Researchers question value of nalmefene for treating alcohol dependency

The value of nalmefene for reducing alcohol consumption in patients who are alcohol-dependent has been questioned by the authors of a systematic review and meta-analysis published in PLoS Medicine^[1]
on 22 December 2015.

“Clinicians must be aware that the value of nalmefene for the treatment of alcohol addiction is not established,” say the researchers, led by Florian Naudet from the Faculty of Medicine at the University of Rennes, France. “At best, nalmefene has limited efficacy in reducing alcohol consumption.”

Researchers based the conclusions of their main study on the results of five randomised controlled trials (RCTs) involving 2,567 patients. Four additional RCTs involving 353 participants were also considered as part of a sensitivity analysis.

The results of the five RCTs revealed that there was no difference in mortality after six months of treatment between patients taking nalmefene and those taking a placebo (relative risk [RR] 0.39, 95% confidence interval [CI] 0.08 to 2.01) or after one year (RR 0.98, 95% CI 0.04 to 23.95).

There was also no difference in quality of life or mental health scores at six months (mean difference [MD] 0.85, 95% CI -0.32 to 2.01 and MD 1.01, 95% CI -1.33 to 3.34, respectively).

Patients taking nalmefene did, however, have fewer heavy drinking days at six months (MD -1.65, 95% CI -2.41 to -0.89) and after a year (MD -1.60, 95% CI -2.85 to -0.35) compared with those taking the placebo. The total alcohol consumption in the nalmefene group at six months was also lower.

Nalmefene, an opioid antagonist, has been approved in Europe for the treatment of alcohol dependence in male adults who consume more than 60g of alcohol per day or more than 40g per day in female adults since December 2012.

The RCTs included in the research were not performed in the specific population for which nalmefene has been indicated, and none compared nalmefene with another medication, such as fellow opioid antagonist naltrexone.

The researchers conclude that, compared with placebo, there was “no evidence for the efficacy of nalmefene on health outcomes”.

“This review calls into question the decisions of some of the regulatory and advisory bodies that have approved nalmefene,” say the researchers. “Given our results, certain conditions should be set by health authorities for the maintenance of nalmefene market approval. In our opinion, RCTs against placebo and naltrexone proving the superiority of nalmefene in the approved indication are needed.”

European countries have been divided about making nalmefene available. In the UK, the National Institute for Health and Care Excellence (NICE) recommends it as a “possible” treatment for alcohol dependence but the NICE evidence review group distanced itself from its earlier advice in August 2015^[2]
.

The French National Authority for Health Transparency Committee is also cautious about the drug, saying it provides only a minor improvement in actual benefit compared with psychosocial support alone in the treatment of alcohol dependence. Nalmefene has not been recommended for reimbursement by the Swedish authorities because it is thought to be no better than alternative products – a similar view reached by the Institute for Quality and Efficiency in Health Care in Germany.

Manufacturer Lundbeck, which markets nalmefene as Selincro, says “robust scientific data” underpins the decision by NICE to recommend the drug. “Alcohol dependence is estimated to affect 14 million people in Europe.” says a spokesperson for Lundbeck. “According to the World Health Organization, more than 90% of the patients are not treated and only few treatment options are available. Nalmefene has demonstrated a positive efficacy and safety profile for heavy drinkers and is recommended by NICE to help people reduce their dependence on alcohol.”