title: Efficacy of as-needed nalmefene in alcohol-dependent patients with at least a high drinking risk level: results from a subgroup analysis of two randomized controlled 6-month studies.
abstract: OBJECTIVE
  The aim of the study was to investigate the efficacy and safety of as-needed use of nalmefene 18 mg versus placebo in reducing alcohol consumption in patients who did not reduce their alcohol consumption after an initial assessment, i.e. the pooled subgroup of patients with at least a high drinking risk level (men: >60 g/day; women: >40 g/day) at both screening and randomization from the two randomized controlled 6-month studies ESENSE 1 (NCT00811720) and ESENSE 2 (NCT00812461).
  
  
  METHODS
  Nalmefene 18 mg and placebo were taken on an as-needed basis. All the patients also received a motivational and adherence-enhancing intervention (BRENDA). The co-primary outcomes were number of heavy drinking days (HDDs) and mean total alcohol consumption (g/day) in Month 6 measured using the Timeline Follow-back method. Additionally, data on clinical improvement, liver function and safety were collected throughout the study.
  
  
  RESULTS
  The pooled population consisted of 667 patients: placebo n = 332; nalmefene n = 335. There was a superior effect of nalmefene compared with placebo in reducing the number of HDDs [treatment difference: -3.2 days (95% CI: -4.8; -1.6); P < 0.0001] and total alcohol consumption [treatment difference: -14.3 g/day (-20.8; -7.8); P < 0.0001] at Month 6. Improvements in clinical status and liver parameters were greater in the nalmefene group compared with the placebo group. Adverse events and adverse events leading to dropout were more common with nalmefene than placebo.
  
  
  CONCLUSIONS
  As-needed nalmefene was efficacious in reducing alcohol consumption in patients with at least a high drinking risk level at both screening and randomization, and the effect in this subgroup was larger than in the total population.
authors.affiliation: Department of Psychiatry, Amsterdam Institute for Addiction Research, University of Amsterdam, Amsterdam, The Netherlands. w.vandenbrink@amc.uva.nl
authors.forename: Wim
authors.initials: W
authors.lastname: van den Brink
authors.forename: Henri-Jean
authors.initials: HJ
authors.lastname: Aubin
authors.forename: Anna
authors.initials: A
authors.lastname: Bladström
authors.forename: Lars
authors.initials: L
authors.lastname: Torup
authors.forename: Antoni
authors.initials: A
authors.lastname: Gual
authors.forename: Karl
authors.initials: K
authors.lastname: Mann
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000188:drug therapy* / Q000453:epidemiology*; D000437:Alcoholism / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D009292:Narcotic Antagonists; D009271:Naltrexone; C038981:nalmefene