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. 2022 Jun;32(5):278-287.
doi: 10.1089/cap.2021.0111.

A Characterization of the Clinical Global Impression Scale Thresholds in the Treatment of Adolescent Depression Across Multiple Rating Scales

Carl Y Zhang  1 , Jennifer L Vande Voort  2 , Deniz Yuruk  2 , Jeffrey A Mills  3 , Graham J Emslie  4   5 , Betsy D Kennard  4 , Taryn Mayes  4 , Madhukar Trivedi  4 , William V Bobo  6 , Jeffrey R Strawn  7 , Arjun P Athreya  1 , Paul E Croarkin  2
Affiliations

A Characterization of the Clinical Global Impression Scale Thresholds in the Treatment of Adolescent Depression Across Multiple Rating Scales

Carl Y Zhang et al. J Child Adolesc Psychopharmacol. 2022 Jun.

Abstract

Introduction: The Clinical Global Impressions-Improvement (CGI-I) scale is widely used in clinical research to assess symptoms and functioning in the context of treatment. The correlates of the CGI-I with efficacy scales for adolescent major depressive disorder are poorly understood. This study focused on benchmarking CGI-I scores with changes in the Children's Depression Rating Scale-Revised (CDRS-R) and the Quick Inventory of Depressive Symptomatology-Adolescent (17-item) Self-Report (QIDS-A17-SR). Methods: We examined three datasets with the clinician-rated CDRS-R to ascertain equivalent percent changes in total scores and CGI-I ratings. Exploratory analyses examined corresponding percentage changes in the QIDS-A17-SR and the CGI-I ratings. The CGI-I was the reference scale for nonparametric equipercentile linking with the Equate package in R. Results: CGI-I scores of 1 mapped to ≥78%-95% change in CDRS-R scores at 4-6 weeks across three datasets. CGI-I scores of 2 mapped to 56%-94% change in CDRS-R scores at 4-6 weeks across three studies. CGI-I scores of 3 mapped to 30%-68% changes in CDRS-R scores at 4-6 weeks across three studies. CGI-I scores of 4 mapped to a range of 29%-44% at 4-6 weeks across three studies. There was no significant difference (p ≥ 0.6) between treatment groups in both the Treatment of Adolescents with Depression and Treatment of Resistant Depression in Adolescents studies, for each CGI-I score ( = 1, or = 2 or = 3, or ≥4), associated mapping of total depression severity score, or associated percent change from baseline for corresponding follow-up visits. There was no significant sex difference (p > 0.2) in CGI-I linkages to CDRS-R total or percentage changes. Conclusions: These findings establish clear relationships among CGI-I scores and the CDRS-R and the QIDS-A17-SR. These benchmarks have utility for clinical trial study design, inter-rater reliability training, and clinical implementation.

Keywords: AMOD; TADS; TORDIA; equipercentile linking; remission; response.

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Conflict of interest statement

J.L.V.V. was a co-primary investigator on an investigator-initiated study that had grant-in-kind support for supplies and genotyping from Assurex Health. J.A.M. receives research support from the Yung Family Foundation. G.J.E. receives research support from Duke University, Forest Research Institute (partner of Merck KGaA; formerly known as Forest Laboratories), and Janssen Pharmaceuticals, Research & Development.

G.J.E. is a consultant for Lundbeck, Neuronetics, and Otsuka. B.D.K. receives royalties from Guilford Press, Inc., M.T. has provided consulting services to Acadia Pharmaceuticals, Inc., Alkermes, Inc., Allergan, Inc., Alto Neuroscience, Inc., Applied Clinical Intelligence, Axsome Therapeutics, Boehringer Ingelheim, Engage Health Media, GH Research Limited, GreenLight VitalSign6, Inc., Health Care Global Village, Janssen, Merck Sharp & Dohme Corp., Myriad Neuroscience, Navitor Pharmaceutical, Inc., Neurocrine Biosciences, Inc., Orexo US, Inc., Otsuka, Perception Neuroscience, Pharmerit International, SAGE Therapeutics, Signant Health, and Titan Pharmaceuticals, Inc. He has received grant/research funding from NIMH, NIDA, Patient-Centered Outcomes Research Institute (PCORI), and Cancer Prevention Research Institute of Texas (CPRIT).

In addition, he has received editorial compensation from Oxford University Press. W.V.B.'s research has been supported by the NIMH, AHRQ, NSF, Mayo Foundation for Medical Education and Research, and the Myocarditis Foundation; he has contributed chapters to UpToDate on the treatment of bipolar disorders. J.R.S. has received research support from Edgemont, Shire, Forest Research Institute, Otsuka, the Yung Family Foundation, and the National Institutes of Health (NICHD, NIMH, and NIEHS). He receives royalties from Springer Publishing for two texts and has received material support from Myriad genetics and honoraria from CMEology and Neuroscience Educational Institute. He provides consultation to the U.S. Food and Drug Administration as a Special Government Employee. A.A. receives research support from the Mayo Foundation for Medical Education and Research and NSF.

P.E.C. has received research grant support from Mayo Foundation for Education and Research, Neuronetics, Inc.; NeoSync, Inc.; NSF, NIMH, and Pfizer, Inc. He has received grant-in-kind (equipment support for research studies) from Assurex; MagVenture, Inc; and Neuronetics, Inc. He has served as a consultant for Engrail Therapeutics, Myriad Neuroscience, Procter & Gamble, and Sunovion. The other authors have no disclosure or potential conflict of interests.

Figures

FIG. 1.
FIG. 1.
Equipercentile linkage based on concordance between CGI-I score and percent change in CDRS-R total score from baseline, and CDRS-R total score at follow-up time points in (A) TADS (patients receiving fluoxetine or fluoxetine+CBT), (B) AMOD, and (C) TORDIA, including patients who received CBT+SSRI, CBT+SNRI, SNRI, and SSRI. AMOD, Adolescent Management of Depression; CBT, cognitive behavioral therapy; CDRS-R, Children's Depression Rating Scale-Revised; CGI-I, Clinical Global Impression-Improvement; TADS, Treatment for Adolescents with Depression Study; TORDIA, Treatment of SSRI-Resistant Depression in Adolescents.
FIG. 2.
FIG. 2.
Equipercentile liking plotted as lines based on concordance between CGI-I (CGI-I and percent change in QIDS-A17-SR total score from baseline) and CDRS-R total score at follow-up time points in AMOD study, wherein in (A), patients are not stratified, and in (B), patients are stratified by median split. AMOD, Adolescent Management of Depression; CDRS-R, Children's Depression Rating Scale-Revised; CGI-I, Clinical Global Impression-Improvement; QIDS-A17-SR, Quick Inventory of Depressive Symptomatology-Adolescent (17-item) Self-Report.
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