Contrave (naltrexone/bupropion): central appetite control and outcomes

Contrave combines two established medicines: naltrexone, an opioid receptor antagonist, and bupropion, a norepinephrine–dopamine reuptake inhibitor. Together they act on hypothalamic and mesolimbic pathways that influence hunger, fullness, and food reward. In Canada, Contrave is approved as an adjunct to reduced-calorie diet and increased physical activity for adults with BMI 30 or more, or 27 or more with a weight-related comorbidity. The labeled maintenance dose is two tablets twice daily after a four-week uptitration.

The pivotal trials were large, year-long studies. COR-I randomized overweight and obese adults to naltrexone/bupropion or placebo with lifestyle advice. Mean loss favored active treatment and more participants achieved at least 5 percent and 10 percent reductions. A companion program with structured behavioral modification showed similar benefits. These are modest absolute numbers compared with GLP-1 and dual-incretin drugs, but the effect is consistent and meaningful for patients who cannot access or tolerate injectables or who prefer an oral option.

How it is used matters. The drug works best when you support structure around meals, sleep, and step count, and when you set early review points. If patients have not lost at least 5 percent of baseline weight by 12 to 16 weeks at the maintenance dose, the label recommends discontinuation because long-term success is unlikely. That rule prevents prolonged exposure without benefit. If the target is met and tolerability is good, continue with periodic reassessment.

Safety: Bupropion lowers seizure threshold. The drug is contraindicated in seizure disorders, bulimia or anorexia nervosa, and in abrupt discontinuation of alcohol, benzodiazepines, or antiepileptics. It is contraindicated with chronic opioid use because naltrexone can precipitate withdrawal. Blood pressure and heart rate can rise, especially early, so monitor in patients with hypertension. Neuropsychiatric warnings reflect bupropion’s antidepressant class; screen for mood changes and suicidality and avoid use with other bupropion-containing products. Counsel on nausea, headache, constipation, dizziness, and insomnia, which are common during uptitration and often fade.

Positioning it in practice. Contrave is reasonable for adults who need an oral agent, prefer to avoid injectables, and have no contraindications. It can pair with structured behavioral programs and with metformin in insulin-resistant patients. Avoid in patients on chronic opioids or with seizure risk. If a patient is already on bupropion for mood or smoking cessation, do not duplicate bupropion; reconsider the plan. If weight loss stalls after an initial response, check sleep, alcohol, and steps before switching agents.

Monitoring. Track weight every two weeks, home blood pressure, pulse, and adherence. Ask about cravings, late-night eating, and sleep quality; these often improve first when the medication is effective. Reinforce resistance training and higher-protein meals to protect lean mass.

Expectations. Compared with GLP-1 or dual-incretin therapies, absolute weight loss is smaller. But patients who respond can maintain a 5 to 10 percent reduction with continued use and supportive habits. That is enough to improve blood pressure, triglycerides, and glycemic markers for many. Decisions should be revisited at regular intervals, not left to autopilot.

References

1. Contrave Product Monograph (Canada). bauschhealth.ca

2. CADTH Clinical Review and Recommendation. NCBI+1

3. Greenway FL et al. COR-I. Lancet 2010. PubMed

4. Apovian CM et al. Phase 3 NB trial. Obesity 2013. PMC

5. CDR Clinical Review Report (dose escalation and outcomes). Cda-amc