Jeffrey R Strawn1,2, Eric T Dobson1, Jeffrey A Mills3, Gary J Cornwall3, Dara Sakolsky4, Boris Birmaher4, Scott N Compton5, John Piacentini6, James T McCracken6, Golda S Ginsburg7, Phillip C Kendall8, John T Walkup9, Anne Marie Albano10, Moira A Rynn10. 1. 1 Department of Psychiatry and Behavioral Neuroscience, College of Medicine, University of Cincinnati , Cincinnati, Ohio. 2. 2 Division of Child and Adolescent Psychiatry, Department of Pediatrics, Cincinnati Children's Hospital Medical Center , Cincinnati, Ohio. 3. 3 Carl H. Lindner College of Business, University of Cincinnati , Cincinnati, Ohio. 4. 4 Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center , Pittsburgh, Pennsylvania. 5. 5 Duke University Medical Center , Durham, North Carolina. 6. 6 Semel Institute for Neuroscience and Human Behavior, University of California , Los Angeles (UCLA), Los Angeles, California. 7. 7 University of Connecticut Health Center , West Hartford, Connecticut. 8. 8 Temple University , Philadelphia, Pennsylvania. 9. 9 Weill Cornell Medical College and New York Presbyterian Hospital , New York, New York. 10. 10 Columbia University Medical Center (CUMC)/New York State Psychiatric Institute , New York, New York.
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.
RCT Entities:
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.
Authors: Moira A Rynn; John T Walkup; Scott N Compton; Dara J Sakolsky; Joel T Sherrill; Sa Shen; Philip C Kendall; James McCracken; Anne Marie Albano; John Piacentini; Mark A Riddle; Courtney Keeton; Bruce Waslick; Allan Chrisman; Satish Iyengar; John S March; Boris Birmaher Journal: J Am Acad Child Adolesc Psychiatry Date: 2014-12-31 Impact factor: 8.829
Authors: Philip C Kendall; Scott N Compton; John T Walkup; Boris Birmaher; Anne Marie Albano; Joel Sherrill; Golda Ginsburg; Moira Rynn; James McCracken; Elizabeth Gosch; Courtney Keeton; Lindsey Bergman; Dara Sakolsky; Cindy Suveg; Satish Iyengar; John March; John Piacentini Journal: J Anxiety Disord Date: 2010-02-06
Authors: Jeffrey R Strawn; Scott N Compton; Brigitte Robertson; Anne Marie Albano; Mohamed Hamdani; Moira A Rynn Journal: J Child Adolesc Psychopharmacol Date: 2017-02-06 Impact factor: 2.576
Authors: Amy Krain Roy; Roma A Vasa; Maggie Bruck; Karin Mogg; Brendan P Bradley; Michael Sweeney; R Lindsey Bergman; Erin B McClure-Tone; Daniel S Pine Journal: J Am Acad Child Adolesc Psychiatry Date: 2008-10 Impact factor: 8.829
Authors: Scott N Compton; John T Walkup; Anne Marie Albano; John C Piacentini; Boris Birmaher; Joel T Sherrill; Golda S Ginsburg; Moira A Rynn; James T McCracken; Bruce D Waslick; Satish Iyengar; Phillip C Kendall; John S March Journal: Child Adolesc Psychiatry Ment Health Date: 2010-01-05 Impact factor: 3.033
Authors: Lesley A Norris; Lara S Rifkin; Thomas M Olino; John Piacentini; Anne Marie Albano; Boris Birmaher; Golda Ginsburg; John Walkup; Scott N Compton; Elizabeth Gosch; Philip C Kendall Journal: Child Psychiatry Hum Dev Date: 2019-12
Authors: Jeffrey R Strawn; Jeffrey A Mills; Gary J Cornwall; Sarah A Mossman; Sara T Varney; Brooks R Keeshin; Paul E Croarkin Journal: J Child Adolesc Psychopharmacol Date: 2017-08-28 Impact factor: 2.576
Authors: Jeffrey R Strawn; Scott N Compton; Brigitte Robertson; Anne Marie Albano; Mohamed Hamdani; Moira A Rynn Journal: J Child Adolesc Psychopharmacol Date: 2017-02-06 Impact factor: 2.576
Authors: Carl Y Zhang; Jennifer L Vande Voort; Deniz Yuruk; Jeffrey A Mills; Graham J Emslie; Betsy D Kennard; Taryn Mayes; Madhukar Trivedi; William V Bobo; Jeffrey R Strawn; Arjun P Athreya; Paul E Croarkin Journal: J Child Adolesc Psychopharmacol Date: 2022-06 Impact factor: 3.031
Authors: Jeffrey R Strawn; Jeffrey A Mills; Beau A Sauley; Jeffrey A Welge Journal: J Am Acad Child Adolesc Psychiatry Date: 2018-02-08 Impact factor: 8.829
Authors: Lu Lu; Hailong Li; William T Baumel; Jeffrey A Mills; Kim M Cecil; Heidi K Schroeder; Sarah A Mossman; Xiaoqi Huang; Qiyong Gong; John A Sweeney; Jeffrey R Strawn Journal: Neuropsychopharmacology Date: 2021-09-27 Impact factor: 8.294
Authors: Lu Lu; Jeffrey A Mills; Hailong Li; Heidi K Schroeder; Sarah A Mossman; Sara T Varney; Kim M Cecil; Xiaoqi Huang; Qiyong Gong; Laura B Ramsey; Melissa P DelBello; John A Sweeney; Jeffrey R Strawn Journal: J Am Acad Child Adolesc Psychiatry Date: 2021-02-04 Impact factor: 13.113