Public Release: 

Meta-analysis finds evidence for nalmefene in the treatment of alcohol dependence is weak

PLOS

Currently available evidence from randomized controlled trials (RCT) does not support the use of nalmefene for harm reduction for people with alcohol dependence, according to a systematic review and meta-analysis (SRMA) published this week in PLOS Medicine. The study, conducted by Florian Naudet at INSERM, Centre Hospitalier Universitaire de Rennes, France also indicates that evidential support for the use of nalmefene to reduce alcohol consumption among this population is limited.

Nalmefene blocks the body's opioid receptors and reduces the craving for alcohol. The drug has mixed recommendations from health agencies and expert bodies for use in the treatment of alcohol dependence. Naudet and colleagues used SRMA to investigate the risks and benefits of nalmefene in the treatment of alcohol dependence in adults. The meta-analysis of five eligible RCTs (involving 2567 participants) found no differences between participants taking nalmefene versus those taking placebo in mortality after 6 months (Relative Risk = 0.39, 95% CI [0.08; 2.01]) or 1 year (RR = 0.98, 95% CI [0.04; 23.95]) of treatment, quality of life at 6 months (SF?36 physical component summary score: Mean Difference = 0.85, 95% CI [?0.32; 2.01]), or mental health (summary score MD = 1.01, 95% CI [?1.33; 3.34]). Participants taking nalmefene had fewer heavy drinking days at 6 months (MD = -1.65, 95% CI [?2.41; ?0.89]) and 1 year (MD = -1.60, 95% CI [?2.85; ?0.35]) of treatment than participants taking placebo, and their total alcohol consumption at 6 months was lower (SMD = -0.20, 95% CI [?0.30; ?0.10]). However, secondary analyses suggested these differences may have been caused in part by attrition bias.

None of the included RCTs was performed in the specific population for which nalmefene has been indicated, and none compared nalmefene with another medication such as naltrexone. A key conclusion of the SRMA is that more trials are needed. However, these findings call into question the regulatory approval of nalmefene for this purpose. The authors state, "Clinicians must be aware that the value of nalmefene for the treatment of alcohol addiction is not established. At best, nalmefene has limited efficacy in reducing alcohol consumption."

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Research Article

Funding:

Supported by a local grant from Rennes CHU (CORECT : COmité de la Recherche Clinique et Translationelle). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests:

I have read the journal's policy and the authors of this manuscript have the following competing interests: All authors have completed the Unified Competing Interest form at http://www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare that (1) No authors have support from any company for the submitted work; (2) PC was a trainee in Servier (pharmacokinetics department) for 6 months in 2013; LB, BR, RJM, BE have no relationships with any company that might have an interest in the submitted work in the previous 3 years; NF has relationships (Travel/accommodations expenses covered/reimbursed) with Servier, BMS, Lundbeck and Janssen who might have an interest in the work submitted in the previous 3 years, he was invited by Lundbeck to present an oral communication at a symposium on the neurobiology of alcohol dependence in 2014, he explicitly asked not to be paid for this presentation (and indeed was not paid); (3) No author's spouses, partners, or children have any financial relationships that could be relevant to the submitted work; and (4) none of the authors has any non-financial interests that could be relevant to the submitted work.

Citation:

Palpacuer C, Laviolle B, Boussageon R, Reymann JM, Bellissant E, Naudet F (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. PLoS Med 12(12): e1001924. doi:10.1371/journal.pmed.1001924

Author Affiliations:

INSERM Centre d'Investigation Clinique 1414, Centre Hospitalier Universitaire de Rennes, Rennes, France

Laboratoire de Pharmacologie Expérimentale et Clinique, Faculté de Médecine, Université de Rennes 1, Rennes, France

Département de Médecine Générale, Faculté de Médecine et de Pharmacie, Université de Poitiers, Poitiers, France

IN YOUR COVERAGE PLEASE USE THIS URL TO PROVIDE ACCESS TO THE FREELY AVAILABLE PAPER: http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001924

Contact:

Florian Naudet
Centre d'Investigation Clinique, CIC-P INSERM 1414
Centre Hospitalier Universitaire de Rennes et Université de Rennes 1
2 rue Henri Le Guilloux
35033 Rennes cedex 9
France
TEL : 02 99 28 43 21
floriannaudet@gmail.com

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