Gamma-hydroxybutyrate for treatment of alcohol withdrawal and prevention of relapses: a Cochrane review

Background: Gamma-hydroxybutyric acid (GHB) is used to prevent and treat alcohol withdrawal syndrome (AWS), and improve the mid-term abstinence rate. Objective: To evaluate the efficacy and safety of GHB. Methods: We searched Cochrane Register of Trials, PubMed, EMBASE, CINAHL, EconLIT. Three authors independently extracted data and assessed quality of studies. Results: Thirteen Randomized Clinical Trials were included (11 in Italy); six (286 participants) evaluated AWS and seven (362) mid-term. One study vs. placebo favours GHB 50mg/Kg/day for withdrawal symptoms: WMD -12.1 (95% CI, -15.9 to -8.29) and placebo for side effects (RR 16.2; 1.04-254.9). GHB was better than Chlormethiazole only for 4-points withdrawal scale, whereas side effects were not different. At mid-term, GHB was better than placebo for abstinence rate (RR 5.35; 1.28-22.4), controlled drinking (RR 2.13; 1.07-5.54), relapses (RR 0.36; 0.21-0.63), number of daily drinks (WMD -4.60; -6.18 to -3.02), and craving (WMD: -4.50; -5.81 to -3.19). GHB performed better than Naltrexone and Disulfiram on abstinence (RR 2.59; 1.35-4.98/1.66; 0.99-2.80), and better than Disulfiram for craving (WMD -1.40; -1.86 to-0.94). In all the other comparisons the differences were not statistically significant. Conclusions: GHB is effective compared to placebo for the treatment of AWS and for mid-term abstinence. GHB is not better than benzodiazepines and Chlormethiazole for AWS, but it is better than Naltrexone and Disulfiram in some measures of mid-term efficacy. Side effects of GHB are not statistically different from those with other drugs. However, concern has been raised regarding the risk of developing addiction, misuse or abuse.