No High-Grade Evidence Supporting Nalmefene For Alcohol Dependency Interview with:
Dr. Florian Naudet
INSERM Centre d’Investigation Clinique 1414
Faculté de Médecine, Centre Hospitalier
Universitaire de Rennes
Laboratoire de Pharmacologie Expérimentale et Clinique
Rennes, France

Medical Research: What is the background for this study? What are the main findings?

Dr. Naudet: To reduce harm, alcohol-dependent individuals are usually advised to abstain from drinking, but controlled (moderate) drinking may also be helpful. To help people reduce their alcohol consumption, the European Medicines Agency recently approved nalmefene for use in the treatment of alcohol dependence in adults who consume more than 60 g (for men) or 40 g (for women) of alcohol per day. However, several expert bodies have concluded that nalmefene shows no benefit over naltrexone, an older treatment for alcohol dependency, and do not recommend its use for this indication.

This is problematic because randomised controlled trials (RCTs) should lead to objective conclusions concerning treatment efficacy and this was not the case concerning nalmefene’s approval.

We therefore performed a meta-analysis of aggregated data to enable an objective reappraisal of the efficacy of nalmefene for relevant health outcomes and on alcohol consumption endpoints at both 6 months (+/- 1 month) and 1 year (+/- 1 month).

We identified five RCTs that met the criteria for inclusion in our study. All five RCTs (which involved 2,567 participants) compared the effects of nalmefene with a placebo; none was undertaken in the population specified by the European Medicines Agency approval. Among the health outcomes examined in the meta-analysis, there were no differences between participants taking nalmefene and those taking placebo in mortality (death) after six months or one year of treatment, in the quality of life at six months. The RCTs included in the meta-analysis did not report other health outcomes. Participants taking nalmefene had fewer heavy drinking days per month at six months and one year of treatment than participants taking placebo, and their total alcohol consumption was lower. These differences were small in terms of clinical significance. Additionally, more people withdrew from the nalmefene groups than from the placebo groups, often for safety reasons. Thus, attrition bias cannot be excluded.

Medical Research: What should clinicians and patients take away from your report?

Dr. Naudet: These findings show that there is no high-grade evidence currently available from RCTs to support the use of nalmefene for harm reduction among people being treated for alcohol dependency. In addition, they provide little evidence to support the use of nalmefene to reduce alcohol consumption among this population. Importantly, these findings reveal a lack of information on clinically relevant outcomes in the evidence that led to nalmefene approval by the European Medicines Agency. Thus, these findings also call into question the decisions of this and other regulatory and advisory bodies that have approved nalmefene on the basis of the available evidence from RCTs.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Naudet: 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. In these studies, health outcomes should be assessed. These studies may be unrealistic from a methodological point of view because of the need for long-term follow-up and probably a large number of participants.

There is thus a need for independent and well-designed post-marketing studies.

In addition, a network meta-analysis is needed to assess the effectiveness of nalmefene in reducing alcohol consumption compared to the other active treatments available.


PLoS Med. 2015 Dec 22;12(12):e1001924. doi: 10.1371/journal.pmed.1001924. eCollection 2015.

Risks and Benefits of Nalmefene in the Treatment of Adult Alcohol Dependence: A Systematic Literature Review and Meta-Analysis of Published and Unpublished Double-Blind Randomized Controlled Trials.

Palpacuer C1, Laviolle B1,2, Boussageon R3, Reymann JM1,2, Bellissant E1,2, Naudet F1,2.

Dr. Florian Naudet (2015). No High-Grade Evidence Supporting Nalmefene For Alcohol Dependency 

Last Updated on January 2, 2016 by Marie Benz MD FAAD