Cochrane for Clinicians
Putting Evidence into Practice
Effectiveness of Acamprosate in the Treatment of Alcohol Dependence
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Am Fam Physician. 2011 Mar 1;83(5):522-524.
A patient who successfully completed inpatient treatment for alcohol dependence is concerned about relapse and requests advice on measures that can help maintain abstinence from alcohol use.
Is acamprosate (Campral) effective for maintaining abstinence from alcohol use?
When used in conjunction with detoxification and psychosocial interventions for treating alcohol dependence, acamprosate can reduce the risk of any return to drinking and improve cumulative abstinence rates.1 (Strength of Recommendation = A, based on consistent, good-quality patient-oriented evidence)
Background: Alcohol dependence is among the main health risk factors in most developed and developing countries. Therapeutic success of psychosocial programs for relapse prevention is moderate, but could potentially be increased by an adjuvant treatment with the glutamate antagonist acamprosate.
Objectives: To determine the effectiveness and tolerability of acamprosate in comparison with placebo and other pharmacologic agents.
Search Strategy: The authors searched the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, PubMed, EMBASE, and CINAHL in January 2009. They also asked manufacturers and researchers about any unpublished trials.
Selection Criteria: All double-blind, randomized controlled trials that compare the effects of acamprosate with placebo or active control on drinking-related outcomes.
Data Collection and Analysis: Two authors independently extracted data. Trial quality was assessed by one author and cross-checked by a second author. Individual patient data meta-analyses were used to verify the primary effectiveness outcomes.
Main Results: Twenty-four randomized controlled trials with 6,915 participants fulfilled inclusion criteria and were considered in the review. Compared with placebo, acamprosate was shown to significantly reduce the risk of any drinking (risk ratio [RR] = 0.86; 95% confidence interval [CI], 0.81 to 0.91; number needed to treat [NNT] = 9.09; 95% CI, 6.66 to 14.28) and significantly increase the cumulative abstinence duration (mean difference = 10.94 days; 95% CI, 5.08 to 16.81), whereas secondary outcomes (e.g., γ-glutamyltransferase level, heavy drinking) did not reach statistical significance. Diarrhea was the only adverse effect that was more frequently reported for acamprosate treatment than placebo (risk difference = 0.11; 95% CI, 0.09 to 0.13; NNT = 9.09; 95% CI, 7.69 to 11.11). Effects of industry-sponsored trials (RR = 0.88; 95% CI, 0.80 to 0.97) did not significantly differ from those of nonprofit-funded trials (RR = 0.88; 95% CI, 0.81 to 0.96). In addition, the linear regression test did not indicate a significant risk of publication bias (P = .861).
Authors' Conclusions: Acamprosate appears to be an effective and safe treatment strategy for supporting continuous abstinence after detoxification in alcohol-dependent patients. Although the sizes of treatment effects appear to be rather moderate in their magnitude, they should be valued against the background of the relapsing nature of alcoholism and the limited therapeutic options currently available for its treatment.
These summaries have been derived from Cochrane reviews published in the Cochrane Database of Systematic Reviews in the Cochrane Library. Their content has, as far as possible, been checked with the authors of the original reviews, but the summaries should not be regarded as an official product of the Cochrane Collaboration; minor editing changes have been made to the text (http://www.cochrane.org).
