Pharmacotherapy for Adults With Alcohol Use Disorder

Oral naltrexone (Revia), 50 mg daily, reduces alcohol consumption across multiple outcomes, and once-daily dosing offers relative ease of use. (Strength of Recommendation [SOR]: C, disease-oriented evidence.) Acamprosate and topiramate also have evidence of benefit for reducing alcohol consumption; however, acamprosate has a higher pill burden, and topiramate has a less desirable adverse effect profile. (SOR: C, disease-oriented evidence.) There is lower strength of evidence for reducing alcohol consumption when using injectable naltrexone (Vivitrol), baclofen, or gabapentin. (SOR: C, disease-oriented evidence.) Evidence remains inadequate for use of disulfiram compared with placebo for reducing alcohol consumption.¹ Current data are insufficient to understand the effect of any of the pharmacotherapies for AUD on health outcomes (e.g., mortality, quality of life, function, accidents, injury).

Practice Pointers

Excessive alcohol use is a leading cause of preventable death, contributing to more than 178,000 deaths in the United States annually per the latest data from 2020–2021.² Screening and brief intervention for unhealthy alcohol use are recommended by the U.S. Preventive Services Task Force for adults, including pregnant people.³ National surveillance data from 2022 suggest that 29.5 million people in the United States 12 years or older (10.5%) met criteria for AUD in the past year, but only 2.1% of those received medication to treat it.⁴ In 2023, the Agency for Healthcare Research and Quality published an update to their 2014 systematic review of outpatient pharmacologic treatment for AUD.¹

Medications for AUD are generally studied with psychosocial cointervention; thus, this summary reflects effects attributed to medications beyond nonpharmacologic interventions and placebo. Few studies have directly compared any of these medications. The data are limited surrounding medication effectiveness in special populations, specific to primary care, or relative to longer-term health outcomes (e.g., quality of life, accidents, injury, mortality).

Acamprosate, disulfiram, oral naltrexone, and the long-acting injectable formulation of naltrexone are approved by the U.S. Food and Drug Administration for treatment of AUD. Baclofen, gabapentin, ondansetron, prazosin, topiramate, and varenicline (Chantix) have also been studied for off-label use. Of these medications, oral naltrexone and acamprosate have the strongest and most consistent evidence and should be considered first-line treatments for AUD in primary care.

Oral naltrexone, an opioid antagonist, reduces return to heavy drinking, percentage of drinking days, and percentage of heavy-drinking days. Studies of oral naltrexone also show a nonsignificant trend toward reduction in return to any drinking. Acamprosate, an N-methyl-d-aspartate (NMDA) receptor modulator, reduces return to any drinking and percentage of total drinking days. Studies comparing naltrexone with acamprosate have not established the superiority of one medication over the other (prevent return to any drinking: oral naltrexone, number needed to treat [NNT] = 18 vs. acamprosate, NNT = 11; prevent return to heavy drinking: oral naltrexone, NNT = 11 [data not available for acamprosate]).⁵ No new comparative studies were identified since the 2014 Agency for Healthcare Research and Quality review.

Considerations when selecting acamprosate or naltrexone include dosing regimen, contraindications, and potential adverse effects (Table 1). Note that oral naltrexone is metabolized through the liver and acamprosate is metabolized by the kidneys.

Address correspondence to Alyssa Bruehlman, MD, at alyssa.bruehlman@pennmedicine.upenn.edu. Reprints are not available from the authors.

Author disclosure: No relevant financial relationships.

1.McPheeters M, O’Connor EA, Riley S, et al. Pharmacotherapy for adults with alcohol use disorder in outpatient settings: systematic review. Comparative effectiveness review no. 262. (Prepared by the RTI International–University of North Carolina at Chapel Hill Evidence-based Practice Center under contract no. 75Q80120D00007.) AHRQ publication no. 23(24)-EHC011. Agency for Healthcare Research and Quality; November 2023. https://doi.org/10.23970/AHRQEPCCER262
2.Centers for Disease Control and Prevention. Deaths from excessive alcohol use in the United States. Updated February 29, 2024. Accessed March 26, 2024. https://www.cdc.gov/alcohol/features/excessive-alcohol-deaths.html
3.Curry SJ, Krist AH, Owens DK, et al. Screening and behavioral counseling interventions to reduce unhealthy alcohol use in adolescents and adults: US Preventive Services Task Force recommendation statement. JAMA. 2018;320(18):1899-1909.
4.Substance Abuse and Mental Health Services Administration. Key substance use and mental health indicators in the United States: results from the 2022 National Survey on Drug Use and Health. November 2023. Accessed March 26, 2024. https://www.samhsa.gov/data/sites/default/files/reports/rpt42731/2022-nsduh-nnr.pdf
5.Pettinati HM, Anton RF, Willenbring ML. The COMBINE Study—an overview of the largest pharmacotherapy study to date for treating alcohol dependence. Psychiatry (Edgmont). 2006;3(10):36-39.
6.Jonas DE, Amick HR, Feltner C, et al.; Agency for Healthcare Research and Quality. Pharmacotherapy for adults with alcohol-use disorders in outpatient settings. Comparative effectiveness reviews, No. 134. Report no.: 14-EHC029-EF. May 2014. Accessed March 26, 2024. https://www.ncbi.nlm.nih.gov/books/NBK208590
7.Collins SE, Duncan MH, Saxon AJ, et al. Combining behavioral harm-reduction treatment and extended-release naltrexone for people experiencing homelessness and alcohol use disorder in the USA: a randomised clinical trial. Lancet Psychiatry. 2021;8(4):287-300.

The Agency for Healthcare Research and Quality (AHRQ) conducts the Effective Health Care Program as part of its mission to produce evidence to improve health care and to make sure the evidence is understood and used. A key clinical question based on the AHRQ Effective Health Care Program systematic review of the literature is presented, followed by an evidence-based answer based on the review. AHRQ’s summary is accompanied by an interpretation by an AFP author that will help guide clinicians in making treatment decisions.

This series is coordinated by Joanna Drowos, DO, MPH, MBA, contributing editor. A collection of Implementing AHRQ Effective Health Care Reviews published in AFP is available at https://www.aafp.org/afp/ahrq.