Can I prescribe naltrexone and gabapentin to a 44-year-old patient with a heavy history of drug and alcohol use who is currently taking venlafaxine and trazodone?

Can You Prescribe Naltrexone and Gabapentin Together?

Yes, you can prescribe naltrexone and gabapentin together for this patient, but only if there is no evidence of alcoholic liver disease or significant hepatic impairment—naltrexone is absolutely contraindicated in any degree of alcoholic liver disease. 1

Critical First Step: Assess Liver Function

Before prescribing naltrexone, you must rule out alcoholic liver disease through:

• Liver function tests (AST, ALT, bilirubin, INR) 2, 1
• Clinical assessment for cirrhosis (ascites, spider angiomata, hepatomegaly) 2
• Imaging if clinically indicated 3

If any hepatic impairment exists, do not prescribe naltrexone—use acamprosate instead as it carries zero hepatotoxicity risk. 2, 1

Safety Profile of the Combination

Naltrexone Considerations

• Naltrexone is contraindicated in alcoholic liver disease due to hepatotoxicity concerns 2, 1
• In patients without liver disease, naltrexone reduces heavy drinking days and is FDA-approved for alcohol use disorder 4, 5
• The combination of naltrexone with gabapentin has been studied and shows improved outcomes during early abstinence (first 6 weeks) 6

Gabapentin Considerations

• Gabapentin combined with alcohol markedly increases risk of falls, fractures, altered mental status, and cardiovascular effects, especially at doses ≥600 mg/day 7
• The FDA label notes gabapentin has abuse potential, particularly in patients with history of polysubstance abuse 8
• Your patient's heavy drug and alcohol history places them at higher risk for gabapentin misuse 8
• Gabapentin shows promise for reducing heavy drinking days, though evidence is less consistent than for naltrexone 4, 5

Drug Interaction Concerns

• Venlafaxine has documented dependence potential in patients with substance use history 9
• Trazodone adds additional CNS depression when combined with gabapentin 7
• The combination of gabapentin, trazodone, and ongoing alcohol use creates synergistic sedative effects 7

Recommended Treatment Algorithm

If Liver Function is Normal:

1. Start naltrexone 50 mg daily 6, 4
2. Add gabapentin up to 1,200 mg/day for the first 6 weeks only 6
3. Discontinue gabapentin after 6 weeks as benefits do not persist beyond this period 6
4. Continue naltrexone long-term 4, 5

If Any Liver Disease is Present:

1. Do not prescribe naltrexone under any circumstances 2, 1
2. Prescribe acamprosate instead: 666 mg three times daily (1,998 mg/day) for patients ≥60 kg 2
3. Avoid gabapentin due to lack of robust evidence and safety concerns with alcohol co-administration 7

Critical Monitoring Requirements

Given this patient's polysubstance history, implement intensive monitoring:

• Weekly visits during first 6 weeks to assess for gabapentin dose escalation or drug-seeking behavior 8
• Urine drug screens to monitor for concurrent substance use 3
• Assess for signs of gabapentin misuse: tolerance development, self-dose escalation, using gabapentin to relieve withdrawal from other substances 8
• Monitor for falls, altered mental status, and sedation given the CNS depressant load (gabapentin + trazodone + potential alcohol use) 7
• Counsel explicitly on avoiding alcohol during gabapentin therapy due to synergistic sedation and fall risk 7

Common Pitfalls to Avoid

• Never prescribe naltrexone without first confirming normal liver function 1
• Do not continue gabapentin beyond 6 weeks as efficacy data only supports short-term use in combination therapy 6
• Do not underestimate gabapentin's abuse potential in this high-risk patient with polysubstance history 8
• Do not prescribe gabapentin without explicit counseling about alcohol avoidance 7
• Ensure the patient is already abstinent or detoxified before starting naltrexone 4

Psychosocial Integration

Pharmacotherapy alone is insufficient—integrate evidence-based behavioral interventions:

• Cognitive behavioral therapy (CBT) 1
• Motivational enhancement therapy (MET) 1
• Medical management visits 6

The COMBINE study (n=917) demonstrated that combined behavioral intervention with pharmacotherapy produces optimal outcomes 1.