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Is placebo response in antidepressant trials rising or not? A reanalysis of datasets to conclude this long-lasting controversy
  1. Toshi A Furukawa1,
  2. Andrea Cipriani2,3,
  3. Stefan Leucht4,
  4. Lauren Z Atkinson2,3,
  5. Yusuke Ogawa1,
  6. Nozomi Takeshima1,
  7. Yu Hayasaka1,
  8. Anna Chaimani5,6,7,
  9. Georgia Salanti8
  1. 1 Departments of Health Promotion and Human Behavior and Clinical Epidemiology, Kyoto University Graduate School of Medicine/ School of Public Health, Kyoto, Japan
  2. 2 Department of Psychiatry, University of Oxford, Oxford, UK
  3. 3 Oxford Health NHS Foundation Trust, Oxford, UK
  4. 4 Department of Psychiatry and Psychotherapy, Technische Universität München, Klinikum rechts der Isar, Munich, Germany
  5. 5 School of Medicine, Paris Descartes University, Paris, France
  6. 6 INSERM, UMR1153 Epidemiology and Statistics, Sorbonne Paris Cité Research Center (CRESS), METHODS Team, Paris, France
  7. 7 Cochrane France, Paris, France
  8. 8 Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
  1. Correspondence to Dr Toshi A Furukawa, Departments of Health Promotion and Human Behavior and of Clinical Epidemiology, Kyoto University Graduate School of Medicine and School of Public Health, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan; furukawa{at}


It had long been believed that placebo response rates in antidepressant trials have been increasing and that they were responsible for rising numbers of so-called failed antidepressant trials. Two recent systematic reviews examined this issue and reached completely opposite findings. Furukawa and colleagues in a paper published in 2016 found that the placebo response rates are stable since 1991 and the apparent increase up to 2000 was confounded by changes in trial design features. By contrast, Khan and colleagues more recently concluded that placebo response rates had grown steadily in the past 30 years. The two reviews differed in the datasets they used, definitions of placebo response and statistical analyses. In this perspective article, we examined if such differences were responsible for the two reviews’ contrasting conclusions. Our reanalyses confirmed our previous results. We found that in any dataset and for any placebo response definition, there was no increase in placebo response over the years when the analysis was adjusted for the confounders related to study design features or when it was limited to studies published after 1990s. We conclude that placebo response in antidepressant trials has remained stable for the past 25 years, during which time the large majority of the studies have come to share similar design features.

  • depression & mood disorders

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  • Competing interests TAF has received lecture fees from Eli Lilly, Janssen, Meiji, MSD, Pfizer and Tanabe-Mitsubishi and consultancy fees from Takeda Science Foundation. He has received royalties from Igaku-Shoin and Nihon Bunka Kagaku-sha publishers. He has received grant or research support from Mochida and Tanabe-Mitsubishi. AC was expert witness for Accord Healthcare for a patent issue about quetiapine extended release. SL has received honoraria for lectures from Eli Lilly, Lundbeck (Institute), Pfizer, Janssen, BMS, Johnson and Johnson, Otsuka, Roche, SanofiAventis, ICON, Abbvie, AOP Orphan, Servier; for consulting/advisory boards from Roche, Janssen, Lundbeck, Eli Lilly, Otsuka, TEVA; for the preparation of educational material and publications from Lundbeck Institute and Roche. Eli Lilly has provided medication for a clinical trial led by SL as principal investigator. All the other authors declare no competing interests.

  • Provenance and peer review Commissioned; externally peer reviewed.