REVIEW OF: Magane KM et al, JAMA Internal Medicine 2025;e250522

STUDY TYPE: Open-label RCT

Naltrexone is a first-line treatment for alcohol use disorder (AUD), but it is typically initiated only after discharge, and its use during hospitalization remains limited. This delay increases the risk that patients will be lost to follow-up after leaving the hospital. No head-to-head studies had compared oral versus extended-release intramuscular (IM) naltrexone initiated at discharge in patients hospitalized for AUD.

The Alcohol Disorder Hospital Treatment (ADOPT) study addressed this gap. Conducted at a single urban academic hospital, it enrolled 248 inpatients with AUD randomly assigned to flexibly dosed oral naltrexone or 380 mg IM naltrexone monthly, with medications provided directly rather than by outside pharmacy. The injectable group received their first injection before discharge; the oral group received medications on discharge day. The primary outcome was percentage of heavy drinking days at three-month follow-up.

Both groups experienced substantial reductions in heavy drinking: from 66.7% to 27.4% in the oral group and from 70.7% to 23.8% in the IM group. Although the injectable group showed a slightly greater reduction, the difference was not statistically significant. Acute healthcare utilization, the secondary outcome, was also similar: 54.1% in the oral group vs 61.1% in the IM group. Both formulations were well tolerated, with no serious adverse events reported.

These findings suggest that either formulation is a safe and effective choice for initiating AUD treatment during hospitalization. The IM formulation may improve adherence but carries higher cost and limited availability. Oral naltrexone remains a cost-effective and accessible option for most patients.

This study was unblinded, had a relatively short follow-up, and lacked a control group. Larger, multisite studies with longer follow-up are needed to confirm these findings and establish long-term benefits.

CARLAT TAKE
Hospitalization offers a crucial opportunity to initiate effective AUD treatment. Both oral and injectable naltrexone initiated at discharge significantly reduce heavy drinking days, with no meaningful difference in clinical outcomes at three months. Don’t delay—starting naltrexone before discharge provides clinical benefit and reduces the risk of losing patients to follow-up.