VIENNA – , results of the first randomized controlled trial (RCT) show.
After 3 months, 64% of patients who received naltrexone were abstinent from alcohol, compared with 22% of patients who received placebo, Manasa Alla, MD, a hepatologist from the Institute of Liver and Biliary Sciences (ILBS), New Delhi, said at the European Association for the Study of the Liver (EASL) 2023, where she presented the study findings.
Importantly, naltrexone was found to be safe for patients with compensated cirrhosis. “This fragile population of patients has limited drugs to help them quit alcohol. Naltrexone can be a valuable addition to their measures to reduce craving and on their journey to reach de-addiction and abstinence,” Dr. Alla said.
Hepatotoxicity with naltrexone is rare and data are limited. The Food and Drug Administration previously placed a warning on its use for patients with alcoholic liver disease and underlying cirrhosis.
As a clinician constantly challenged with treating patients with AUD and cirrhosis, Dr. Alla wanted to explore the safety of naltrexone and to test its suitability for these patients who struggle to quit alcohol.
“Here we aimed to primarily test the safety of naltrexone in achieving abstinence and reducing alcohol cravings in patients with alcohol-related cirrhosis,” she said, adding, “The FDA black box warning has been removed, but it has never been tested in an RCT in patients with cirrhosis, so this is exactly what we did here.
“Naltrexone is a very good anti-alcohol-craving drug. If we can establish its safety in cirrhotic patients, it may have very good potential in reducing AUD and reducing the related complications of continued alcohol intake,” Dr. Alla said.
Safety, abstinence, lapse, and relapse assessed
The prospective, double-blind, single-center study at the ILBS in New Delhi, enrolled 100 patients with alcohol dependence and cirrhosis between 2020 and 2022. Participants were randomly assigned in a 1:1 ratio to receive naltrexone (50 mg/d) or placebo for 12 weeks. All participants attended regular counseling sessions with the resident psychiatrist. At baseline, the biochemical and drinking-related assessment scores between active and placebo groups of patients with compensated cirrhosis were matched.
Abstinence from alcohol was assessed through self-reported mean number of standard drinks (12 g alcohol per day). Findings were corroborated through an interview with a family member. Serum ethyl glucuronide levels were measured in cases of discrepancy. A relapse was considered to be consumption of over four standard alcoholic drinks/month; a lapse was considered any other alcohol drinking event not classified as relapse.
The primary outcome was the proportion of patients who achieved and maintained alcohol abstinence at 12 weeks; secondary outcomes were the proportion of patients who took naltrexone without a liver-related adverse effect compared with placebo at 12 weeks, the number of relapses and lapses, the difference in craving scores on the Obsessive Compulsive Drinking Scale (OCDS) between groups at 4, 8, and 12 weeks and at 6 months and 12 months, and the proportion of patients who achieved and maintained alcohol abstinence at 6 months.
