A Cochrane review [Abstract] 1 included 50 studies with a total of 7793 subjects. Added to psychosocial treatment strategies, naltrexone reduced the risk of heavy drinking to 83% of the risk in the placebo group (RR 0.83, 95% CI 0.76 to 0.90; 28 trials, n=4433) and decreased drinking days by about 4% ( MD -3.89, 95% CI -5.75 to -2.04; 26 trials, n=3882). It also decreased heavy drinking days (MD - 3.25, 95% CI -5.51 to -0.99; 15 trials, n=1715), consumed amount of alcohol (MD - 10.83, 95% CI -19.69 to -1.97; 16 trials, n=1838) and gamma-glutamyltransferase (MD - 10.37, 95% CI -18.99 to -1.75; 16 trials, n=1645), while effects on return to any drinking (RR 0.96, 95 CI 0.92 to 1.00; 27 trials, n=4693) missed statistical significance. Side effects of naltrexone were mainly gastrointestinal problems e.g. nausea and sedative effects e.g. daytime sleepiness. Based on a limited study sample, effects of injectable naltrexone missed statistical significance.
A systematic review and meta-analysis 2 assessed the efficacy of acamprosate or naltrexone in reducing lapse/relapse compared to placebo in the treatment of alcohol dependence and treatment discontinuation. 22 RCTs studied acamprosate (n=5236) and 27 RCTs naltrexone (n=4199). The risk of returning to any drinking at 6 months was significantly lower for acamprosate (RR 0.83, 95% CI 0.78 to 0.89). There was little difference in the risk of participants discontinuing treatment for any reason (RR 0.91, 95% CI 0.83 to 1.00) or due to adverse events (RR 1.30, 95% CI 0.96 to 1.75) for the acamprosate compared to placebo groups. For natrexone, the risk of individuals returning to any drinking at approximately 3 months was reduced significantly (RR 0.92, 95% CI 0.86 to 1.00), as was the risk of individuals relapsing to heavy drinking at 3 months (RR 0.85, 95% CI 0.78 to 0.93). There was no significant difference between naltrexone and placebo for the risk of individuals discontinuing treatment for any reason (RR 0.94, 95% CI 0.84 to 1.05), but. risk discontinuing treatment due to adverse events was higher (RR 1.72, 95% CI 1.10 to 2.70).
A meta-analysis 3 included 122 RCTs and 1 cohort study (total 22 803 participants). The NNT to prevent return to any drinking for acamprosate was 12 (95% CI 8 to 26; risk difference [RD], -0.09; 95% CI -0.14 to -0.04; 27 studies, n = 7519) and for oral naltrexone (50 mg/d) was 20 (95% CI 11 to 500; RD, -0.05; 95% CI -0.10 to -0.002; 53 studies, n = 9140). The NNT to prevent return to heavy drinking was 12 (95% CI 8 to 26; RD -0.09; 95% CI -0.13 to -0.04) for oral naltrexone (50 mg/d). There was no statistically significant difference between acamprosate and naltrexone for return to any drinking or heavy drinking. For naltrexone and nalmefene, NNHs for withdrawal from trials due to adverse events were 48 (95% CI, 30 to 112) and 12 (95% CI, 7 to 50), respectively.
A network meta-analysis 4 exploring the comparative effectiveness of drugs used for alcohol dependence included 32 RCTs with a total of 6036 patients. Nalmefene [standardized mean difference (SMD) = -0.19, 95% confidence interval (CI) = -0.29, -0.10], baclofen (SMD = -1.00, 95% CI = -1.80, -0.19; one study) and topiramate (SMD = -0.77, 95% CI = -1.12, -0.42; I2 = 0%) showed superiority over placebo on total alcohol consumption. No efficacy was observed for naltrexone or acamprosate.
Another meta-analysis 5 assessing serious adverse effects of oral naltrexone included 98 RCTs with a total od 11 194 participants. There was no evidence of increased risk of serious adverse events for naltrexone compared to placebo (risk ratio 0.84, 95% CI 0.66-1.06).
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