Contraception counseling. If a patient might need opioids for pain (planned surgery, procedure, injury), the naltrexone component matters. Also, women of reproductive age should be counseled about pregnancy risk with weight-loss medications.
• Glaucoma. Angle-closure risk with bupropion. Screen with a low threshold.

What to expect

Common side effects

• Nausea (the most common reason for discontinuation).
• Constipation.
• Headache.
• Vomiting.
• Dizziness.
• Insomnia.
• Dry mouth.
• Diarrhea in some.
• Blood pressure or heart rate rise.

Slow titration and taking doses with food help with nausea.

Serious side effects and warnings

• Suicidality (bupropion boxed warning). Antidepressant class warning applies. Watch for new or worsening mood, agitation, or thoughts of self-harm, especially in younger patients and early in treatment.
• Seizures. Bupropion lowers seizure threshold. Contraindicated in seizure disorder, bulimia, anorexia, and abrupt alcohol or sedative withdrawal.
• Hypertension. Bupropion can raise blood pressure. Uncontrolled hypertension is a contraindication.
• Precipitated opioid withdrawal. Any current opioid use is a contraindication.
• Hepatotoxicity. Reported with naltrexone. LFTs if symptoms.
• Angle-closure glaucoma. Bupropion can precipitate it in susceptible patients.
• Serotonin syndrome. Rare, but has been reported when combined with serotonergic drugs, especially MAOIs (contraindicated) and high-dose SSRIs.
• Bupropion-related activation. Anxiety, insomnia, agitation.
• Manic switch in patients with underlying bipolar disorder.

Sexual and relational effects

Bupropion, on average, has a favorable sexual side effect profile compared with SSRIs, and some patients notice improved libido or arousal on it. Naltrexone at the low doses used here doesn't have a prominent sexual side effect. The relational conversation with weight-loss medication is bigger than side effects: family and household eating patterns, exercise routines, and the emotional weight of chronic weight management all show up. Medication is a tool inside those systems, not a fix for them.

Weight, appetite, and sleep

The whole point is weight and appetite. Average trial weight loss was 4 to 5% at a year, better in those who kept up with lifestyle changes. Appetite reduction and quieter food reward are the mechanisms.

Sleep is often disrupted early. Bupropion is activating and can cause insomnia. Taking the evening dose earlier in the afternoon sometimes helps.

Starting and dosing basics

This section is general background, not a dosing instruction for any individual.

The built-in 4-week titration exists because starting at the full dose is poorly tolerated. Take tablets whole, with food, but not with high-fat meals (which raise bupropion absorption and seizure risk).

Response assessment at 12 to 16 weeks is standard: at least 5% weight loss to continue.

Contrave is contraindicated with MAOIs, in uncontrolled hypertension, in seizure disorder, in bulimia or anorexia, in current opioid use or opioid use disorder on opioid agonist therapy, in acute alcohol or sedative withdrawal, and in pregnancy.

Missed doses and interactions

If a morning dose is missed, skip it and take the next scheduled dose. Don't double up. Missing multiple doses means the titration effectively restarts if the gap is long enough.

Interactions that matter:

• MAOIs. Contraindicated. At least 14 days between MAOI and Contrave.
• Opioids. Contraindicated. Blocked and can precipitate withdrawal in dependent patients.
• Other bupropion-containing products. Additive seizure risk.
• Drugs that lower seizure threshold. Tramadol, theophylline, systemic corticosteroids, some antipsychotics.
• CYP2B6 inducers and inhibitors can shift bupropion levels.
• CYP2D6 substrates. Bupropion is a strong CYP2D6 inhibitor. Levels of many antidepressants, antipsychotics, beta blockers, and tamoxifen can rise. Give every prescriber a full list.
• Alcohol. Additive seizure risk with heavy use; abrupt alcohol withdrawal is a contraindication.

Stopping and tapering

Contrave doesn't cause classic physical dependence. It can be stopped without a formal taper, though some clinicians step down over a week or two, especially at the full dose. If it's stopped because of intolerance early in treatment, restarting is possible with slower titration.

For patients who stop after achieving weight loss, weight regain over the following year is common, as it is with any weight-loss medication. This is a longer conversation about whether weight management medication should be treated as chronic therapy the way blood pressure medication is.

Pregnancy and breastfeeding

Contrave is contraindicated in pregnancy. Weight loss during pregnancy isn't recommended. Bupropion has some reproductive data reassurance for depression use, but weight-loss use isn't appropriate in pregnancy. Anyone who is pregnant, planning a pregnancy, or breastfeeding should stop and talk it through with a prescriber.

Cost and generic availability

Contrave is branded and expensive. There's no generic combination product (the individual generics of naltrexone and bupropion SR exist but aren't dosed the same way). Insurance coverage for weight-loss medications varies substantially, and prior authorization is common. Manufacturer savings programs are frequently used.

Common questions

How does this compare to GLP-1 medications? For most patients, GLP-1s (semaglutide, tirzepatide) produce more weight loss on average. Contrave can be a good fit for patients who can't tolerate or access GLP-1s, want an oral option, or have low mood or motivation that might respond to bupropion.

Will this help my depression? Bupropion at antidepressant doses is a separate use of the same molecule. Contrave provides a total daily bupropion dose of 360 mg, which is in the antidepressant range for bupropion SR. Some patients notice mood benefit. That said, treating depression with Contrave isn't the labeled indication, and if depression is the primary problem, plain bupropion or another antidepressant is the cleaner tool.

Can I drink alcohol on this? Light drinking is not automatically dangerous, but bupropion lowers seizure threshold, and abrupt alcohol withdrawal is a contraindication. Heavy drinking is a problem.

What if I need pain medication? Opioid pain medications won't work while naltrexone is on board, even at the lower dose in Contrave. Elective surgery is best planned with the treatment team in advance.

How long should I stay on it? If it's working (at least 5% weight loss at 12 to 16 weeks), long-term use is standard. Stopping usually leads to weight regain.

Questions to ask your prescriber

• What are we hoping this treats, and how will we know it's working?
• How will we track blood pressure?
• What signs of mood change should I watch for?
• What's the plan if I need pain medication for surgery?
• When would we assess whether to keep going or stop?

Sources

This guide draws on current prescribing information and public health references. It is reviewed for clinical accuracy and updated as guidance changes, and current as of June 8, 2026.

• U.S. Food and Drug Administration. Naltrexone HCl/bupropion HCl extended-release (Contrave) prescribing information, including boxed warning.
• DailyMed, U.S. National Library of Medicine. Naltrexone HCl and bupropion HCl extended-release tablets.
• MedlinePlus, U.S. National Library of Medicine. Naltrexone and bupropion.
• The Obesity Society. Position statements on pharmacotherapy for obesity.
• American Association of Clinical Endocrinology. Clinical Practice Guideline for obesity management.