Both Oral and Extended-release Injectable Naltrexone Effective for Alcohol Use Disorder When Initiated at Hospital Discharge

Patients with alcohol use disorder (AUD) are frequently hospitalized, but the vast majority do not receive medication for AUD (MAUD) at discharge. Starting MAUD in the hospital can help to address this treatment gap. Naltrexone is an effective treatment for AUD, but there are no trials comparing the oral and long-acting injectable (LAI) formulations among patients being discharged from general medical hospitals. In this open-label, randomized clinical trial conducted at an urban academic hospital in Massachusetts, 2016–2020, investigators compared oral with LAI naltrexone administered on discharge to hospitalized patients with AUD. The primary outcome was percentage of heavy drinking days (HDD) in the last 30 days at three-month follow up, assessed via self-report and alcohol biomarkers derived from blood specimens.

• Of 248 patients randomized, 217 (88 percent) completed the three-month follow up; 199 patients were male, the mean age was 49 years, and 116 were unhoused (i.e., ≥1 night in the last three months).
• At three-month follow-up, there was a significant decline in percentage of HDD from baseline among patients receiving oral (-38 percent) and LAI naltrexone (-46 percent); the difference between the two formulations was not significant.
• The difference in odds of hospitalization or ED visit over the three months for oral versus LAI naltrexone was not significant.

Comments: This study confirmed that naltrexone decreases HDD, and that initiating naltrexone on hospital discharge is feasible and effective. The similar efficacy of the oral and LEI naltrexone formulations emphasizes the importance of tailoring medication recommendations to patient preference, availability, cost, and post-discharge follow-up logistics.

Elliott Brady, MD, MPH* & Darius A. Rastegar, MD

* 2024–2025 Rich Saitz Editorial Intern & Addiction Medicine Fellow, Montefiore Einstein Addiction Medicine Fellowship Program

Reference: Magane KM, Dukes KA, Fielman S, et al. Oral vs extended-release injectable naltrexone for hospitalized patients with alcohol use disorder: a randomized clinical trial. JAMA Intern Med. 2025; 185(6):635–645.