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Meta-analysis of the placebo response in antidepressant trials.
Abstract
Unlabelled Improvements in placebo groups of antidepressant trials account for a major part of the expected drug effects. We aimed to determine overall effect sizes of placebo and drug effects in antidepressant trials, and to analyze whether the placebo effect in antidepressant trials also occurs for patient self-perception, general psychopathology, and quality of life.Methods Search terms covered different variants of pharmacotherapy for patients with depressive disorders from January 1980 to December 2005 in the databases Medline/Pubmed, PsychInfo and CENTRAL, a.o. We included RCTs with a placebo group and an antidepressant group in people with depression.Results We computed within group effect sizes for several outcome variables and integrated them using random-effect models. A total of 96 studies were included. Mean effect size in the placebo group for primary outcome variables was d=1.69 (95% CI=1.54-1.84) compared to 2.50 in the drug group (95% CI=2.30-2.69). There was a major difference between placebo effect sizes assessed with observer ratings (d=1.85, 95% CI=1.69-2.01) versus patient self-perception (d=0.67; 95% CI=0.49-0.85). The effect sizes in placebo groups in 2005 were more than twice as great as those in 1980, but only for observer ratings, not for patient self-ratings. The result was partly due to increased homogeneity of samples of recently published trials.Conclusions The placebo effect accounted for 68% of the effect in the drug groups. Whereas clinical trials need to control the placebo effect, clinical practice should attempt to use its full power.
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“A meta-analysis showed that the placebo response in antidepressant trials is approximately 68%,72 although this effect is not clear yet in light therapy trials specifically.”
From Effects of bright light therapy for depression during pregnancy: a randomised, double-blind controlled trial (2020) · cites this paper as [72]
In the citing paper
“However, several large-scale meta-analyses have recently suggested that the effectiveness of antipsychotic and antidepressant medications is only marginally different from that of a placebo (Leucht et al., 2009; Rief et al., 2009), and neither have been able to successfully remediate cognitive dysfunction (Keefe et al., 2013, 2014; Solé et al., 2015).”
From Aerobic Exercise as a Tool to Improve Hippocampal Plasticity and Function in Humans: Practical Implications for Mental Health Treatment (2016) · cites this paper as Rief et al., 2009
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Metadata
- Authors
- Rief, W., Nestoriuc, Y., Weiss, S., Welzel, E., Barsky, A. J., & Hofmann, S. G.
- Affiliations
- Philipps University of Marburg (DE)
- Brigham and Women's Hospital (US)
- Boston University (US)
- Corresponding author
- Rief, Winfried
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2009-11
- Volume
- 118
- Issue
- 1-3
- Pages
- 1-8
- ISSN
- 0165-0327 (ISSN-L)
- OpenAlex
- W2020001299
- Cited by
- 346
- References
- 46
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 21 · 2023: 20 · 2022: 25 · 2021: 10 · 2020: 23 · 2019: 15 · 2018: 48 · 2017: 23 · 2016: 19 · 2015: 23 · 2014: 24 · 2013: 26 · 2012: 11
- FWCI
- 1.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Affective Disorders (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
- Keywords
- placebo response, antidepressants, depression, placebo effect, antidepressant trials, observer ratings, patient self-perception, quality of life, psychopathology, effect size
- MeSH terms
- Antidepressive Agents, Depressive Disorder, Humans, Placebo Effect, Randomized Controlled Trials as Topic
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