TY - JOUR
T1 - The Impact of Failed Antidepressant Trials on Outcomes in Children and Adolescents with Anxiety and Depression
T2 - A Systematic Review and Meta-Analysis
AU - Mossman, Sarah A.
AU - Mills, Jeffrey A.
AU - Walkup, John T.
AU - Strawn, Jeffrey R.
N1 - Funding Information:
1Anxiety Disorders Research Program, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. 2Department of Economics, Carl H. Lindner College of Business at the University of Cincinnati, Cincinnati, Ohio, USA. 3Department of Psychiatry and Behavioral Health, Robert and Anne Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. Presentations: These data were presented as a poster at the American Academy of Child and Adolescent Psychiatry’s 66th Annual Meeting, Chicago, IL, October 14–19, 2019. Funding: This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Development (NICHD) through Grants R01HD098757 and R01HD099775 and by the Yung Family Foundation.
Publisher Copyright:
© Copyright 2021, Mary Ann Liebert, Inc., publishers 2021.
PY - 2021/5
Y1 - 2021/5
N2 - Objective: To identify predictors of medication-placebo differences in double-blind placebo-controlled antidepressant trials in children and adolescents with anxiety and depression. Methods: Clinical trials in patients <18 years of age with major depressive disorder or generalized, separation or social anxiety disorders were obtained from PubMed, the Cochrane Database and clinicaltrials.gov searches from inception through 2019. Forty-nine trials (43 published and 6 unpublished) of anxiety (κ = 13) and depression (κ = 36) evaluated 19 antidepressants in 8642 child and adolescent patients; placebo and medication response rates, trial characteristics, disorder, medication class, and funding source were extracted. Antidepressant-placebo differences were examined using Bayesian hierarchical models and estimates of response were determined for trial design, disorder, and medication class variables. Using meta-regression, correlates of antidepressant-placebo difference and placebo response were examined. Results: Funding source differentiated medication-placebo differences regardless of disorder. Industry trials had larger placebo response rates (mean difference: 0.189 ± 0.066, credible interval [CrI]: 0.067 to 0.33, p = 0.0008) and smaller medication-placebo differences (-0.235 ± 0.078, CrI: -0.397 to -0.086, p = 0.005) compared with federally funded trials. However, medication response was similar for industry- and federally-funded studies (-0.046 ± 0.042, CrI: -0.130 to 0.038, p = 0.252). Conclusions: The impact of study sponsorship on trial outcome supports the assertion that industry-funded trials with high placebo response rates and small drug-placebo differences are "failed trials"and should not be described as "negative trials"or used to determine public health estimates of antidepressant efficacy in children and adolescents with anxiety and depression. Identifying the proper role and value of industry-funded trials is critical to establishing the evidence base for antidepressants in youth.
AB - Objective: To identify predictors of medication-placebo differences in double-blind placebo-controlled antidepressant trials in children and adolescents with anxiety and depression. Methods: Clinical trials in patients <18 years of age with major depressive disorder or generalized, separation or social anxiety disorders were obtained from PubMed, the Cochrane Database and clinicaltrials.gov searches from inception through 2019. Forty-nine trials (43 published and 6 unpublished) of anxiety (κ = 13) and depression (κ = 36) evaluated 19 antidepressants in 8642 child and adolescent patients; placebo and medication response rates, trial characteristics, disorder, medication class, and funding source were extracted. Antidepressant-placebo differences were examined using Bayesian hierarchical models and estimates of response were determined for trial design, disorder, and medication class variables. Using meta-regression, correlates of antidepressant-placebo difference and placebo response were examined. Results: Funding source differentiated medication-placebo differences regardless of disorder. Industry trials had larger placebo response rates (mean difference: 0.189 ± 0.066, credible interval [CrI]: 0.067 to 0.33, p = 0.0008) and smaller medication-placebo differences (-0.235 ± 0.078, CrI: -0.397 to -0.086, p = 0.005) compared with federally funded trials. However, medication response was similar for industry- and federally-funded studies (-0.046 ± 0.042, CrI: -0.130 to 0.038, p = 0.252). Conclusions: The impact of study sponsorship on trial outcome supports the assertion that industry-funded trials with high placebo response rates and small drug-placebo differences are "failed trials"and should not be described as "negative trials"or used to determine public health estimates of antidepressant efficacy in children and adolescents with anxiety and depression. Identifying the proper role and value of industry-funded trials is critical to establishing the evidence base for antidepressants in youth.
KW - antidepressant
KW - depression
KW - funding
KW - pediatric
KW - placebo response
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U2 - 10.1089/cap.2020.0195
DO - 10.1089/cap.2020.0195
M3 - Review article
C2 - 33887154
AN - SCOPUS:85106501243
SN - 1044-5463
VL - 31
SP - 259
EP - 267
JO - Journal of Child and Adolescent Psychopharmacology
JF - Journal of Child and Adolescent Psychopharmacology
IS - 4
ER -
