Should Naltrexone Be Discontinued in Patients Who Continue Heavy Drinking?
No, naltrexone should not be discontinued in patients who continue heavy drinking—in fact, naltrexone is specifically designed to reduce heavy alcohol consumption and can be safely continued even in actively drinking patients, including those with compensated cirrhosis. 1, 2
Naltrexone Works During Active Drinking
- Naltrexone's mechanism of action specifically targets ongoing alcohol consumption by blocking opioid receptors, reducing both craving and the euphoric effects of alcohol. 3, 4
- The extended-release injectable formulation (380 mg monthly) has been proven safe in 624 actively drinking alcohol-dependent patients over 6 months, with no increase in liver enzyme elevations compared to placebo. 1
- Patients who were drinking heavily throughout clinical trials showed no increase in hepatic adverse events when receiving naltrexone at recommended doses. 1
- Recent evidence demonstrates that naltrexone reduces relapse rates from 54-60% to 23-31% when combined with psychosocial treatment, with a modest but clinically meaningful effect size of 0.15-0.2. 4
Critical Safety Distinction: Liver Disease Type Matters
The key is distinguishing between different types of liver disease:
- Naltrexone is contraindicated in acute hepatitis, decompensated cirrhosis, and active alcoholic hepatitis. 4, 5
- However, compensated cirrhosis is NOT an absolute contraindication—recent high-quality evidence shows naltrexone is safe in patients with severe alcohol-associated cirrhosis. 6, 2
- The historical concern about hepatotoxicity only occurred at doses much higher than the standard 50 mg daily dose used for alcohol dependence. 3
When to Actually Stop Naltrexone
Discontinue naltrexone only if:
- The patient develops acute hepatitis or decompensated cirrhosis (new ascites, encephalopathy, variceal bleeding). 4
- Liver function tests show significant elevation (>3x upper limit of normal) that is new and attributable to naltrexone rather than ongoing alcohol consumption. 4
- The patient requires opioid medications, as naltrexone will block their analgesic effects. 3
Monitoring Strategy for Continued Use
- Obtain baseline liver function tests before initiating naltrexone. 4
- Monitor liver enzymes every 3-6 months during treatment, or monthly in patients with compensated cirrhosis. 4
- Gamma-glutamyltransferase (GGT) levels actually decreased in patients receiving naltrexone 380 mg compared to placebo, suggesting potential benefit rather than harm. 1
Alternative Medications Only for Specific Contraindications
If naltrexone is truly contraindicated due to decompensated cirrhosis or active hepatitis:
- Switch to baclofen (10 mg three times daily), which is the only alcohol pharmacotherapy proven safe in randomized trials among cirrhotic patients. 4
- Consider acamprosate (666 mg three times daily), which has no hepatic metabolism and carries zero hepatotoxicity risk. 4, 7
- Both alternatives require the patient to be abstinent for 3-7 days after last alcohol consumption before initiation. 4, 7
Common Pitfall to Avoid
The most dangerous error is discontinuing effective naltrexone therapy based on outdated hepatotoxicity concerns from the 1990s. 2 This deprives patients of evidence-based treatment that can prevent progression of liver disease by reducing alcohol consumption. Hospitalization for alcohol-related complications is actually an ideal time to continue or initiate naltrexone, not to stop it. 2