Placebo Response in Pediatric Anxiety Disorders

Results from the Child/Adolescent Anxiety Multimodal Study

Jeffrey R. Strawn*, Eric T. Dobson, Jeffrey A. Mills, Gary J. Cornwall, Dara Sakolsky, Boris Birmaher, Scott N. Compton, John Piacentini, James T. McCracken, Golda S. Ginsburg, Phillip C. Kendall, John T. Walkup, Anne Marie Albano, Moira A. Rynn

*Corresponding author for this work

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Objectives: 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.

Original languageEnglish (US)
Pages (from-to)501-508
Number of pages8
JournalJournal of Child and Adolescent Psychopharmacology
Volume27
Issue number6
DOIs
StatePublished - Aug 1 2017

Fingerprint

Anxiety Disorders
Anxiety
Placebos
Pediatrics
Separation Anxiety
Linear Models
Therapeutics
Sertraline
Bayes Theorem
Cognitive Therapy
Randomized Controlled Trials

Keywords

  • Bayesian
  • antidepressant
  • anxiety
  • clinical trial
  • response

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

Strawn, J. R., Dobson, E. T., Mills, J. A., Cornwall, G. J., Sakolsky, D., Birmaher, B., ... Rynn, M. A. (2017). Placebo Response in Pediatric Anxiety Disorders: Results from the Child/Adolescent Anxiety Multimodal Study. Journal of Child and Adolescent Psychopharmacology, 27(6), 501-508. https://doi.org/10.1089/cap.2016.0198
Strawn, Jeffrey R. ; Dobson, Eric T. ; Mills, Jeffrey A. ; Cornwall, Gary J. ; Sakolsky, Dara ; Birmaher, Boris ; Compton, Scott N. ; Piacentini, John ; McCracken, James T. ; Ginsburg, Golda S. ; Kendall, Phillip C. ; Walkup, John T. ; Albano, Anne Marie ; Rynn, Moira A. / Placebo Response in Pediatric Anxiety Disorders : Results from the Child/Adolescent Anxiety Multimodal Study. In: Journal of Child and Adolescent Psychopharmacology. 2017 ; Vol. 27, No. 6. pp. 501-508.
@article{a89d03b5eb8943619177d530789b47c2,
title = "Placebo Response in Pediatric Anxiety Disorders: Results from the Child/Adolescent Anxiety Multimodal Study",
abstract = "Objectives: 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.",
keywords = "Bayesian, antidepressant, anxiety, clinical trial, response",
author = "Strawn, {Jeffrey R.} and Dobson, {Eric T.} and Mills, {Jeffrey A.} and Cornwall, {Gary J.} and Dara Sakolsky and Boris Birmaher and Compton, {Scott N.} and John Piacentini and McCracken, {James T.} and Ginsburg, {Golda S.} and Kendall, {Phillip C.} and Walkup, {John T.} and Albano, {Anne Marie} and Rynn, {Moira A.}",
year = "2017",
month = "8",
day = "1",
doi = "10.1089/cap.2016.0198",
language = "English (US)",
volume = "27",
pages = "501--508",
journal = "Journal of Child and Adolescent Psychopharmacology",
issn = "1044-5463",
publisher = "Mary Ann Liebert Inc.",
number = "6",

}

Strawn, JR, Dobson, ET, Mills, JA, Cornwall, GJ, Sakolsky, D, Birmaher, B, Compton, SN, Piacentini, J, McCracken, JT, Ginsburg, GS, Kendall, PC, Walkup, JT, Albano, AM & Rynn, MA 2017, 'Placebo Response in Pediatric Anxiety Disorders: Results from the Child/Adolescent Anxiety Multimodal Study', Journal of Child and Adolescent Psychopharmacology, vol. 27, no. 6, pp. 501-508. https://doi.org/10.1089/cap.2016.0198

Placebo Response in Pediatric Anxiety Disorders : Results from the Child/Adolescent Anxiety Multimodal Study. / Strawn, Jeffrey R.; Dobson, Eric T.; Mills, Jeffrey A.; Cornwall, Gary J.; Sakolsky, Dara; Birmaher, Boris; Compton, Scott N.; Piacentini, John; McCracken, James T.; Ginsburg, Golda S.; Kendall, Phillip C.; Walkup, John T.; Albano, Anne Marie; Rynn, Moira A.

In: Journal of Child and Adolescent Psychopharmacology, Vol. 27, No. 6, 01.08.2017, p. 501-508.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Placebo Response in Pediatric Anxiety Disorders

T2 - Results from the Child/Adolescent Anxiety Multimodal Study

AU - Strawn, Jeffrey R.

AU - Dobson, Eric T.

AU - Mills, Jeffrey A.

AU - Cornwall, Gary J.

AU - Sakolsky, Dara

AU - Birmaher, Boris

AU - Compton, Scott N.

AU - Piacentini, John

AU - McCracken, James T.

AU - Ginsburg, Golda S.

AU - Kendall, Phillip C.

AU - Walkup, John T.

AU - Albano, Anne Marie

AU - Rynn, Moira A.

PY - 2017/8/1

Y1 - 2017/8/1

N2 - Objectives: 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.

AB - Objectives: 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.

KW - Bayesian

KW - antidepressant

KW - anxiety

KW - clinical trial

KW - response

UR - http://www.scopus.com/inward/record.url?scp=85027850628&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85027850628&partnerID=8YFLogxK

U2 - 10.1089/cap.2016.0198

DO - 10.1089/cap.2016.0198

M3 - Article

VL - 27

SP - 501

EP - 508

JO - Journal of Child and Adolescent Psychopharmacology

JF - Journal of Child and Adolescent Psychopharmacology

SN - 1044-5463

IS - 6

ER -