What is the recommended dose of Naltrexone (opioid receptor antagonist) for treating alcohol dependence?

Recommended Naltrexone Dosage for Alcohol Dependence

The recommended dose of naltrexone for treating alcohol dependence is 50 mg once daily orally, or alternatively as a 380 mg monthly intramuscular injection. 1, 2, 3

Oral Naltrexone Dosing

• The standard oral dosing regimen is 50 mg once daily, which was used in the placebo-controlled studies that demonstrated naltrexone's efficacy as an adjunctive treatment for alcoholism for up to 12 weeks 3
• Alternative oral dosing schedules include 100 mg on Mondays and Wednesdays, and 150 mg on Fridays for patients who may benefit from supervised administration 2, 3
• For patients initiating treatment, especially those with concerns about hepatotoxicity, starting with 25 mg daily and then increasing to 50 mg daily if well tolerated is a reasonable approach 3

Injectable Naltrexone Dosing

• Extended-release injectable naltrexone (Vivitrol) is administered as a 380 mg intramuscular injection once monthly 1, 2
• The injectable formulation may improve medication adherence compared to daily oral dosing 2

Mechanism of Action and Efficacy

• Naltrexone functions as a competitive antagonist at mu opioid receptors, blocking the euphoric effects of alcohol and reducing cravings 2
• Meta-analyses have shown that naltrexone is effective in reducing relapse to heavy drinking with an effect size in the 0.15 to 0.2 range 4
• The number needed to treat to prevent return to any drinking is estimated to be approximately 20 for naltrexone 1

Important Clinical Considerations

• Patients must be opioid-free before starting naltrexone to avoid precipitating withdrawal 3
• Naltrexone undergoes hepatic metabolism and has potential hepatotoxicity concerns, though this is uncommon at the standard 50 mg dose 1, 4
• Liver function tests should be performed at baseline and every 3-6 months due to potential hepatotoxicity at supratherapeutic doses 2
• The most common side effects include nausea and vomiting 5
• Naltrexone should be used as part of a comprehensive treatment program that includes psychosocial support 6

Special Populations and Precautions

• Naltrexone has not been specifically studied in patients with alcoholic hepatitis or alcoholic cirrhosis 1
• For patients with liver disease, acamprosate may be a safer alternative as it has no hepatic metabolism 1
• Naltrexone cannot be used in patients requiring opioid medications for pain control 2
• For surgical patients on naltrexone, oral formulations should be held for 2-3 days prior to elective procedures if opioids are expected 2
• Extended-release naltrexone should be held for 24-30 days after the last injection before elective procedures 2

Treatment Duration

• The optimal duration of treatment has not been well established, though many clinical trials used a 12-week treatment period 3, 4
• Some clinicians recommend one year of treatment for sustained benefit 4

Combination Therapy

• Some studies suggest that combining naltrexone with other medications such as gabapentin (up to 1,200 mg/day) during the first 6 weeks of treatment may improve outcomes, particularly for patients with poor sleep or history of alcohol withdrawal 7