title: A randomised, double-blind, placebo-controlled, efficacy study of nalmefene, as-needed use, in patients with alcohol dependence.
abstract: This study evaluated the efficacy of as-needed use of the opioid system modulator nalmefene in reducing alcohol consumption in patients with alcohol dependence. Seven hundred and eighteen patients (placebo=360; nalmefene=358), ≥ 18 years of age, with a diagnosis of alcohol dependence, ≥ 6 heavy drinking days and an average alcohol consumption ≥ WHO medium drinking risk level in the 4 weeks preceding screening, were randomised (1:1) to 24 weeks of as-needed placebo or nalmefene 18 mg/day. The co- primary efficacy analyses showed a significantly superior effect of nalmefene compared to placebo in the change from baseline to month 6 in heavy drinking days (group difference: -1.7 days/month [95% CI -3.1; -0.4]; p=0.012) and a better but not significant effect in reducing total alcohol consumption (group difference: -5.0 g/day last month [95% CI -10.6; 0.7]; p=0.088). A subgroup analysis showed that patients who did not reduce their drinking prior to randomisation benefitted more from nalmefene. Improvements in Clinical Global Impression and reductions in liver enzymes were greater in the nalmefene group than in the placebo group. Adverse events were more common with nalmefene; the incidence of adverse events leading to dropout was similar in both groups. This study provides evidence for the efficacy of nalmefene, which constitutes a new pharmacological treatment paradigm in terms of treatment goal (reduced drinking) and dosing regimen (as-needed), in alcohol dependent patients unable to reduce alcohol consumption on their own.
authors.affiliation: Neurosciences Institute, Hospital Clinic, Barcelona, Spain. Electronic address: tgual@clinic.ub.es.
authors.forename: Antoni
authors.initials: A
authors.lastname: Gual
authors.forename: Yuan
authors.initials: Y
authors.lastname: He
authors.forename: Lars
authors.initials: L
authors.lastname: Torup
authors.forename: Wim
authors.initials: W
authors.lastname: van den Brink
authors.forename: Karl
authors.initials: K
authors.lastname: Mann
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000188:drug therapy*; D000437:Alcoholism / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D009292:Narcotic Antagonists; D009271:Naltrexone; C038981:nalmefene
keywords: Alcohol dependence; As-needed; Harm-reduction; Nalmefene; Opioid antagonist; Treatment