Meta-analysis finds no evidence for efficacy of nalmefene in treating alcohol dependence.

Current evidence from randomised controlled trials does not support the use of the opioid antagonist nalmefene for treating alcohol dependence, shows a systematic review that the authors said questioned decisions by some regulatory authorities to approve the drug for this indication. The review, published in PLoSMedicine, analysed all available randomised controlled trials evaluating nalmefene to treat alcohol dependence in adults. The researchers included five trials that met their inclusion criteria to compare the opioid antagonist with placebo, in 2567 adults with alcohol dependence. Their results showed no difference in mortality between study participants who were randomised to nalmefene and those given placebo, either after six months (risk ratio 0.39 (95% confidence interval 0.08 to 2.01) or at one year (0.98 (0.04 to 23.95))). They also found no difference in participants’ quality of life, whether in the physical component summary score of the SF-36 (mean difference 0.85 (95% confidence interval −0.32 to 2.01)) or the mental component summary score (mean difference 1.01 (−1.33 to 3.34)). Nalmefene was found to be slightly better than placebo in reducing the number of days of heavy drinking in a month. People taking the drug drank heavily for a mean of 1.65 fewer days (95% confidence interval 0.89 to 2.41 days) each month than the placebo group. Their total alcohol consumption was also slightly lower (standardised mean difference −0.20 (−0.30 to −0.10)). However, the researchers considered that their results may have been biased by the higher rate of withdrawal from studies of people taking nalmefene, with more than three times as many participants withdrawing for safety reasons at three months as in the placebo group. Sensitivity analyses showed no differences in alcohol consumption between the nalmefene and placebo groups. “This review calls into question the decisions of some of the regulatory and advisory bodies that approved nalmefene on the basis of this evidence,” wrote the researchers, led by Florian Naudet, of the INSERMCentre d’Investigation Clinique, Centre Hospitalier Universitaire de Rennes, Rennes, France. The European Medicines Agency approved nalmefene in 2012 for the treatment of alcohol dependence to help reduce alcohol consumption in men consuming more than 60 g of alcohol a day and in women consuming more than 40 g a day. And the UK National Institute for Health and Care Excellence has recommended it as a possible treatment for alcohol dependence for men who drink more than 7.5 units a day and women drinking more than five units a day. “The value of nalmefene for treatment of alcohol addiction is not established,” argued the review authors. “At best, nalmefene has limited efficacy in reducing alcohol consumption,” they concluded.