Can a patient currently taking Wellbutrin (bupropion) for depression safely start naltrexone for alcohol dependence?

Combining Wellbutrin and Naltrexone: Safety and Recommendations

Yes, a patient can safely take Wellbutrin (bupropion) for depression and start naltrexone for alcohol dependence—this combination is not only safe but may actually be more effective than either medication alone. 1, 2

Evidence Supporting the Combination

The combination of an antidepressant with naltrexone has demonstrated superior outcomes compared to monotherapy in patients with co-occurring depression and alcohol dependence:

• A double-blind, placebo-controlled trial showed that combining sertraline (an SSRI) with naltrexone produced a 53.7% alcohol abstinence rate, compared to only 21.3% with naltrexone alone, 27.5% with sertraline alone, and 23.1% with placebo. 2

• The combination therapy also delayed relapse to heavy drinking significantly longer (median 98 days) compared to naltrexone alone (29 days), sertraline alone (23 days), or placebo (26 days). 2

• Importantly, the medication combination group reported fewer serious adverse events (11.9%) compared to other treatment groups (25.9% overall). 2

Why This Combination Works

Bupropion and naltrexone work through complementary mechanisms without pharmacokinetic interactions that would preclude their use together. 1, 3

• Naltrexone blocks opioid receptors, reducing alcohol craving and the pleasurable "high" associated with drinking. 4, 5

• Bupropion works through noradrenergic and dopaminergic pathways to treat depression, and may also help with alcohol-related issues. 3

• The FDA has actually approved a combination product (naltrexone-bupropion ER) for obesity management, demonstrating the safety of using these medications together. 1

Critical Safety Screening Required

Before starting naltrexone in a patient on bupropion, verify the following absolute contraindications:

For Naltrexone:

• The patient must NOT be taking any opioid medications, as naltrexone will precipitate severe opioid withdrawal. 1, 3
• Naltrexone can cause hepatocellular injury, though this occurs primarily at dosages much higher than the 50 mg/day recommended for alcohol dependence. 1, 4, 5
• Check baseline liver function tests, as naltrexone should be used cautiously in patients with severe liver disease. 6

For Bupropion (already on board):

• Confirm no history of seizure disorders, as bupropion lowers seizure threshold. 3
• Verify blood pressure is controlled, as bupropion can elevate blood pressure and heart rate. 1, 3
• Ensure the patient is not abruptly discontinuing alcohol, benzodiazepines, or antiepileptic drugs, as this increases seizure risk with bupropion. 3

Dosing Recommendations

Naltrexone:

• Start naltrexone at 50 mg once daily, which is the standard dose for alcohol dependence. 6, 4, 5
• Naltrexone should only be used as an adjunct to comprehensive treatment including psychosocial interventions like Alcoholics Anonymous or professional counseling programs. 6, 4

Bupropion (continue current regimen):

• Typical therapeutic dose for depression is 300 mg/day (150 mg twice daily for SR formulation or 300 mg once daily for XL). 3
• Maximum dose should not exceed 450 mg/day to maintain seizure risk at 0.1%. 3

Monitoring Parameters

Monitor the following parameters after starting naltrexone:

• Blood pressure and heart rate periodically, especially in the first 12 weeks, as bupropion can cause elevations. 1, 3
• Liver function tests at baseline and periodically during naltrexone treatment. 1
• Depressive symptoms and suicidal ideation, particularly in patients under 24 years old. 1, 3
• Alcohol use patterns and abstinence rates. 2
• Common side effects of naltrexone include nausea and vomiting, which are typically mild. 5

Important Clinical Considerations

One case report documented worsening depression when naltrexone was used in a patient with combined alcohol and opioid dependence, though this resolved when naltrexone was discontinued. 7 However, this appears to be rare, and the larger controlled trial showed that combination therapy with an antidepressant actually improved depression outcomes. 2

Naltrexone and acamprosate are considered first-line pharmacological treatments for alcohol dependence, with naltrexone recommended for patients aiming to reduce alcohol intake who do not have severe liver disease. 1, 6

The combination of bupropion with naltrexone may be particularly beneficial for patients with comorbid depression and alcohol dependence, as it addresses both conditions through complementary mechanisms while maintaining a favorable safety profile. 1, 2