Effects of open-label placebos across populations and outcomes: an updated systematic review and meta-analysis of randomized controlled trials

Abstract This work synthesizes and updates findings from previous systematic-reviews and meta-analyses on open-label placebos (OLPs). For the first time, it directly tests whether OLPs differ in effects between clinical and non-clinical samples, and between self-report and objective outcomes. We sea...

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Main Authors: Johannes C. Fendel, Carl Tiersch, Paul Sölder, Jens Gaab, Stefan Schmidt
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-14895-z
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author Johannes C. Fendel
Carl Tiersch
Paul Sölder
Jens Gaab
Stefan Schmidt
author_facet Johannes C. Fendel
Carl Tiersch
Paul Sölder
Jens Gaab
Stefan Schmidt
author_sort Johannes C. Fendel
collection DOAJ
description Abstract This work synthesizes and updates findings from previous systematic-reviews and meta-analyses on open-label placebos (OLPs). For the first time, it directly tests whether OLPs differ in effects between clinical and non-clinical samples, and between self-report and objective outcomes. We searched eight databases up to November 9, 2023, and included 60 randomized controlled trials (RCTs), compromising 63 separate comparisons. OLPs yielded a small positive effect across various health-related outcomes (k = 63, n = 4554, SMD = 0.35, CI 95% = 0.26; 0.44, p < 0.0001, I2 = 53%). The effect differed between clinical (k = 24, n = 1383, SMD = 0.47) and non-clinical samples (k = 39, n = 3171, SMD = 0.29; Q = 4.25, p < 0.05), as well as between self-reported (k = 55, n = 3919, SMD = 0.39) and objective outcomes (k = 17, n = 1250, SMD = 0.09; Q = 7.24, p < 0.01). Neithter the level of suggestiveness nor the type of control moderated the effect. These findings confirm that OLPs are effective for both clinical and non-clinical samples—particularly when effects are assessed via self-reports.
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spelling doaj-art-5b09d7ad1fc540aeaa4cc73de4b5ebee2025-08-20T03:46:08ZengNature PortfolioScientific Reports2045-23222025-08-0115111410.1038/s41598-025-14895-zEffects of open-label placebos across populations and outcomes: an updated systematic review and meta-analysis of randomized controlled trialsJohannes C. Fendel0Carl Tiersch1Paul Sölder2Jens Gaab3Stefan Schmidt4Department of Psychosomatic Medicine and Psychotherapy, Faculty of Medicine, Medical Center - University of Freiburg, University of FreiburgDivision of Clinical Psychology and Psychotherapy, Faculty of Psychology, University of BaselCognition, Action and Sustainability Unit, Department of Psychology, University of FreiburgDivision of Clinical Psychology and Psychotherapy, Faculty of Psychology, University of BaselDepartment of Psychosomatic Medicine and Psychotherapy, Faculty of Medicine, Medical Center - University of Freiburg, University of FreiburgAbstract This work synthesizes and updates findings from previous systematic-reviews and meta-analyses on open-label placebos (OLPs). For the first time, it directly tests whether OLPs differ in effects between clinical and non-clinical samples, and between self-report and objective outcomes. We searched eight databases up to November 9, 2023, and included 60 randomized controlled trials (RCTs), compromising 63 separate comparisons. OLPs yielded a small positive effect across various health-related outcomes (k = 63, n = 4554, SMD = 0.35, CI 95% = 0.26; 0.44, p < 0.0001, I2 = 53%). The effect differed between clinical (k = 24, n = 1383, SMD = 0.47) and non-clinical samples (k = 39, n = 3171, SMD = 0.29; Q = 4.25, p < 0.05), as well as between self-reported (k = 55, n = 3919, SMD = 0.39) and objective outcomes (k = 17, n = 1250, SMD = 0.09; Q = 7.24, p < 0.01). Neithter the level of suggestiveness nor the type of control moderated the effect. These findings confirm that OLPs are effective for both clinical and non-clinical samples—particularly when effects are assessed via self-reports.https://doi.org/10.1038/s41598-025-14895-zOpen-label placeboObjective outcomeMeta-analysisSystematic-review
spellingShingle Johannes C. Fendel
Carl Tiersch
Paul Sölder
Jens Gaab
Stefan Schmidt
Effects of open-label placebos across populations and outcomes: an updated systematic review and meta-analysis of randomized controlled trials
Scientific Reports
Open-label placebo
Objective outcome
Meta-analysis
Systematic-review
title Effects of open-label placebos across populations and outcomes: an updated systematic review and meta-analysis of randomized controlled trials
title_full Effects of open-label placebos across populations and outcomes: an updated systematic review and meta-analysis of randomized controlled trials
title_fullStr Effects of open-label placebos across populations and outcomes: an updated systematic review and meta-analysis of randomized controlled trials
title_full_unstemmed Effects of open-label placebos across populations and outcomes: an updated systematic review and meta-analysis of randomized controlled trials
title_short Effects of open-label placebos across populations and outcomes: an updated systematic review and meta-analysis of randomized controlled trials
title_sort effects of open label placebos across populations and outcomes an updated systematic review and meta analysis of randomized controlled trials
topic Open-label placebo
Objective outcome
Meta-analysis
Systematic-review
url https://doi.org/10.1038/s41598-025-14895-z
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