Implementing AHRQ Effective Health Care Reviews
Helping Clinicians Make Better Treatment Choices
Pharmacotherapy for Adults with Alcohol Use Disorder
Am Fam Physician. 2016 Jul 15;94(2):155-157.
Author disclosure: No relevant financial affiliations.
Key Clinical Issue
What are the potential benefits and adverse effects of medications used to treat alcohol use disorder (AUD) in adult outpatients?
The oral medications acamprosate, naltrexone, and disulfiram, and the long-acting injectable formulation of naltrexone have been approved by the U.S. Food and Drug Administration for AUD. Acamprosate and oral naltrexone improve alcohol consumption outcomes for patients with AUD. (Strength of recommendation [SOR]: C, based on disease-oriented evidence.) However, studies directly comparing these medications have not consistently established the superiority of one medication over another.
Evidence related to injectable naltrexone is currently limited. Evidence from well-controlled trials of disulfiram suggests that treatment with disulfiram does not result in an overall reduction in alcohol consumption. (SOR: C, based on disease-oriented evidence.) Evidence is insufficient to permit conclusions about the effect of acamprosate or naltrexone on health outcomes (e.g., mortality, quality of life, function, accidents).
Primary care physicians commonly encounter adults with AUD. In 2013, the prevalence of AUD among adults in the United States was 7%,1 and alcohol misuse is the third leading cause of preventable death in the United States, after tobacco use and obesity.2 The U.S. Preventive Services Task Force recommends that physicians routinely screen adults for alcohol misuse and provide brief behavioral counseling interventions to reduce alcohol misuse.3 Alcohol use was previously subcategorized as harmful use, alcohol abuse, and alcohol dependence; however, the Diagnostic and Statistical Manual of Mental Disorders, 5th ed., outlines criteria for a single diagnosis of AUD that is measured from mild to severe depending on symptoms.4
Of the medications approved by the U.S. Food and Drug Administration for AUD, there is moderate evidence that acamprosate and oral naltrexone reduce alcohol consumption outcomes. A meta-analysis comparing acamprosate and oral naltrexone did not find a statistically significant difference between the two drugs with regard to return to any drinking5–8 or return to heavy drinking.5–7 Most studies included a psychosocial intervention in addition to the medication.
Clinical Bottom Line: Efficacy and Effectiveness of Medications for Alcohol Use Disorder
Acamprosate (vs. placebo)
Reduced the risk of return to any drinking: RD = −0.09 (95% CI, −0.14 to −0.04), NNT = 12 ● ● ○
Had similar effect on return to heavy drinking: RD = −0.01 (95% CI, −0.04 to 0.03) ● ● ○
Reduced the percentage of drinking days: WMD = −8.8 (95% CI, −12.8 to −4.8) ● ● ○
Disulfiram (vs. placebo) did not have a significant effect on return to any drinking: RD = −0.04 (95% Cl, −0.11 to 0.03) ● ○ ○
Naltrexone, 50 mg orally (vs. placebo)
Reduced the risk of return to any drinking: RD = −0.05 (95% CI, −0.10 to −0.00), NNT = 20 ● ● ○
Reduced the risk of return to heavy drinking: RD = −0.09 (95% CI, −0.13 to 0.04), NNT = 12 ● ● ○
Reduced the percentage of drinking days: WMD = −5.4 (95% CI, −7.5 to −3.2) ● ● ○
Reduced the percentage of heavy drinking days: WMD = −4.1 (95% CI, −7.6 to −0.61) ● ● ○
Naltrexone injection (vs. placebo)
Had similar effect on return to any drinking: RD = −0.04 (95% CI, −0.10 to 0.03) ● ○ ○
Had similar effect on return to heavy drinking: RD = −0.01 (95% CI, −0.14 to 0.13) ● ○ ○
Reduced the percentage of heavy drinking days: WMD = −4.6 (95% CI, −8.5 to −0.56) ● ○ ○
Topiramate* (vs. placebo)
Reduced the percentage of drinking days: WMD = −8.5 (95% CI, −15.9 to −1.1) ● ● ○
Reduced the percentage of heavy drinking days: WMD = −11.5 (95% CI, −18.3 to −4.8) ● ● ○
Reduced the number of drinks per drinking day: WMD = −1.1 (95% CI, −1.7 to −0.4) ● ● ○
The evidence is insufficient to determine the efficacy of other drugs, including amitriptyline, aripiprazole, atomoxetine, baclofen, buspirone, citalopram, desipramine, fluoxetine, fluvoxamine, gabapentin, imipramine, olanzapine, ondansetron, paroxetine, quetiapine, varenicline, and viloxazine.
Acamprosate vs. naltrexone
No significant difference between the two medications in return to any drinking ● ● ○
No significant difference between the two medications in return to heavy drinking ● ● ○
No significant difference between the two medications in the percentage of drinking days● ○ ○
note: Studies typically included psychosocial cointerventions, and effect sizes reflect the added benefits of medications beyond those of psychosocial cointerventions. Alcohol use disorder is defined as meeting criteria in the Diagnostic and Statistical Manual of Mental Disorders, 5th ed.
CI = confidence interval; NNT = number needed to treat; RD
REFERENCESshow all references
1. National Institute on Alcohol Abuse and Alcoholism. Alcohol facts and statistics. http://www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/alcohol-facts-and-statistics. Accessed March 5, 2016....
2. Mokdad AH, Marks JS, Stroup DF, Gerberding JL. Actual causes of death in the United States, 2000. JAMA. 2004;291(10):1238–1245.
3. Moyer VA. Screening and behavioral counseling interventions in primary care to reduce alcohol misuse: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2013;159(3):210–218.
4. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, Va.: American Psychiatric Association; 2013.
5. Anton RF, O'Malley SS, Ciraulo DA, et al.; COMBINE Study Research Group. Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. JAMA. 2006;295(17):2003–2017.
6. Kiefer F, Jahn H, Tarnaske T, et al. Comparing and combining naltrexone and acamprosate in relapse prevention of alcoholism: a double-blind, placebo-controlled study. Arch Gen Psychiatry. 2003;60(1):92–99.
7. Morley KC, Teesson M, Reid SC, et al. Naltrexone versus acamprosate in the treatment of alcohol dependence: a multi-centre, randomized, double-blind, placebo-controlled trial. Addiction. 2006;101(10):1451–1462.
8. Mann K, Lemenager T, Hoffmann S, et al.; PREDICT Study Team. Results of a double-blind, placebo-controlled pharmacotherapy trial in alcoholism conducted in Germany and comparison with the US COMBINE study. Addict Biol. 2013;18(6):937–946.
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 upon the review. AHRQ's summary is accompanied by an interpretation by an AFP author that will help guide clinicians in making treatment decisions. For the full review, clinician summary, and consumer summary, go to https://www.effectivehealthcare.ahrq.gov/ehc/index.cfm/search-for-guides-reviews-and-reports/?pageAction=displayProduct&productID=2161.
This series is coordinated by Kenny Lin, MD, MPH, Associate Deputy Editor for AFP Online.
A collection of Implementing AHRQ Effective Health Care Reviews published in AFP is available at http://www.aafp.org/afp/ahrq.
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