Clinical question: Is there a difference in alcohol consumption between the oral and extended-release formulations of naltrexone when initiated in the hospital for patients with alcohol use disorder (AUD)?
Background: Alcohol use disorder (AUD) is common (as many as 19% of inpatients), and 94% of people with AUD do not receive medication or counseling. Despite the availability of medications for AUD (MAUD), few hospitalized patients receive them. The comparative effectiveness of initiating oral versus extended-release naltrexone in this context is not known.
Study design: Randomized clinical trial
Setting: Teaching hospital in Boston
Synopsis: Among hospitalized patients with AUD and recent heavy drinking, 248 participants were randomized to receive oral naltrexone supply on the day of discharge or extended-release injectable naltrexone. Both arms received real-world outpatient medical management with a three-month follow-up period. The majority of participants were middle-aged men, 50% self-identified as Black, and almost half had experienced recent housing insecurity. Most were insured by Medicaid. Approximately 90% had severe AUD. The study assessed as its primary outcome the three-month change in heavy drinking days (HDDs) in the preceding 30 days. The study found that both groups had a reduction in HDDs compared to baseline, with no significant difference between groups (38.4% reduction in oral naltrexone group versus 46.4% reduction in injectable naltrexone group). A limitation of the study is the lack of a third group that was referred for outpatient naltrexone initiation rather than in-hospital initiation. Nonetheless, the study’s findings are a critical addition to the evidence supporting hospital initiation of MAUD and should encourage hospital-based providers to tailor options to patients’ preferences.
Bottom line: When initiated in the hospital, both daily oral naltrexone and injectable extended-release naltrexone were similarly effective in reducing alcohol use. Patient preference, adherence with oral naltrexone, and cost should be considered when deciding between formulations.
Citation: Magane KM, 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. doi:10.1001/jamainternmed.2025.0522.
Dr. Molina is an assistant professor of medicine at Yale School of Medicine and an academic hospitalist at Yale New Haven Hospital, both in New Haven, Conn.