In clinical trials, Contrave produced about 4–6% more weight loss than placebo over a year, with about half of users losing at least 5%.
Looking for a straight, evidence-led read on how this naltrexone/bupropion combo performs in real life? This guide pulls from large randomized trials and official labeling to show what results to expect, who tends to benefit, and where the limits sit.
What Contrave Is And How It Works
Contrave combines two medicines: naltrexone, an opioid receptor blocker, and bupropion, a dopamine/norepinephrine reuptake inhibitor. Together they act on hypothalamic POMC neurons and reward circuits linked to appetite control. The label describes the mechanism and dosing, along with the safety box warning.
Evidence At A Glance: Outcomes You Can Expect
Four phase-3 trials (the COR program) studied more than 4,500 adults for 56 weeks with lifestyle changes on top of medication or placebo. Across trials, average weight loss with the medication ranged near 6–9% of starting weight in completers, with placebo groups near 1–5%; about half of treated participants reached at least 5% loss, compared with about one in five on placebo.
Trial Results Snapshot
| Trial (56 Weeks) | Mean Loss (Active vs Placebo) | ≥5% Loss (Active vs Placebo) |
|---|---|---|
| COR-II | ~6.4% vs ~1.2% | ~50.5% vs ~17.1% |
| COR-BMOD* | ~9.3% vs ~5.1% | Higher in active across thresholds |
| COR-I / COR-DM | Active arms consistently beat placebo | Higher responder rates with active |
*BMOD = structured behavior program layered on top of standard lifestyle advice. Data are from peer-reviewed publications and labeling summaries; exact imputation methods vary by study.
Real-World Takes On Contrave Weight Loss Results
Trial data show two broad patterns. First, response tends to show up early. People who drop weight in the first 12–16 weeks usually keep losing across the year. Second, there is a wide range of outcomes; some lose 10% or more, while others see little change and stop early due to side effects or lack of progress.
What “Effective” Looks Like In Practice
- Meaningful loss: Many responders land near 7–10% loss at a year with steady adherence and lifestyle changes.
- Moderate lift over lifestyle alone: Expect a few extra percentage points beyond diet and activity. That gap matters for blood sugar, blood pressure, and waist size.
- Non-responders exist: If the scale barely moves by week 12 at full dose, the label directs stopping the drug.
Who Benefits Most
The best candidates are adults with BMI ≥30, or ≥27 with conditions like high blood pressure or dyslipidemia, who want an oral option and prefer appetite-control support. People who track intake, attend follow-ups, and stick with the dose ramp often fare better. The label lists the formal indication and the clinical context for use.
Response Rule At Week 12
There’s a clear stop rule: if you haven’t lost at least 5% of baseline body weight after 12 weeks on the maintenance dose, end therapy, since further benefit is unlikely. This protects you from staying on a plan that isn’t delivering.
Dosage, Titration, And Daily Use
Dosing ramps over four weeks to reduce nausea and seizure risk:
- Week 1: 1 tablet in the morning
- Week 2: 1 tablet in the morning, 1 in the evening
- Week 3: 2 in the morning, 1 in the evening
- Week 4 onward: 2 in the morning, 2 in the evening
Each tablet contains 8 mg naltrexone HCl and 90 mg bupropion HCl (extended-release). Avoid high-fat meals with doses.
You can read the full labeling and dosing table in the official FDA document. For clinicians, the medication’s boxed warnings and dosing are detailed with interaction guidance.
Safety, Side Effects, And When To Avoid
Common side effects include nausea, constipation, headache, dizziness, insomnia, dry mouth, and diarrhea. Many fade after the first weeks. A small rise in pulse and blood pressure can occur, so monitoring is advised.
Situations Where This Drug Should Not Be Used
- Uncontrolled hypertension
- Seizure disorder, or a history of seizures
- Use of other bupropion-containing products
- Chronic opioid therapy or acute opioid withdrawal
- Use of MAOIs within the past 14 days
- Current or prior anorexia nervosa or bulimia
- Pregnancy
These are formal contraindications on the label, which also includes a class warning about suicidal thoughts and behaviors with antidepressants in younger people.
Drug Interactions To Know
Bupropion is a CYP2D6 inhibitor; levels of some antidepressants, antipsychotics, beta-blockers, and certain antiarrhythmics can rise. CYP2B6 inhibitors and inducers can alter bupropion exposure. The label advises caution with other agents that lower the seizure threshold, and it flags alcohol sensitivity.
How It Stacks Up Against Other Options
Weight-loss medicines land on a spectrum of efficacy, route, and tolerability. Oral naltrexone/bupropion offers appetite control and cravings reduction. GLP-1-based injectables deliver larger mean losses but come with different risks, costs, and supply realities. Treatment choice sits inside a broader plan that includes nutrition, activity, sleep, and follow-up. A 2024 review in Diabetes Spectrum outlines the tiered approach that pairs lifestyle, medicines, and surgery.
For a clinician-level overview of where each medicine fits, see the guideline-directed approach that summarizes current practice patterns and patient selection.
Setting Expectations: Timeline And Milestones
- Weeks 1–4: Dose ramp; nausea and headache are most common. Early appetite control may appear.
- Weeks 8–12: Progress check; responders often pass the 3–5% mark by now. Apply the 12-week stop rule at full dose.
- Months 6–12: Loss usually levels into a steady slope. Lifestyle consistency shapes the final number.
Managing Side Effects Without Derailing Progress
Simple moves can keep you on track:
- Split meals and keep fat content modest around dosing to lower nausea risk.
- Hydrate well to offset constipation and dry mouth.
- Aim for a steady sleep schedule to reduce insomnia.
- Log blood pressure and pulse at home, then bring readings to visits.
When To Call The Prescriber
Pause dosing and call if you notice mood changes, thoughts of self-harm, seizures, severe headache, vision changes, intense vomiting, chest pain, or sustained high blood pressure readings. This aligns with the label’s warnings and helps catch problems early.
Fit Check: Is This The Right Pick?
| Best Fit | Not A Fit | Reason |
|---|---|---|
| Adults wanting an oral, cravings-focused aid | People with seizure history or uncontrolled BP | Label contraindications and seizure risk |
| Those open to food tracking and follow-ups | Anyone on chronic opioids or recent MAOIs | Opioid blockade and drug-interaction risks |
| Patients fine with modest average losses | People seeking double-digit loss as a baseline | Mean effect is moderate vs some injectables |
Use this as a conversation starter with your clinician, along with medical history and current meds.
Practical Tips To Get Better Results
- Commit to the 12-week test. Track weight weekly, then decide to continue or stop based on the label’s rule.
- Pair with a simple meal plan. A 300–500 kcal daily deficit plus protein at each meal supports adherence. Trials added lifestyle coaching to every arm.
- Plan around dosing. Take tablets as scheduled; avoid high-fat meals at dose times.
- Monitor vitals. Bring blood pressure and pulse logs to visits.
- Match the tool to the goal. If you need larger average loss or have diabetes benefits in mind, your clinician may compare this pill with GLP-1-based options.
Bottom Line On Effectiveness
Across one year, this medication adds a modest but clinically useful bump over lifestyle alone. About half of users reach at least 5% loss, and a sizable subset pass 10%. Response shows early, so you won’t wait long to see if it’s helping. Safety screening matters; the label lists clear do-not-use situations and interaction steps. If you match the profile and prefer an oral route, it’s a sound option to trial with follow-up and a clear off-ramp if the scale doesn’t budge.
Method Notes
Figures in this guide come from peer-reviewed COR trials and the official label. Where ranges are given, they reflect different analytic sets or completer vs. modified intention-to-treat results in those publications.