Clinical question: Is there a difference in effectiveness between oral and injectable naltrexone at discharge for alcohol use disorder (AUD)?
Background: AUD is common among inpatients, and most do not receive medication or counseling at discharge, leading to high rates of post-hospitalization acute care utilization. Naltrexone has been shown to increase the likelihood of decreased alcohol intake and/or sobriety and is available as both a daily oral tablet and a monthly intramuscular (IM) injection. While the injection is more expensive, theoretically, increased compliance might make it more cost-effective.
Study design: Open-label, randomized, controlled trial in a single, urban, academic hospital in the U.S.
Synopsis: Over a 4-year period, hospitalized patients with AUD were randomized to daily oral naltrexone or monthly extended-release IM naltrexone prior to discharge. Patients also had monthly follow-up with a study nurse after hospitalization to address medication management. Self-reported heavy drinking days (HDD) in the 90 days post-hospitalization (the primary outcome), decreased in both groups. There was no significant difference between oral (38.4% fewer HDD) and IM (46.4% fewer HDD) naltrexone. The mean Short Inventory of Problems Revision 2 score (an assessment of problems related to alcohol use) also improved in both groups, without a significant difference between groups. Medication adherence was poor overall, with high adherence in only 27% of patients in the oral group and 41% in the IM group. Median healthcare costs were lower ($1,630 versus $5,208) in the oral naltrexone group. There was no difference in reported alcohol-related healthcare utilization between the groups.
Bottom line: Oral and IM naltrexone are similarly efficacious in terms of reducing self-reported HDD and alcohol-related problems for the treatment of patients with AUD at hospital discharge. IM naltrexone is associated with higher adherence and cost.
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. Sehgal is the division chief of hospital medicine at the South Texas Veterans Affairs Healthcare System and an associate clinical professor at UT Health San Antonio in San Antonio.