What is the recommended usage and guidelines for Contrave (naltrexone and bupropion) for weight loss in adults?

Contrave for Weight Loss in Adults

Recommended Usage

Contrave (naltrexone 8mg/bupropion 90mg sustained-release) should be initiated at one tablet daily in the morning with gradual weekly escalation to the target dose of two tablets twice daily (32mg/360mg total daily), combined with lifestyle modification, in adults with BMI ≥30 kg/m² or BMI ≥27 kg/m² with weight-related comorbidities. 1, 2, 3

Dosing Protocol

Dose Escalation Schedule

• Week 1: One tablet (8mg/90mg) once daily in the morning 1, 2, 3
• Week 2: One tablet twice daily (morning and evening) 1, 2
• Week 3: Two tablets in the morning, one tablet in the evening 1, 2
• Week 4 onward: Two tablets twice daily (maximum dose: 32mg naltrexone/360mg bupropion daily) 1, 2, 3

This gradual escalation minimizes adverse effects, particularly nausea, which occurs in approximately 30% of patients but is typically mild to moderate and transient 2, 3, 4

Treatment Discontinuation Criteria

• Discontinue Contrave if the patient has not achieved at least 5% weight loss after 12 weeks at maximum dose, as continued use is unlikely to provide meaningful benefit 1, 2, 3, 5

Expected Efficacy

• Contrave produces mean weight loss of 4.8-5.0% (approximately 11-22 lbs or 5-9 kg) at 56 weeks compared to placebo 2, 3, 6
• 36-57% of patients achieve ≥5% total body weight loss, which is clinically meaningful 2, 3, 7, 4
• Weight loss with Contrave is moderate compared to phentermine/topiramate (6.7-8.9 kg) and liraglutide (5.8-5.9 kg), but allows for long-term use unlike short-term phentermine 2, 3

Mechanism of Action

• The combination works synergistically by activating pro-opiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus 1, 3
• Bupropion (dopamine/norepinephrine reuptake inhibitor) stimulates POMC neurons while naltrexone (opioid receptor antagonist) blocks opioid-mediated autoinhibition of these neurons 1, 3
• This results in reduced food cravings, decreased appetite, increased satiation, and improved control of eating behaviors 3, 6

Absolute Contraindications

Do not prescribe Contrave if any of the following are present:

• Seizure disorders or conditions predisposing to seizures (severe head trauma, CNS tumors, metabolic disorders) - bupropion significantly lowers seizure threshold 1, 2, 5
• Current or prior bulimia or anorexia nervosa - higher incidence of seizures observed 5
• Uncontrolled hypertension - both components can elevate blood pressure and heart rate 1, 2, 5
• Current opioid use (including analgesics, maintenance therapy, or partial agonists) - naltrexone blocks opioid receptors and will precipitate withdrawal in opioid-dependent individuals 2, 5
• Pregnancy or active attempts to conceive - potential teratogenic effects 2, 5
• Use of MAO inhibitors within 14 days 3

Critical Monitoring Requirements

Blood Pressure and Heart Rate

• Monitor blood pressure and heart rate periodically, especially during the first 12 weeks and dose escalation phases 2, 5
• Unlike phentermine, Contrave does not show increased cardiovascular risk and is not contraindicated in cardiovascular disease 2, 8
• Initial transient increase of approximately 1.5 mm Hg in systolic and diastolic blood pressure is followed by reduction of approximately 1 mm Hg below baseline 4

Mental Health Assessment

• Monitor patients younger than 24 years with depression closely for mood changes during the first few months due to risk of suicidal behavior and ideation 5
• Contrave was not associated with increased depression or suicidality events compared to placebo in clinical trials 7, 4

Weight Loss Efficacy

• Assess weight loss at 12 weeks - discontinue if <5% weight loss achieved 2, 3, 5

Common Adverse Effects

• Nausea (29.8%) - most common, generally mild to moderate and transient 3, 4
• Constipation, headache, vomiting, dizziness, and dry mouth 3, 4
• These effects are minimized by gradual dose escalation 2

Special Clinical Considerations

• May be particularly beneficial for patients with obesity and comorbid depression or those seeking smoking cessation or alcohol use reduction, as bupropion is the only antidepressant consistently shown to promote weight loss 3
• Treatment must be part of a comprehensive approach including dietary changes and increased physical activity 3
• Women of reproductive age must use reliable contraception 2

Switching from Other Weight Loss Medications

• When switching from phentermine to Contrave, discontinue phentermine immediately and start Contrave the next day using the standard dose escalation protocol - no washout period required 2

Cardiovascular Safety

• Available evidence does not indicate increased risk of major adverse cardiovascular events (MACE) with Contrave use 8
• For composite MACE and its components, the difference in proportions between Contrave-treated patients compared with placebo did not exceed 2.5% 8