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Most Effective Meds for Alcohol Use Disorder Flagged


In conjunction with psychosocial interventions, oral naltrexone and acamprosate are both effective first-line drug therapies for alcohol use disorder (AUD), results of a systematic review and meta-analysis found.


  • Researchers evaluated efficacy and comparative efficacy of three therapies for AUD that are approved in the United States (acamprosate, naltrexone, and disulfiram) and six that are commonly used off-label (baclofen, gabapentin, varenicline, topiramate, prazosin, and ondansetron).

  • Data came from 118 randomized clinical trials lasting at least 12 weeks with 20,976 participants.

  • 74% of these studies included psychosocial co-interventions, and the primary outcome was alcohol consumption.

  • Numbers needed to treat (NNT) were calculated for medications with at least moderate strength of evidence for benefit.


  • Acamprosate (NNT = 11) and naltrexone (50 mg/d; NNT = 18) had the highest strength of evidence and were both associated with statistically significant improvement in drinking outcomes.

  • Oral naltrexone but not acamprosate was also associated with lower rates of return to heavy drinking (NNT = 11) compared with placebo.

  • Injectable naltrexone was not associated with return to any or heavy drinking but was associated with fewer drinking days over the 30-day treatment period (weighted mean difference, -4.99 days).

  • The four trials that directly compared acamprosate with oral naltrexone did not consistently establish superiority of either medication for alcohol use outcomes, and among off-label drugs, only topiramate had moderate strength of evidence for benefit.


“Alcohol use disorder affects more than 28.3 million people in the United States and is associated with increased rates of morbidity and mortality. In conjunction with psychosocial interventions, these findings support the use of oral naltrexone, 50 mg/d, and acamprosate as first-line pharmacotherapies for alcohol use disorder,” the authors write.


The study, with first author Melissa McPheeters, PhD, MPH, RTI International, Research Triangle Park, North Carolina, was published online November 7, 2023 in JAMA.


Most study participants had moderate to severe AUD, and the applicability of the findings to people with mild AUD is uncertain. The mean age of participants was typically between ages 40 and 49 years, and it’s unclear whether the medications have similar efficacy for older or younger age groups. Information on adverse effects was limited.


Funding for the study was provided by the Agency for Healthcare Research and Quality of the US Department of Health and Human Services. The authors have disclosed no relevant conflicts of interest.

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