Anticonvulsants for alcohol dependence.

BACKGROUND: Alcohol dependence is a major public health problem that is characterised by recidivism and a host of medical and psychosocial complications. Besides psychosocial interventions, different pharmacological interventions have been or currently are under investigation through Cochrane systematic reviews. OBJECTIVES: The primary aim of the review is to assess the benefits/risks of anticonvulsants for the treatment of alcohol dependence. SEARCH METHODS: We searched the Cochrane Drugs and Alcohol Group Trials Register (October 2013), PubMed (1966 to October 2013), EMBASE (1974 to October 2013) and CINAHL (1982 to October 2013). SELECTION CRITERIA: Randomised controlled trials (RCTs) and controlled clinical trials (CCTs) comparing anticonvulsants alone or in association with other drugs and/or psychosocial interventions versus placebo, no treatment and other pharmacological or psychosocial interventions. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by The Cochrane Collaboration. MAIN RESULTS: A total of 25 studies were included in the review (2641 participants). Most participants were male, with an average age of 44 years. Anticonvulsants were compared with placebo (17 studies), other medications (seven studies) and no medication (two studies). The mean duration of the trials was 17 weeks (range four to 52 weeks). The studies took place in the USA, Europe, South America, India and Thailand. Variation was reported in the characteristics of the studies, including their design and the rating instruments used. For many key outcomes, the risk of bias associated with unclear or unconcealed allocation and lack of blinding affected the quality of the evidence.Anticonvulsants versus placebo: For dropouts (16 studies, 1675 participants, risk ratio (RR) 0.94, 95% confidence interval (Cl) 0.74 to 1.19, moderate-quality evidence) and continuous abstinence (eight studies, 634 participants, RR 1.21, 95% Cl 95% 0.97 to 1.52, moderate-quality evidence), results showed no evidence of differences. Moderate-quality evidence suggested that anticonvulsants reduced drinks/drinking days (11 studies, 1126 participants, mean difference (MD) -1.49, 95% Cl -2.32 to -0.65) and heavy drinking (12 studies, 1129 participants, standardised mean difference (SMD) -0.35, 95% Cl -0.51 to -0.19). Moreover, withdrawal for medical reasons (12 studies, 1410 participants, RR 1.22, 95% Cl 0.58 to 2.56, moderate-quality evidence) showed no evidence of difference, but for specific adverse effects (nine studies, 1164 participants), two of 18 adverse event outcomes favoured placebo. The direction of results was confirmed by subgroup analyses for topiramate and partially for gabapentin and valproate.Anticonvulsants versus naltrexone: No evidence of difference was shown in dropout rates (five studies, 528 participants, RR 0.74, 95% CI 0.52 to 1.06), severe relapse rates (four studies, 427 participants, RR 0.69, 95% Cl 0.44 to 1.07) and continuous abstinence rates (five studies, 528 participants, RR 1.21, 95% Cl 0.99 to 1.49); anticonvulsants were associated with fewer heavy drinking days (three studies, 308 participants, MD -5.21, 95% Cl -8.58 to -1.83), more days to severe relapse (three studies, 244 participants, MD 11.88, 95% Cl 3.29 to 20.46) and lower withdrawal for medical reasons (three studies, 245 participants, RR 0.13, 95% Cl 0.03 to 0.58). AUTHORS' CONCLUSIONS: At the current stage of research, randomised evidence supporting the clinical use of anticonvulsants to treat alcohol dependence is insufficient. Results are conditioned by heterogeneity and by the low number and quality of studies comparing anticonvulsants with other medications. The uncertainty associated with these results leaves to clinicians the need to balance possible benefits/risks of treatment with anticonvulsants versus other medications as supported by evidence of efficacy.