What is the recommended dose of bupropion (Contrave) for weight management in patients with or without a history of seizure disorders or eating disorders?

Bupropion Dose in Contrave

Contrave contains bupropion 90 mg combined with naltrexone 8 mg per tablet, with a maintenance dose of 2 tablets twice daily (total daily dose: bupropion 360 mg/naltrexone 32 mg). 1

Titration Schedule

The American Gastroenterological Association recommends a specific 4-week titration protocol to minimize adverse effects, particularly nausea and seizure risk: 1

• Week 1: 1 tablet (8 mg naltrexone/90 mg bupropion) once daily in the morning 1
• Week 2: 1 tablet twice daily (morning and evening) 1
• Week 3: 2 tablets in the morning, 1 tablet in the evening 1
• Week 4 and beyond: 2 tablets twice daily (maintenance dose = 32 mg naltrexone/360 mg bupropion daily) 1

The second dose should not be taken late in the day to minimize insomnia risk, as bupropion has activating properties. 1

Absolute Contraindications for Contrave

Seizure disorders are an absolute contraindication because bupropion significantly lowers seizure threshold, with a seizure rate of approximately 0.1% at therapeutic doses. 2, 3 The following conditions also preclude Contrave use:

• Current or prior bulimia or anorexia nervosa due to higher seizure incidence in these populations 2, 4
• Uncontrolled hypertension, as both components elevate blood pressure and heart rate 2
• Current opioid use (including analgesics, maintenance therapy, or partial agonists), as naltrexone blocks opioid receptors 2
• Pregnancy or active attempts to conceive 2
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs due to increased seizure risk 1

Dose Adjustments for Special Populations

For moderate to severe hepatic impairment: Maximum dose is 1 tablet once daily (8 mg naltrexone/90 mg bupropion), not the full maintenance dose. 1

For moderate to severe renal impairment (GFR <90 mL/min): Reduce total daily dose by 50% due to renal clearance of bupropion metabolites. 1

Critical Monitoring Requirements

The American Heart Association recommends specific monitoring parameters: 2

• Blood pressure and heart rate: Monitor periodically throughout treatment, especially during the first 12 weeks and dose escalation phases 2
• Mental health status: Patients younger than 24 years require close monitoring for mood changes and suicidal ideation during the first few months 2
• Efficacy assessment at 12 weeks: Discontinue if less than 5% weight loss is achieved 2

Maximum Dose Considerations

The maximum dose for weight management is 32 mg naltrexone/360 mg bupropion daily (2 tablets twice daily). 1 This represents a lower bupropion dose than used for depression (300-450 mg/day) but is specifically formulated for obesity management when combined with naltrexone. 1, 5

The 300 mg/day maximum for the bupropion component in Contrave maintains seizure risk at approximately 0.1%, well within the range of other antidepressants. 3

Clinical Efficacy

Phase III trials demonstrated that naltrexone ER/bupropion ER 32/360 mg/day produced average weight loss of 11-22 lbs (5-9 kg) over 52 weeks, with significant improvements in cardiometabolic markers. 6, 5 The combination works synergistically through hypothalamic POMC neurons to reduce appetite and food cravings. 6

Common Pitfalls to Avoid

• Do not prescribe to patients with any condition predisposing to seizures beyond diagnosed epilepsy, including severe head trauma, CNS tumors, or metabolic disorders 2
• Do not use in patients requiring chronic opioid pain management, as naltrexone blocks analgesic effects 2
• Do not skip the titration schedule, as abrupt initiation at full dose significantly increases nausea and other adverse effects 1
• Do not continue beyond 12 weeks if weight loss is <5%, as this indicates non-response 2