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Meta-Analyses of Placebo-Controlled Trials of Acamprosate for the Treatment of Alcohol Dependence: Impact of the Combined Pharmacotherapies and Behavior Interventions Study

Dranitsaris, George MPharm; Selby, Peter MD; Negrete, Juan Carlos MD

Journal of Addiction Medicine: June 2009 - Volume 3 - Issue 2 - p 74-82
doi: 10.1097/ADM.0b013e318182d890
Original Article

Objectives: The Combined Pharmacotherapies and Behavior Interventions Study (COMBINE) reported no significant difference between acamprosate and placebo in the treatment of alcohol dependence. To evaluate the impact of COMBINE, we performed a meta-analysis of acamprosate placebo-controlled trials with the inclusion of data from COMBINE. As a secondary analysis, we added the COMBINE data to a recently published meta-analysis of naltrexone placebo-controlled trials.

Methods: A structured literature search of major databases was performed from January 1990 to August 2007 for acamprosate placebo-controlled randomized trials. Mean differences in cumulative abstinent days (CAD) and abstinence rates (AR) from eligible studies were statistically combined to calculate point estimates and 95% CI for differences in CAD and AR.

Results: Ten and 16 studies evaluating CAD and AR, respectively were suitable for statistical pooling. The findings revealed that acamprosate was superior to placebo in the mean number of CAD (P < 0.001) and AR (pooled AR = 1.58; P < 0.001). The pooled AR for naltrexone was also significant indicating a relative benefit over placebo (AR = 1.27; P < 0.001). The COMBINE trial results contributed a weight of less than 15% to the final pooled statistical outcomes for both agents.

Conclusions: The current study confirmed that acamprosate and naltrexone are both effective agents for the treatment of patients with alcohol dependence. Systematic reviews with meta-analyses of randomized controlled trials and randomized controlled trials with adequate sample sizes are in the same (highest) level of evidence. Therefore, clinicians should use both these sources of information as their foundation for selecting optimal therapy for patients with alcohol dependence.

From the Addictions Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; and Addictions Unit, McGill University Health Centre, Montreal, Canada.

Received for publication December 28, 2007; accepted May 27, 2008.

Send correspondence and reprint requests to George Dranitsaris, Statistical Consultant, 283 Danforth Avenue, Suite 448, Toronto, Canada M4K 1N2. E-mail:

Supported by Prempharm Inc., the Canadian distributor of acamprosate. The corresponding author had full access to the data in the study, conducted the analysis and had the final responsibility for the decision to submit the article. George Dranitsaris received support from Prempharm Inc. to perform the analysis. All of the co-authors participated in a medical advisory board meeting hosted by the sponsor.

© 2009 American Society of Addiction Medicine