title: Placebo group improvement in trials of pharmacotherapies for alcohol use disorders: a multivariate meta-analysis examining change over time.
abstract: OBJECTIVE
  Placebo group improvement in pharmacotherapy trials has been increasing over time across several pharmacological treatment areas. However, it is unknown to what degree increasing improvement has occurred in pharmacotherapy trials for alcohol use disorders or what factors may account for placebo group improvement. This meta-analysis of 47 alcohol pharmacotherapy trials evaluated (1) the magnitude of placebo group improvement, (2) the extent to which placebo group improvement has been increasing over time, and (3) several potential moderators that might account for variation in placebo group improvement.
  
  
  METHODS
  Random-effects univariate and multivariate analyses were conducted that examined the magnitude of placebo group improvement in the 47 studies and several potential moderators of improvement: (a) publication year, (b) country in which the study was conducted, (c) outcome data source/type, (d) number of placebo administrations, (e) overall severity of study participants, and (f) additional psychosocial treatment.
  
  
  RESULTS
  Substantial placebo group improvement was found overall and improvement was larger in more recent studies. Greater improvement was found on moderately subjective outcomes, with more frequent administrations of the placebo, and in studies with greater participant severity of illness. However, even after controlling for these moderators, placebo group improvement remained significant, as did placebo group improvement over time.
  
  
  CONCLUSIONS
  Similar to previous pharmacotherapy placebo research, substantial pretest to posttest placebo group improvement has occurred in alcohol pharmacotherapy trials, an effect that has been increasing over time. However, several plausible moderator variables were not able to explain why placebo group improvement has been increasing over time.
authors.affiliation: Center for Health Care Evaluation, Stanford University Medical School, VA Palo Alto Health Care System, 152MPD, 795 Willow Rd, Menlo Park, CA 94025, USA. acdelre@stanford.edu
authors.forename: A C
authors.initials: AC
authors.lastname: Del Re
authors.forename: Natalya
authors.initials: N
authors.lastname: Maisel
authors.forename: Janet C
authors.initials: JC
authors.lastname: Blodgett
authors.forename: Paula
authors.initials: P
authors.lastname: Wilbourne
authors.forename: John W
authors.initials: JW
authors.lastname: Finney
mesh_terms: D019973:Alcohol-Related Disorders / Q000175:diagnosis / Q000188:drug therapy*; D018849:Controlled Clinical Trials as Topic / Q000379:methods / Q000639:trends*; D006801:Humans; D015999:Multivariate Analysis; D015990:Placebo Effect; D012107:Research Design / Q000639:trends*; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome