What is the efficacy of Contrave (bupropion-naltrexone) for weight loss?

Effectiveness of Contrave for Weight Loss

Contrave (naltrexone/bupropion) provides moderate weight loss of approximately 2.0-4.1 kg (4.4-9.0 lbs) with 36-57% of patients achieving at least 5% weight loss from baseline. 1

Mechanism of Action

• Contrave combines naltrexone (an opioid receptor antagonist) and bupropion (a dopamine/norepinephrine reuptake inhibitor) in a sustained-release formulation 1
• The combination works synergistically by activating pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus 1
• Bupropion stimulates POMC neurons while naltrexone blocks the opioid-mediated autoinhibition of these neurons, reducing food cravings and improving control of eating behaviors 1

Clinical Efficacy

• In four Phase III clinical trials (COR-I, COR-II, COR-BMOD, COR-DM), Contrave demonstrated statistically significant and clinically meaningful weight loss compared to placebo 2
• Average weight loss across these studies was approximately 5-9 kg (11-22 lbs) from baseline 2
• When compared to placebo, the additional weight loss attributable to Contrave is approximately 4.5% of total body weight 3
• In the COR-I trial specifically, participants taking naltrexone 32 mg/bupropion 360 mg daily achieved 6.1% weight loss compared to 1.3% with placebo 4
• About 48% of patients taking the full dose of Contrave (naltrexone 32 mg/bupropion 360 mg) achieved at least 5% weight loss compared to only 16% of those on placebo 4

Dosing and Administration

• Contrave tablets contain 8 mg naltrexone and 90 mg bupropion in a sustained-release formulation 1
• Initial prescription should be for 1 tablet daily, with a gradual increase by 1 tablet per week 1
• Maximum recommended dose is 2 tablets twice daily (total daily dose: naltrexone 32 mg/bupropion 360 mg) 1
• Treatment should be discontinued if a patient has not achieved at least 5% weight loss after 12 weeks at the maximum dose 1

Side Effects and Safety Considerations

• Most common adverse effects include nausea (29.8%), constipation, headache, vomiting, dizziness, and dry mouth 1, 4
• Neuropsychiatric effects may occur, including seizures, cognitive impairment, anxiety, sleep disorders, and psychotic symptoms 5
• Contrave may increase blood pressure and cause cardiac arrhythmias in some patients 5
• Contraindicated in patients with uncontrolled hypertension, seizure disorders, eating disorders, and during or within 14 days of taking MAO inhibitors 1
• Not recommended for patients with a history of depression or suicidal ideation 5

Comparison to Other Weight Loss Medications

• Contrave produces modest weight loss similar to other FDA-approved anti-obesity medications 6
• Weight loss with Contrave (2.0-4.1 kg) is less than that seen with phentermine/topiramate (6.7-8.9 kg) and liraglutide (5.8-5.9 kg) 1
• In systematic reviews, phentermine-topiramate was associated with greater weight loss compared to naltrexone-bupropion 1
• Lorcaserin and Contrave yielded similar weight loss but have different adverse effect profiles 6

Special Considerations

• May be particularly beneficial for patients with obesity and comorbid depression or those seeking smoking cessation or alcohol use reduction 1
• Bupropion is the only antidepressant consistently shown to promote weight loss 1
• Multiple drug interactions are possible due to the pharmacokinetic and pharmacodynamic properties of both components 5
• Treatment should be part of a comprehensive approach that includes dietary changes and increased physical activity 1