For a patient taking bupropion (Wellbutrin) for depression who also requires naltrexone for alcohol dependence, is taking the two drugs separately different from using the fixed‑dose combination product Contrave (bupropion‑SR plus naltrexone)?

Taking Bupropion and Naltrexone Separately vs. Contrave

For a patient taking bupropion (Wellbutrin) for depression and naltrexone for alcohol dependence, using the two medications separately is clinically different from—and strongly preferred over—using Contrave (naltrexone-bupropion ER). The separate medications allow proper dosing for each indication, whereas Contrave is FDA-approved only for obesity and uses different doses that are not appropriate for treating depression or alcohol dependence. 1

Key Differences in FDA Indications and Dosing

Contrave (Fixed-Dose Combination)

• FDA-approved exclusively for chronic weight management in adults with BMI ≥30 kg/m² or BMI ≥27 kg/m² with weight-related comorbidities 1
• Maintenance dose: 32 mg naltrexone/360 mg bupropion daily (two tablets twice daily, each containing 8 mg naltrexone/90 mg bupropion) 1
• Not FDA-approved for depression or alcohol dependence 1
• Limited evidence exists for treating major depressive disorder with this combination, with most large trials excluding patients with significant psychiatric disorders 1

Separate Medications (Wellbutrin + Naltrexone)

• Bupropion is FDA-approved for major depressive disorder at therapeutic doses of 300 mg/day (typically 150 mg twice daily for SR formulation) 2, 1
• Naltrexone is FDA-approved for alcohol dependence at 50 mg once daily 2, 1
• This approach allows proper dosing for each condition independently 2

Clinical Evidence Supporting Separate Use

Superior Outcomes with Combination Therapy

The combination of naltrexone (50 mg/day) plus an antidepressant produces significantly better outcomes than either medication alone for patients with co-occurring depression and alcohol dependence. 3

• A double-blind, placebo-controlled trial demonstrated that sertraline (200 mg/day) plus naltrexone (100 mg/day) achieved:
  • 53.7% alcohol abstinence rate vs. 21-27% with monotherapy 3
  • Median time to relapse: 98 days vs. 23-29 days with monotherapy 3
  • 83.3% of patients no longer depressed by end of treatment 3
  • Fewer serious adverse events (11.9%) compared to other treatment groups 3

Safety Profile

• Naltrexone and bupropion used separately are safe pharmacotherapeutic agents for patients with co-occurring depression and alcohol dependence 4
• The combination addresses both conditions through complementary mechanisms: bupropion works via noradrenergic/dopaminergic pathways while naltrexone blocks opioid receptors 2
• No significant pharmacokinetic interactions exist between these medications 2

Critical Safety Considerations Before Prescribing

Absolute Contraindications for Both Formulations

• Current opioid therapy: Naltrexone precipitates severe opioid withdrawal and is absolutely contraindicated 2, 1
• Uncontrolled hypertension: Bupropion can elevate blood pressure and heart rate 2, 1
• Seizure disorders or conditions lowering seizure threshold: Bupropion lowers seizure threshold (risk ~0.1% at 300 mg/day) 2
• Abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs: Increases seizure risk 2
• Current or recent MAOI use (within 14 days) 2
• Eating disorders (bulimia/anorexia): Increased seizure risk 2

Dose Adjustments Required

• Moderate to severe hepatic impairment: Maximum bupropion dose 150 mg daily 2
• Moderate to severe renal impairment (GFR <90 mL/min): Reduce bupropion dose by 50% 2
• Naltrexone requires caution in severe liver disease due to potential hepatocellular injury 2

Recommended Dosing Algorithm for Separate Medications

Bupropion for Depression

1. Start: 150 mg once daily for 3 days 2
2. Increase: 150 mg twice daily (300 mg total) if tolerated 2
3. Maximum: 400 mg/day for SR formulation, 450 mg/day for XL formulation 2
4. Timing: First dose in morning, second dose before 3 PM to minimize insomnia 2
5. Assessment: Allow 6-8 weeks at adequate dose before determining response 2

Naltrexone for Alcohol Dependence

• Standard dose: 50 mg once daily 2
• Higher doses (up to 100 mg/day) may be used based on clinical response 3

Required Monitoring Parameters

Initial and Ongoing Monitoring

• Blood pressure and heart rate: Especially during first 12 weeks, as bupropion can cause elevations 2
• Liver function tests: Baseline and regular intervals during naltrexone treatment 2
• Suicidal ideation: Particularly in patients <24 years old (bupropion carries black box warning) 2
• Seizure risk factors: Monitor for conditions that lower seizure threshold 2
• Alcohol use and craving: Regular assessment of drinking patterns 3
• Depressive symptoms: Within 1-2 weeks of initiation, then regularly 2

Clinical Advantages of Separate Medications

Flexibility in Dosing

• Allows titration of each medication independently based on therapeutic response and side effects 2
• Enables use of FDA-approved doses for each specific indication 1
• Permits continuation of one medication if the other needs to be discontinued 2

Evidence-Based Treatment

• Substance-induced depression responds better to alcohol reduction than to antidepressant therapy alone 5
• Greater reduction in drinking is associated with better depression outcomes regardless of depression type 5
• The combination addresses both conditions through complementary mechanisms without known drug interactions 2

Common Pitfalls to Avoid

Do Not Use Contrave for These Indications

• Contrave's naltrexone dose (32 mg/day at maintenance) is substantially lower than the 50-100 mg/day needed for alcohol dependence 2, 1, 3
• Contrave's bupropion dose (360 mg/day) may be inadequate or excessive depending on individual needs for depression 2, 1
• The fixed-dose combination prevents independent titration of each medication 1

Timing Considerations

• Do not start naltrexone until patient is opioid-free for at least 7-10 days to avoid precipitated withdrawal 2, 1
• Ensure blood pressure is controlled before initiating bupropion 2, 1
• Begin monitoring for treatment response early (1-2 weeks) but allow 6-8 weeks before declaring treatment failure 2

Maximum Dose Limits

• Never exceed 450 mg/day of bupropion to maintain seizure risk at 0.1% 2
• Do not combine with other medications that lower seizure threshold without extreme caution 2