title: Meta-analyses of placebo-controlled trials of acamprosate for the treatment of alcohol dependence: impact of the combined pharmacotherapies and behavior interventions study.
abstract: OBJECTIVE
  : 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.
authors.affiliation: From the Addictions Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; and Addictions Unit, McGill University Health Centre, Montreal, Canada.
authors.forename: George
authors.initials: G
authors.lastname: Dranitsaris
authors.forename: Peter
authors.initials: P
authors.lastname: Selby
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Negrete