Naltrexone
Deborah Russell-Brown
Naltrexone has been a successful treatmeant for alcohol use disorder and other related disorders for a long time. However, its popularity has come against a backdrop of lingering questions: Is extended-release injectable naltrexone or daily oral naltrexone more effective? To what extent does initiating naltrexone at hospital discharge for patients suffering from the effects of heavy drinking factor into their recovery and future use?
According to results of the Alcohol Disorder Hospital Treatment (ADOPT) study, published in the June 2025 issue of JAMA Internal Medicine, both formulations, the injectable and oral pill, appear effective.
“Both forms of naltrexone were found to be clinically effective, neither superior to the other in reducing alcohol use or preventing acute health care utilization when initiated at hospital discharge,” said corresponding author Jeffrey Samet, MD, from Boston Medical Center. “We were looking for a potential difference, thinking one would be more efficacious, but in truth, drinking reduction rates were remarkably similar in both groups.”
In addition, researchers found that initiating naltrexone at hospital discharge did indeed reduce heavy drinking days post-discharge.
ADOPT, a randomized clinical trial conducted at Boston University’s teaching hospital, ran between 2016 and 2020. Researchers looked at 248 adults hospitalized with alcohol use disorder and recent heavy drinking episodes, defined as five or more drinks for men and four or more drinks for women. Participants were randomly assigned to receive either daily oral naltrexone or a one-time extended-release I.M. injection on the discharge day, with follow-up doses and support provided post-discharge. This included structured addiction-focused medical management with a trained nurse and follow-up counseling visits.
The oral naltrexone arm began treatment with a 25 mg dose for 3 days, increasing to 50 mg daily. Those who tolerated the medication, but didn’t reach treatment goals, could be escalated to 100 mg. The injectable naltrexone group received a 380 mg gluteal injection on the discharge day followed by two additional injections at 1-month intervals. Both groups were encouraged to attend monthly follow-up visits with the study nurse to support medication adherence.
No clear winner
Data showed both forms of naltrexone reduced the percentage of heavy drinking days over the 30 days preceding the 3-month follow up. Patients in the oral group reported a decrease from 66.7% to 27.4% in heavy drinking days, while those in the injectable group reported a reduction from 70.7% to 23.8%. Although the injectable arm showed a slightly greater reduction in heavy drinking days, the difference was not statistically significant.
Adherence rates were higher in the injectable group—40.7% met high adherence criteria compared to 26.6% in the oral group—suggesting an advantage in medication delivery that bypasses daily pill-taking. Likewise, there were no significant differences between groups regarding hospital readmissions or emergency department visits at 3 months.
Both formulations were well-tolerated and treatment-related serious adverse events were rare. Two patients in the injectable naltrexone group experienced significant reactions—a suicide attempt and an injection site abscess. Four events occurred in the oral naltrexone group, including alcohol withdrawal and a UTI.
Clinical implications, future directions
“Where the two formulations appear similarly effective, factors like a patient’s treatment preference, access to follow-up care, and housing stability may be especially important for clinicians to take into account—and they may also be valuable areas for future research,” said study author Kara Magane from Boston University School of Public Health.
Ultimately, she said, the goal is to make alcohol use disorder treatment both routine and patient-centered in inpatient settings.
“Hospitalization is a ‘reachable moment’ when patients can make the connection between their drinking and their medical problem and then consider an effective approach to treatment including the use of a medication,” said Samet. ■