Acamprosate for alcohol dependent patients

Alcohol dependence is an important health risk factor that can lead to disability and death for people in developed and developing countries. Alcohol consumption is potentially avoidable, which emphasizes the need for effective strategies to help people who are dependent on alcohol to reduce excessive drinking and maintain abstinence following detoxification. Psychosocial programs have limited success in preventing relapse after detoxification programs. The addition of a pharmacological agent could provide support in achieving or maintaining abstinence or to cut down alcohol consumption. The synthetic glutamate antagonist acamprosate and naltrexone, which is an opioid antagonist, are used for this purpose.

This systematic review shows that acamprosate appears to be an effective and safe treatment in alcohol dependent patients for supporting continuous abstinence after detoxification from alcohol. When added to psychosocial treatment strategies, acamprosate reduced the risk of returning to any drinking after detoxification compared with treatment with a placebo (number need to treat (NNT) for one person to benefit was nine). The cumulative abstinence time was also clearly increased. Return to heavy drinking did not change. Even though the size of the treatment effect was moderate, the benefit should be valued because of the relapsing nature of alcoholism and the limited treatment options that are currently available. Diarrhea was the most frequently reported side effect with acamprosate. Overall, side effects did not cause more participants to stop treatment when taking acamprosate compared with placebo.

These conclusions are based on 24 randomised controlled trials with 6915 participants who were treated as outpatients in all but one trial that involved adolescent inpatients. The majority of participants were men, median age 42 years. Most studies were conducted in Europe; two studies were conducted in the United States and one study in each of South Korea,Australia and Brazil. The effects of acamprosate did not differ in industry-sponsored and non-profit funded trials.

Three trials compared acamprosate and naltrexone and did not indicate a superiority of one or the other drug on return to any drinking, return to heavy drinking and cumulative abstinence duration.

Authors' conclusions: 

Acamprosate appears to be an effective and safe treatment strategy for supporting continuous abstinence after detoxification in alcohol dependent patients. Even though 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.

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Background: 

Alcohol dependence is among the main leading 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 to placebo and other pharmacological agents.

Search strategy: 

We searched the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, PubMed, EMBASE and CINAHL in January 2009 and inquired manufacturers and researchers for unpublished trials.

Selection criteria: 

All double-blind randomised controlled trials (RCTs) which 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 (IPD) meta-analyses were used to verify the primary effectiveness outcomes.

Main results: 

24 RCTs with 6915 participants fulfilled the criteria of inclusion and were included in the review. Compared to placebo, acamprosate was shown to significantly reduce the risk of any drinking RR 0.86 (95% CI 0.81 to 0.91); NNT 9.09 (95% CI 6.66 to 14.28) and to significantly increase the cumulative abstinence duration MD 10.94 (95% CI 5.08 to 16.81), while secondary outcomes (gamma-glutamyltransferase, heavy drinking) did not reach statistical significance. Diarrhea was the only side effect that was more frequently reported under acamprosate than placebo RD 0.11 (95% 0.09 to 0.13); NNTB 9.09 (95% CI 7.69 to 11.11). Effects of industry-sponsored trials RR 0.88 (95% 0.80 to 0.97) did not significantly differ from those of non-profit 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 = 0.861).