Contrave for Weight Loss: Clinical Guidelines and Usage
Primary Recommendation
Contrave (naltrexone 8mg/bupropion 90mg extended-release) should be used with lifestyle modifications in adults with obesity or overweight with weight-related complications, following a specific dose escalation protocol starting with one tablet daily and increasing weekly to a target of two tablets twice daily (32mg/360mg total daily dose). 1
Dosing Protocol
Standard Escalation Schedule
- Week 1: One tablet (8mg/90mg) once daily in the morning 1, 2
- Week 2: One tablet twice daily (morning and evening) 1
- Week 3: Two tablets in the morning, one tablet in the evening 1
- Week 4 onward: Two tablets twice daily (morning and evening) - maximum dose of 32mg naltrexone/360mg bupropion 1, 2
This gradual titration minimizes adverse effects including nausea, constipation, headache, and dizziness 2
Mechanism of Action
Contrave works through dual complementary pathways:
- Bupropion component: Inhibits dopamine and norepinephrine reuptake, modulating central reward pathways triggered by food consumption 3
- Naltrexone component: Antagonizes an inhibitory feedback loop, enhancing the overall effect on food reward systems 3
- Combined effect: Activates pro-opiomelanocortin (POMC) neurons in the arcuate nucleus, causing release of alpha-melanocyte-stimulating hormone, a potent anorectic neuropeptide that projects to hypothalamic areas controlling feeding and body weight 1, 3
This mechanism makes Contrave particularly effective for patients with food cravings and food addiction-like behaviors 3
Expected Outcomes and Efficacy Assessment
Weight Loss Results
- Mean weight loss of 4.8-5.0% at 56 weeks compared to placebo 2, 3
- 36-57% of patients achieve ≥5% total body weight loss 2, 3
- Average weight loss across clinical trials: 11-22 lbs (5-9 kg) 4
Critical Decision Point at 12 Weeks
Discontinue Contrave if the patient has not achieved 5% weight loss at 12 weeks, as continued use is unlikely to provide meaningful benefit. 1, 2, 3
Absolute Contraindications
Contrave must be avoided in patients with:
- Seizure disorders or conditions that increase seizure risk 1, 2
- Current opioid use - naltrexone will block opioid effects and precipitate withdrawal in opioid-dependent individuals 1, 2
- Uncontrolled hypertension 1, 2
- Pregnancy - women of reproductive age must use reliable contraception 2, 5
- MAO inhibitor use within 14 days 3
- History of eating disorders (bulimia or anorexia nervosa) 2
Monitoring Requirements
Blood Pressure and Heart Rate
Monitor blood pressure and heart rate periodically, especially during the first 12 weeks of treatment, as Contrave can elevate both parameters. 1, 2, 3
Neuropsychiatric Monitoring
Monitor for mood changes, depression, and suicidal ideation, as bupropion carries a black box warning for suicidal thoughts in young adults 3
Cardiovascular Safety
Available evidence does not indicate increased risk of major adverse cardiovascular events (MACE) with Contrave use, unlike phentermine which is contraindicated in cardiovascular disease 2, 6
Preferred Patient Populations
Contrave may be preferentially considered for:
- Patients attempting smoking cessation - bupropion is FDA-approved for this indication 1
- Patients with comorbid depression - bupropion has antidepressant properties 1
- Patients with significant food cravings - the combination specifically targets reward pathways 3
- Patients with polycystic ovary syndrome (PCOS) or endometriosis seeking weight loss before conception 5
Common Adverse Effects
The most frequent side effects include:
- Nausea (most common reason for discontinuation) 1, 3
- Constipation 2, 3
- Headache 2, 3
- Dizziness 2, 3
- Insomnia 3
- Dry mouth 3
Approximately half of patients experience gastrointestinal symptoms 3
Switching from Other Weight Loss Medications
From Phentermine to Contrave
Discontinue phentermine immediately and start Contrave the next day using the standard dose escalation protocol - no washout period is required. 2
This is advantageous because Contrave allows for long-term use (unlike phentermine which is FDA-approved only for 12 weeks), produces comparable efficacy, and does not carry the cardiovascular contraindications associated with phentermine 2
Preconception Considerations
For women of reproductive age planning pregnancy:
- Stop Contrave at least 2 months before attempting conception 5
- Contrave can be used with contraception for weight loss in the preconception period 5
- Weight loss of 6% total body weight with Contrave may improve fertility by mitigating effects of PCOS and endometriosis 5
- GLP-1 receptor agonists may be preferred over Contrave for greater weight loss (up to 30% vs 6%) if time permits before conception 5
Metabolic Benefits Beyond Weight Loss
Clinical trials demonstrate significant improvements in:
These benefits make Contrave particularly valuable for patients with obesity-related complications including type 2 diabetes 1, 4