Contribution of spontaneous improvement to placebo response in depression: A meta-analytic review

Rutherford, Bret R.; Mori, Shoko; Sneed, Joel R.; Pimontel, Monique A.; Roose, Steven P.

doi:10.1016/j.jpsychires.2012.02.008

Cited by 79Pain Management and Placebo EffectPsychotherapy Techniques and ApplicationsTreatment of Major Depression

Contribution of spontaneous improvement to placebo response in depression: A meta-analytic review

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Rutherford, Bret R., Mori, Shoko, Sneed, Joel R., Pimontel, Monique A., Roose, Steven P.·2012·Journal of Psychiatric Research

DOI 10.1016/j.jpsychires.2012.02.008PMC PMC3509755

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Abstract

Objectives It is unknown to what degree spontaneous improvement accounts for the large placebo response observed in antidepressant trials for Major Depressive Disorder (MDD). The purpose of this study was to estimate the spontaneous improvement observed in treatment-seeking individuals with acute MDD by determining the symptom change in depressed patients assigned to wait-list controls in psychotherapy studies.Method The databases PubMed and PsycINFO were searched to identify randomized, prospective studies randomizing outpatients to psychotherapy or a wait-list control condition for the treatment of acute MDD. Standardized effect sizes calculated from each identified study were aggregated in a meta-analysis to obtain a summary statistic for the change in depression scores during participation in a wait-list control.Results Ten trials enrolling 340 participants in wait-list control conditions were identified. The estimated effect size for the change in depression scores during wait-list control was 0.505 (95% CI 0.271-0.739, p < 0.001), representing an average improvement of 4 points on the Hamilton Rating Scale for Depression.Discussion Depressed patients acutely experience improvement even without treatment, but spontaneous improvement is unlikely to account for the magnitude of placebo response typically observed in antidepressant trials. These findings must be interpreted in light of the small number wait-list control participants available for analysis as well as certain methodological heterogeneity in the psychotherapy studies analyzed.

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Previous meta-analyses have demonstrated that control group responses can negatively influence antidepressant efficacy.
“Whilst previous meta-analyses have demonstrated that control group responses (CGRs) can negatively influence antidepressant efficacy”
From Challenges establishing the efficacy of exercise as an antidepressant treatment: a systematic review and meta-analysis of control group responses in exercise randomised controlled trials (2016) · cites this paper as [17]
The improvement in control groups of exercise RCTs is approximately double that reported in control groups of antidepressant studies (4 points on HAM-D).
“The improvement in control groups equates to approximately double that reported in control groups of antidepressant studies.”
From Challenges establishing the efficacy of exercise as an antidepressant treatment: a systematic review and meta-analysis of control group responses in exercise randomised controlled trials (2016) · cites this paper as [17]

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Authors: Rutherford, B. R., Mori, S., Sneed, J. R., Pimontel, M. A., & Roose, S. P.
Affiliations: New York State Psychiatric Institute (US)
Queens College, CUNY (US)
Corresponding author: Rutherford, Bret R.
ORCID: Rutherford, Bret R.
Mori, Shoko
Sneed, Joel R.
Pimontel, Monique A.
Venue: Journal of Psychiatric Research
Publisher: Elsevier BV
Published: 2012-06
Volume: 46
Issue: 6
Pages: 697-702
ISSN: 0022-3956 (ISSN-L)
DOI: 10.1016/j.jpsychires.2012.02.008
PMC: PMC3509755
OpenAlex: W2169130856
Cited by: 79
References: 49
Citations by year: 2026: 3 · 2025: 1 · 2024: 5 · 2023: 4 · 2022: 3 · 2021: 3 · 2020: 5 · 2019: 7 · 2018: 3 · 2017: 8 · 2016: 9 · 2015: 9 · 2014: 10 · 2013: 6 · 2012: 2
FWCI: 4.37
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Journal of Psychiatric Research (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Hope for Depression Research Foundation
National Institutes of Health
National Institute of Mental Health (R21MH087774, K23MH075006, K23MH085236, T32MH015144)
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords: spontaneous improvement, placebo response, major depressive disorder, waitlist control, psychotherapy, antidepressant trials, Hamilton Depression Rating Scale, treatment-seeking patients, symptom change
MeSH terms: Antidepressive Agents, Depression, Humans, Placebo Effect, Databases, Bibliographic

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Contribution of spontaneous improvement to placebo response in depression: A meta-analytic review

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