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Initial severity of depression and efficacy of cognitive–behavioural therapy: Individual-participant data meta-analysis of pill-placebo-controlled trials

Published online by Cambridge University Press:  02 January 2018

Toshi A. Furukawa
Departments of Health Promotion and Human Behavior and of Clinical Epidemiology, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan
Erica S. Weitz
Department of Clinical Psychology and EMGO Institute for Health and Care Research, VU University Amsterdam, The Netherlands
Shiro Tanaka
Department of Pharmacoepidemiology, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan
Steven D. Hollon
Department of Psychology, Vanderbilt University, Nashville, Tennessee, USA
Stefan G. Hofmann
Department of Psychological and Brain Science, Boston University, Massachusetts, USA
Gerhard Andersson
Department of Behavioural Sciences and Learning, Linköping University, Linköping, Sweden and Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Stokholm, Sweden
Jos Twisk
Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Amsterdam, The Netherlands
Robert J. DeRubeis
Department of Psychology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Sona Dimidjian
Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, USA
Ulrich Hegerl
Department of Psychiatry and Psychotherapy, University of Leipzig, Leipzig, Germany
Roland Mergl
Department of Psychiatry and Psychotherapy, University of Leipzig, Leipzig, Germany
Robin B. Jarrett
Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, Texas, USA
Jeffrey R. Vittengl
Department of Psychology, Truman State University, Kirksville, Missouri, USA
Norio Watanabe
Departments of Health Promotion and Human Behavior and of Clinical Epidemiology, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan
Pim Cuijpers
Department of Clinical Psychology and EMGO Institute for Health and Care Research, VU University Amsterdam, The Netherlands
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The influence of baseline severity has been examined for antidepressant medications but has not been studied properly for cognitive–behavioural therapy (CBT) in comparison with pill placebo.


To synthesise evidence regarding the influence of initial severity on efficacy of CBT from all randomised controlled trials (RCTs) in which CBT, in face-to-face individual or group format, was compared with pill-placebo control in adults with major depression.


A systematic review and an individual-participant data meta-analysis using mixed models that included trial effects as random effects. We used multiple imputation to handle missing data.


We identified five RCTs, and we were given access to individual-level data (n = 509) for all five. The analyses revealed that the difference in changes in Hamilton Rating Scale for Depression between CBT and pill placebo was not influenced by baseline severity (interaction P = 0.43). Removing the non-significant interaction term from the model, the difference between CBT and pill placebo was a standardised mean difference of –0.22 (95% CI –0.42 to –0.02, P = 0.03, I 2 = 0%).


Patients suffering from major depression can expect as much benefit from CBT across the wide range of baseline severity. This finding can help inform individualised treatment decisions by patients and their clinicians.

Review Articles
Copyright © Royal College of Psychiatrists, 2017 



These authors contributed equally to the work.

Declaration of interest

T.A.F. has received lecture fees from Eli Lilly, Meiji, Mochida, MSD, Otsuka, Pfizer and Tanabe-Mitsubishi and consultancy fees from Sekisui Chemicals and Takeda Science Foundation. He has received royalties from Igaku-Shoin, Seiwa-Shoten and Nihon Bunka Kagaku-sha publishers. He has received grant or research support from the Japanese Ministry of Education, Science and Technology, the Japanese Ministry of Health, Labour and Welfare, the Japan Society for the Promotion of Science, the Japan Foundation for Neuroscience and Mental Health, Mochida and Tanabe-Mitsubishi. He is diplomate of the Academy of Cognitive Therapy. U.H. has received lecture fees from Bristol-Myers Squibb, Medice Arzneimittel, Novartis and Roche Pharma and was an advisory board member for Lilly, Lundbeck, Takeda Pharmaceuticals, Servier and Otsuka Pharma. R.M. has served as a consultant for Nycomed, a Takeda company. R.B.J. received support from the NIMH for the trial cited here (R0MH45043) and is a paid consultant to NIH including the NIMH and to UpToDate. J.R.V. is a paid consultant to UpToDate. N.W. has received royalties from Sogensha and Paquet, and speaker fees and research funds from Asahi Kasei, Dai-Nippon Sumitomo, Eli Lilly, GlaxoSmithKline, Janssen, Meiji, MSD, Otsuka and Pfizer.


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