title: The declining efficacy of naltrexone pharmacotherapy for alcohol use disorders over time: a multivariate meta-analysis.
abstract: BACKGROUND
  Oral naltrexone is an FDA-approved medication for treating alcohol use disorders. Although its efficacy has been supported in multiple clinical trials, an earlier review found that its effect sizes (ESs) on relapse to heavy drinking and, to a lesser extent, percent days drinking were smaller in more recent trials and in multicenter than in single-site studies. We examined whether these findings held when studies from 2004 to 2009 were taken into account, and whether single-site versus multicenter trials, the use of placebo run-in periods, and placebo group improvement accounted for variation in naltrexone effects and decreasing effects over time.
  
  
  METHODS
  A multivariate meta-analysis of naltrexone pharmacotherapy trials for alcohol use disorders was conducted. All analyses simultaneously modeled ESs on outcomes of percent days abstinent and relapse to heavy drinking. Potential moderators of medication effects that were examined included publication year, multicenter design (vs. single site), placebo run-in period, and placebo group improvement.
  
  
  RESULTS
  Statistically significant between-group differences on percent days abstinent (the inverse of percent days drinking) and relapse to heavy drinking favored naltrexone over placebo. Year of publication was a significant moderator for both outcomes, with more recent trials having smaller ESs. Neither multi- versus single-site study, the interaction between multi- versus single-site study and year of publication, nor placebo run-in period was a significant moderator of naltrexone effects. Although placebo group improvement was modestly associated with smaller between-group naltrexone versus placebo ESs, only 21 studies provided usable information on placebo group improvement. Within those studies, there was no relationship between naltrexone ESs and time, so placebo group improvement was not examined as a moderator of that relationship.
  
  
  CONCLUSIONS
  Naltrexone ESs have attenuated over time. Moderators that explain why effects have been decreasing remain to be determined.
authors: HSR&D Center for Health Care Evaluation, VA Palo Alto Health Care System, Stanford University Medical School, Menlo Park, CA 94025, USA. acdelre@stanford.edu
authors: A C
authors: AC
authors: Del Re
authors: Natalya
authors: N
authors: Maisel
authors: Janet
authors: J
authors: Blodgett
authors: John
authors: J
authors: Finney
mesh_terms: D000437:Alcoholism / Q000188:drug therapy*; D006801:Humans; D015999:Multivariate Analysis; D009271:Naltrexone / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D009292:Narcotic Antagonists; D009271:Naltrexone
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