Gamma-hydroxybutyrate (GHB) for treatment of alcohol withdrawal and prevention of relapses

Background Chronic excessive alcohol consumption may lead to dependence, and to alcohol withdrawal syndrome (AWS) in case of abrupt drinking cessation. Gamma‐hydroxybutyric acid (GHB) can prevent and suppress withdrawal symptoms, and improve the medium‐term abstinence rate. However, clear estimates of its beneficial and harmful effects have not been yet established. Objectives To evaluate the efficacy and safety of GHB for the treatment of AWS and the prevention of relapse. Search methods We searched the Cochrane Drugs and Alcohol Group's Register of Trials (October 2008), PubMed, EMBASE, CINAHL (January 2005 to October 2008), EconLIT (1969 to February 2008), and reference lists of retrieved articles. Selection criteria Randomized controlled trials (RCT) and Controlled Prospective Studies (CPS) evaluating the efficacy and the safety of GHB versus placebo or other pharmacological treatments. Data collection and analysis Three authors independently extracted data and assessed the methodological quality of the studies. Main results Thirteen RCTs were included, 11 of which had been conducted in Italy. For alcohol withdrawal syndrome, comparing GHB 50mg versus placebo, results from 1 study (23 participants) favour GHB for withdrawal symptoms: MD ‐12.1 (95% CI ‐15.9 to ‐8.29), but tolerated side effects were more frequent in the GHB group: RR 16.2 (95% CI 1.04 to 254.9; based on 7 of 11 patients in the GHB group developing transitory vertigo compared to none in the placebo group). In the comparison of GHB 50mg versus Clomethiazole, results from 1 study (21 participants) favour GHB for withdrawal symptoms: MD ‐3.40 (95% CI ‐5.09 to ‐1.71). For GHB 100mg versus Clomethiazole, results from 1 study (98 participants) favour Clomethiazole for side effects: RR 1.84 (95% CI 1.19 to 2.85). At mid‐term, comparing GHB 50mg/day with placebo, 1 study (71 participants, 3 months follow‐up) favour GHB for abstinence rate (RR 5.35, 95% CI 1.28 to 22.4), controlled drinking (RR 2.13, 95% CI 1.07 to 5.54), relapses (RR 0.36, 95% CI 0.21 to 0.63), and number of daily drinks (MD ‐4.60, 95% CI ‐6.18 to ‐3.02). On abstinence, GHB performed better than Naltrexone (NTX) (2 studies, 64 participants) (RR 2.59, 95% CI 1.35 to 4.98 at 3 months) and than Disulfiram (1 study, 59 participants) (RR 1.66, 95% CI 0.99 to 2.80 at 12 months, slightly significant). The combination of GHB and NTX was better than NTX for abstinence (RR 12.3, 95% CI 1.79 to 83.9 at 3 months; 1 study, 35 participants). The combination of NTX, GHB and Escitalopram was better than Escitalopram alone for abstinence (RR 2.02 95% CI 1.03 to 3.94 at 3 months; RR 4.58, 95% CI 1.28 to 16.5 at 6 months; 1 study, 23 participants). For Alcohol Craving Scale, results favour GHB over placebo (MD ‐4.50, 95% CI ‐5.81 to ‐3.19 at 3 months; 1 study, 71 participants) and over Disulfiram at 12 months (MD ‐1.40, 95% CI ‐1.86 to ‐0.94, from 1 study with 41 participants). All other comparisons and outcomes did not show significant differences. Authors' conclusions There is insufficient randomised evidence to be confident of a difference between GHB and placebo, or to determine reliably if GHB is more or less effective than other drugs for the treatment of alcohol withdrawl or the prevention of relapses. The small amount of randomised evidence available suggests that GHB 50mg may be more effective than placebo in the treatment of AWS, and in preventing relapses and craving in previously detoxified alcoholics during the first 3 months of follow‐up. This review does not provide evidence in favour or against GHB compared to benzodiazepines and Clomethiazole for treatment of AWS; but, again based on a small amount of randomised evidence, GHB appears better than NTX and Disulfiram in maintaining abstinence and preventing craving in the medium term (3 to 12 months). The review does not provide evidence of a difference in side effects between GHB and benzodiazepines, NTX or Disulfiram. These findings should be considered alongside concerns that have been raised about GHB regarding the risk of developing addiction, and the misuse or abuse of the drug, suggesting to use GHB only under strict medical surveillance.