title: Long-term efficacy, tolerability and safety of nalmefene as-needed in patients with alcohol dependence: A 1-year, randomised controlled study.
abstract: This study evaluated the long-term efficacy and safety of nalmefene treatment in reducing alcohol consumption. We randomised (1:3) 675 alcohol-dependent patients ≥ 18 years of age to 52 weeks of as-needed treatment with placebo or nalmefene 18 mg/day: A total of 112 patients (68%) in the placebo group and 310 (62%) in the nalmefene group completed the study. At month 6, the co-primary outcome variables showed no statistically-significant differences between the treatment groups; but at month 13, nalmefene was more effective than placebo, both in the reduction of the number of heavy drinking days (HDDs) (- 1.6 days/month (95% CI - 2.9; - 0.3); p = 0.017) and the reduction of total alcohol consumption (TAC) (- 6.5 g/day last month (95% CI - 12.5; - 0.4); p = 0.036). In a subgroup analysis of patients with high/very high drinking risk levels at screening and at randomisation (the target population), there was a significant effect in favour of nalmefene on TAC at month 6, and on both HDD and TAC at month 13. Improvements in Clinical Global Impression and liver enzymes were greater with nalmefene, compared to placebo. Most adverse events were mild or moderate, and transient; adverse events, including those leading to dropout, were more common with nalmefene. This study provides evidence for the long-term safety and efficacy of nalmefene as-needed in alcohol-dependent patients whom continue to drink heavily, following a brief intervention.
authors.affiliation: Department of Psychiatry, University of Amsterdam, Amsterdam, The Netherlands w.vandenbrink@amc.uva.nl.
authors.forename: Wim
authors.initials: W
authors.lastname: van den Brink
authors.affiliation: H Lundbeck A/S, Valby, Denmark.
authors.forename: Per
authors.initials: P
authors.lastname: Sørensen
authors.affiliation: H Lundbeck A/S, Valby, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Torup
authors.affiliation: Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Mann
authors.affiliation: Neurosciences Institute, Hospital Clinic, Barcelona, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Gual
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 / Q000009:adverse effects / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D009292:Narcotic Antagonists; D009271:Naltrexone; C038981:nalmefene
keywords: Addiction; Clinical Global Impression; adverse effects; alcohol dependence; alcoholism; as-needed therapy; harm reduction; liver enzymes; nalmefene