title: Placebo Response in Pediatric Anxiety Disorders: Results from the Child/Adolescent Anxiety Multimodal Study.
abstract: OBJECTIVE
  The aim of this study is to identify predictors of pill placebo response and to characterize the temporal course of pill placebo response in anxious youth.
  
  
  METHODS
  Data from placebo-treated patients (N = 76) in the Child/Adolescent Anxiety Multimodal Study (CAMS), a multisite, randomized controlled trial that examined the efficacy of cognitive-behavioral therapy, sertraline, their combination, and placebo for the treatment of separation, generalized, and social anxiety disorders, were evaluated. Multiple linear regression models identified features associated with placebo response and models were confirmed with leave-one-out cross-validation. The likelihood of improvement in patients receiving pill placebo-over time-relative to improvement associated with active treatment was determined using probabilistic Bayesian analyses.
  
  
  RESULTS
  Based on a categorical definition of response (Clinical Global Impressions-Improvement Scale score ≤2), nonresponders (n = 48), and pill placebo responders (n = 18) did not differ in age (p = 0.217), sex (p = 0.980), race (p = 0.743), or primary diagnosis (all ps > 0.659). In terms of change in anxiety symptoms, separation anxiety disorder and treatment expectation were associated with the degree of pill placebo response. Greater probability of placebo-related anxiety symptom improvement was observed early in the course of treatment (baseline to week 4, p < 0.0001). No significant change in the probability of placebo-related improvement was observed after week 4 (weeks 4-8, p = 0.07; weeks 8-12, p = 0.85), whereas the probability of improvement, in general, significantly increased week over week with active treatment.
  
  
  CONCLUSIONS
  Pill placebo-related improvement occurs early in the course of treatment and both clinical factors and expectation predict this improvement. Additionally, probabilistic approaches may refine our understanding and prediction of pill placebo response.
authors.affiliation: 1 Department of Psychiatry and Behavioral Neuroscience, College of Medicine, University of Cincinnati , Cincinnati, Ohio.|2 Division of Child and Adolescent Psychiatry, Department of Pediatrics, Cincinnati Children's Hospital Medical Center , Cincinnati, Ohio.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Strawn
authors.affiliation: 1 Department of Psychiatry and Behavioral Neuroscience, College of Medicine, University of Cincinnati , Cincinnati, Ohio.
authors.forename: Eric T
authors.initials: ET
authors.lastname: Dobson
authors.affiliation: 3 Carl H. Lindner College of Business, University of Cincinnati , Cincinnati, Ohio.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Mills
authors.affiliation: 3 Carl H. Lindner College of Business, University of Cincinnati , Cincinnati, Ohio.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Cornwall
authors.affiliation: 4 Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center , Pittsburgh, Pennsylvania.
authors.forename: Dara
authors.initials: D
authors.lastname: Sakolsky
authors.affiliation: 4 Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center , Pittsburgh, Pennsylvania.
authors.forename: Boris
authors.initials: B
authors.lastname: Birmaher
authors.affiliation: 5 Duke University Medical Center , Durham, North Carolina.
authors.forename: Scott N
authors.initials: SN
authors.lastname: Compton
authors.affiliation: 6 Semel Institute for Neuroscience and Human Behavior, University of California , Los Angeles (UCLA), Los Angeles, California.
authors.forename: John
authors.initials: J
authors.lastname: Piacentini
authors.affiliation: 6 Semel Institute for Neuroscience and Human Behavior, University of California , Los Angeles (UCLA), Los Angeles, California.
authors.forename: James T
authors.initials: JT
authors.lastname: McCracken
authors.affiliation: 7 University of Connecticut Health Center , West Hartford, Connecticut.
authors.forename: Golda S
authors.initials: GS
authors.lastname: Ginsburg
authors.affiliation: 8 Temple University , Philadelphia, Pennsylvania.
authors.forename: Phillip C
authors.initials: PC
authors.lastname: Kendall
authors.affiliation: 9 Weill Cornell Medical College and New York Presbyterian Hospital , New York, New York.
authors.forename: John T
authors.initials: JT
authors.lastname: Walkup
authors.affiliation: 10 Columbia University Medical Center (CUMC)/New York State Psychiatric Institute , New York, New York.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Albano
authors.affiliation: 10 Columbia University Medical Center (CUMC)/New York State Psychiatric Institute , New York, New York.
authors.forename: Moira A
authors.initials: MA
authors.lastname: Rynn
mesh_terms: D000293:Adolescent; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000523:psychology*; D001499:Bayes Theorem; D002648:Child; D015928:Cognitive Behavioral Therapy; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008297:Male; D015990:Placebo Effect; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D020280:Sertraline / Q000627:therapeutic use
chemical_list: D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline
keywords: Bayesian; antidepressant; anxiety; clinical trial; response