Contrave for Weight Loss in Adults
Primary Recommendation
Contrave (naltrexone 32 mg/bupropion 360 mg extended-release) should be used with lifestyle modifications in adults with obesity (BMI ≥30) or overweight (BMI ≥27) with weight-related complications, following a gradual dose escalation protocol starting with one tablet daily and increasing weekly to a target of two tablets twice daily. 1
Mechanism of Action
- Contrave combines naltrexone (opioid receptor antagonist) and bupropion (dopamine/norepinephrine reuptake inhibitor) that work synergistically by activating pro-opiomelanocortin (POMC) neurons in the hypothalamus 1, 2
- Bupropion stimulates POMC neurons while naltrexone blocks opioid-mediated autoinhibition, leading to release of alpha-melanocyte-stimulating hormone, which reduces appetite and increases satiety 1, 2
- This dual mechanism reduces food cravings and improves control of eating behaviors 2
Dosing Protocol
Standard Escalation Schedule
- Week 1: One 8mg/90mg tablet once daily in the morning 1, 3
- Week 2: One tablet twice daily (morning and evening) 1, 3
- Week 3: Two tablets in the morning, one tablet in the evening 1, 3
- Week 4 onward: Two tablets twice daily (maximum dose: 32mg naltrexone/360mg bupropion daily) 1, 2
Discontinuation Criteria
- Discontinue if less than 5% weight loss achieved after 12 weeks at maximum dose 1, 3, 2
- Gradual dose escalation minimizes adverse effects including nausea, constipation, headache, and dizziness 3, 2
Expected Weight Loss Outcomes
- Mean weight loss of 4.8-6.5% at 56 weeks compared to 1.2-1.9% with placebo 2, 4
- 36-57% of patients achieve ≥5% total body weight loss 3, 2
- Average absolute weight loss of approximately 11-22 lbs (5-9 kg) across clinical trials 5
- Weight loss is less than phentermine/topiramate (6.7-8.9 kg) and liraglutide (5.8-5.9 kg), but allows for long-term use unlike short-term phentermine 3, 2
Absolute Contraindications
- Uncontrolled hypertension 1, 3
- Seizure disorders or conditions that increase seizure risk 1, 3, 2
- Current opioid use (naltrexone blocks opioid effects and precipitates withdrawal) 1, 3
- Eating disorders (anorexia nervosa or bulimia) 2
- Pregnancy 3
- Use of MAO inhibitors within 14 days 2
Monitoring Requirements
Blood Pressure and Heart Rate
- Monitor periodically, especially during the first 12 weeks of treatment 1, 3
- Initial transient increase of approximately 1.5 mm Hg in systolic and diastolic blood pressure may occur, followed by reduction below baseline 6
- No increased cardiovascular risk compared to placebo based on systematic review of MACE events 7
Weight Assessment
- Evaluate weight loss at 12 weeks to determine continuation 3, 2
- Monitor cardiometabolic markers including lipids and glucose 5, 4
Common Adverse Effects
- Nausea (29.8%) - most common, generally mild to moderate and transient 2, 6
- Constipation, headache, vomiting, dizziness, and dry mouth 2, 6
- No increased risk of depression or suicidality compared to placebo 4, 6
- Slower dose titration effectively manages gastrointestinal side effects 1
Special Clinical Considerations
Preferred Patient Populations
- Patients with comorbid depression (bupropion is the only antidepressant consistently shown to promote weight loss) 2
- Patients attempting smoking cessation 1, 2
- Patients with alcohol use disorder 2
Caution Required
- Use with extreme caution in patients at increased seizure risk 3
- Ensure patients are not taking opioid medications concurrently 3
- Women of reproductive age must use reliable contraception 3
Switching from Other Weight Loss Medications
- When transitioning from phentermine: Discontinue phentermine immediately and start Contrave the next day using standard dose escalation protocol (no washout period required) 3
- Unlike phentermine (contraindicated in cardiovascular disease), Contrave does not show increased cardiovascular risk 3