Alcohol abuse is a major health risk worldwide, causing approximately 3 percent of deaths globally and contributing significantly to the risks of stroke, ischemic heart disease, hypertension, diabetes mellitus, and liver cancer, as well as motor vehicle collisions, drownings, and homicides.2 Although treatment of alcoholism is complex and studies of treatment effectiveness are challenging, a previous Cochrane review found that brief interventions can reduce weekly alcohol consumption, emergency department visits, and alcohol-related injuries in outpatient settings.3 Other evidence has shown that disulfiram (Antabuse) may reduce total days of drinking without improving overall abstinence,4 and naltrexone (Revia) is effective for reducing overall alcohol use.5
Acamprosate is a synthetic glutamate receptor agonist that has been prescribed in Europe for more than 20 years and was approved by the U.S. Food and Drug Administration in 2004. Although its mechanism of action remains unclear, it has been suggested that acamprosate may act to reduce processes related to alcohol withdrawal, as well as reduce the rewarding effects of alcohol intake.1
This Cochrane review evaluated the effectiveness and tolerability of acamprosate for helping patients dependent on alcohol to maintain abstinence. In all 24 of the included trials, acamprosate was prescribed for at least four weeks in addition to psychosocial interventions, which varied across studies. All trials except for one were in adult populations, and all trials except for one included pretreatment alcohol detoxification. The majority of patients included in the trials met diagnostic criteria for alcohol dependence. The typical acamprosate dosage was four to six tablets (333 mg each) per day.
Among patients taking acamprosate in the 24 trials, risk of return to any drinking was 86 percent that of patients treated with placebo (i.e., 14 percent less risk in treatment group compared with placebo). Based on statistical weighting of trials, the authors calculated a number needed to treat of 9 to prevent one additional patient from returning to drinking. Patients treated with acamprosate also maintained cumulative abstinence (i.e., total days without alcohol use, whether or not the patient had periodic return to drinking) for 11 percent longer than patients taking placebo. The only adverse effect of acamprosate that reached statistical significance compared with placebo was diarrhea (the authors calculated a weighted number needed to harm of 9), but this adverse effect did not affect adherence to treatment. Overall trial dropout because of adverse effects or any other cause was actually greater in patients taking placebo.
Three of the studies also compared acamprosate versus naltrexone; two studies compared combination treatment of acamprosate and naltrexone versus placebo; and two studies compared combination treatment of acamprosate and naltrexone versus acamprosate alone. None of these comparisons demonstrated statistically significant treatment benefits among interventions. However, these comparisons showed that acamprosate carried a higher risk of diarrhea, and that the combination of acamprosate and naltrexone led to a markedly higher rate of withdrawal because of adverse events compared with placebo or acamprosate alone.
Ten trials reported posttreatment follow-up. They found that treatment effects for return to drinking and for cumulative abstinence remained statistically significant three to 12 months after study conclusion, indicating that benefits of acamprosate may persist beyond the treatment period.
Although treatment of alcohol abuse is complicated and can be associated with high relapse rates, use of acamprosate in addition to psychosocial interventions for patients who have already been detoxified is associated with reduced return to drinking and increased cumulative abstinence during treatment and for up to one year afterward.
Address correspondence to William E. Cayley, Jr., MD, MDiv, at firstname.lastname@example.org. Reprints are not available from the author.
Author disclosure: Nothing to disclose.
1. Rösner S, Hackl-Herrwerth A, Leucht S, Lehert P, Vecchi S, Soyka M. Acamprosate for alcohol dependence. Cochrane Database Syst Rev. 2010;(9):CD004332.
2. Guilbert JJ. The world health report 2002 - reducing risks, promoting healthy life. Educ Health (Abingdon). 2003;16(2):230.
3. Kaner EF, Beyer F, Dickinson HO, et al. Effectiveness of brief alcohol interventions in primary care populations. Cochrane Database Syst Rev. 2007;(2):CD004148.
4. Fuller RK, Branchey L, Brightwell DR, et al. Disulfiram treatment of alcoholism. A Veterans Administration cooperative study. JAMA. 1986;256(11):1449–1455.
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.
The Cochrane Abstract is a summary of a review from the Cochrane Library. It is accompanied by an interpretation that will help clinicians put evidence into practice. Dr. Cayley presents a clinical scenario and question based on the Cochrane Abstract, followed by an evidence-based answer and a critique of the review. The practice recommendations in this activity are available at http://www.cochrane.org/reviews/en/ab004332.html.
The series coordinator for AFP is Kenny Lin, MD, Department of Family Medicine, Georgetown University School of Medicine, Washington, DC.
A collection of Cochrane for Clinicians published in AFP is available at http://www.aafp.org/afp/cochrane.
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