@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.}",
note = "Funding Information: Dr. Strawn receives support from the National Institute of Mental Health (NIMH, K23MH106037). Mr. Dobson received support from the American Academy of Child and Adolescent Psychiatry Campaign for America{\textquoteright}s Kids and the Child and Adolescent Multimodal Study was supported by NIMH grants U01 MH064089 ( JTW), U01 MH64092 (AMA), U01 MH64003 (BB, SNC), U01 MH63747 (PCK), U01 MH64107 ( JM), and U01 MH64088 ( JP). Funding Information: Dr. Strawn has received research support from Edgemont, Eli Lilly, Shire, Forest Research Institute, Lundbeck, Neuronetics, and the National Institute of Mental Health (NIMH, K23MH106037). He receives royalties from Springer Publishing for two texts and has received material support from Assurex. Mr. Dobson has received support from the American Academy of Child & Adolescent Psychiatry (AACAP) (Campaign for America{\textquoteright}s Kids). Dr. Rynn has received support from NIH, NIMH, the National Institute of Child Health and Human Development (NICHD), Eli Lilly and Co., Pfizer, Merck, and Shire. She has served as a consultant to Shire and has received royalties from American Psychiatric Publishing and a writing fee from Oxford University Press. She has received honoraria from AACAP and the American Society of Clinical Psychopharmacology in addition to fees for academic lectures. Dr. Walkup has received grant support from the Hartwell Foundation and the Tourette Syndrome Association. He has served as a consultant to Shire. He has received free medication and placebo from Eli Lilly and Co., Pfizer, and Abbott for NIMH-funded studies. He has served on the advisory board and speakers{\textquoteright} bureau of the Tourette Syndrome Association. He has received royalties from Guilford Press and Oxford University Press for books on Tourette syndrome. He has received an honorarium and travel support for an educational meeting from the Tourette Syndrome Association. He also has received travel support for an unpaid position on the Medical Advisory Board of the Tourette Syndrome Association. He is an unpaid member of the Scientific Advisory Board of the Trichotillomania Learning Center, the Scientific Council of the Anxiety and Depression Association of America, and a Scientific Advisor to the American Foundation of Suicide Prevention. Dr. Compton has received research support from NIMH, NARSAD, Shire Pharmaceuticals, and Mursion, Inc. He has received honoraria from the Nordic Long-Term Obsessive-Compulsive Disorder (OCD) Treatment Study Research Group and serves as an associated editor for Journal of Consulting and Clinical Psychology (until mid 2016), Journal of Child and Adolescent Psychopharmacology, and BMC Psychiatry. He has provided expert testimony at Duke Forensic Group. Dr. Sakolsky has received research support from NIMH and the National Alliance for Research on Schizophrenia and Depression (NARSAD). She has received honoraria from AACAP for teaching at the 2012 Annual Review Course. She has served as an editorial board member of Child and Adolescent Psychopharmacology News and is a specialty consultant for the Prescriber{\textquoteright}s Letter. Dr. Kendall has received grant support from NIMH and NICHD. He has received royalties from publication of anxiety treatment materials and books on child mental health from Guilford Press, Ericsson, Workbook Publishing, and Oxford University Press. He has received honoraria from lectures on the topic of anxiety in youth. Dr. McCracken has received research support from NIMH, NICHD, Maternal and Child Health Bureau, Seaside Therapeutics, and Roche. He has served as a consultant to Bio-Marin and Roche. He has received speaker honoraria from the Tourette Syndrome Association Speaker{\textquoteright}s Bureau, the Nevada Psychiatric Association, and AACAP. He has received study drug and placebo from Shire. Dr. Ginsburg has received grant support from NIMH and book royalties from Oxford University Press. Dr. Albano has received research grant support from NIMH, Duke University Research Institute, and private donors. She has received royalties from Oxford University Press, Lynn Sonberg Books, and Penguin/Avery Press. She has received honoraria from the American Psychological Association and consultant fees from Brackett Global. She is an unpaid member of the data safety monitoring board for IMPACT, a study through Cambridge University, United Kingdom. She is also an unpaid board of directors and scientific advisory board member of the Anxiety and Depression Association of America. Dr. Piacentini has received grant or research support from NIMH, Pfizer Pharmaceuticals through the Duke University Child and Adolescent Psychiatry Trials Network (CAPTN), the Tourette Syndrome Association, and private donors. He has served on the advisory boards (unpaid) and received speaking honoraria and travel reimbursement from the International Obsessive-Compulsive Disorder Foundation and Trichotillomania Learning Center. He has served on the advisory boards (unpaid) and received speaking honoraria from the Anxiety Depression Association of America. He has received speaking honoraria and travel reimbursement from the Tourette Syndrome Association. He has received book royalties from Guilford Press and Oxford University Press. He is a coauthor of several assessment tools, all of which are in the public domain, and therefore no royalties are received. Dr. Birmaher has received grant support from NIMH and book royalties from Random House, Inc., Lippincott Williams and Wilkins, and UpToDate. Finally, views expressed within this article represent those of the authors and are not intended to represent the position of NIMH, the National Institutes of Health (NIH), or the Department of Health and Human Services. Publisher Copyright: Copyright {\textcopyright} 2017, Mary Ann Liebert, Inc.",
year = "2017",
month = aug,
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",
}
