{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T09:36:47Z","timestamp":1791020207781,"version":"4.1.0"},"reference-count":12,"publisher":"American Medical Association (AMA)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Psychiatry"],"published-print":{"date-parts":[[2025,6,1]]},"abstract":"Importance<\/jats:title>Analyzing effects within placebo groups allows for transdiagnostic comparisons, as placebo is the only substance systematically studied across all major psychiatric diagnoses. Recently, the study team meta-analytically showed that improvement under placebo varies across major psychiatric diagnoses. However, comprehensive transdiagnostic comparisons of negative effects under placebo (nocebo effects) are lacking.<\/jats:p><\/jats:sec>Objective<\/jats:title>To compare premature study termination rates in placebo groups of high-quality randomized clinical trials (RCTs) across 9 major psychiatric disorders, focusing on total dropouts, dropouts due to adverse events, and dropouts due to lack of effect.<\/jats:p><\/jats:sec>Data Sources<\/jats:title>This analysis is part of a broader research project using a systematic approach to identifying the most recent high-quality systematic review for each diagnosis (Open-Science-Foundation preregistered: u469a<\/jats:ext-link>).<\/jats:p><\/jats:sec>Study Selection<\/jats:title>From these reviews, the 10 highest quality and most recent placebo-controlled RCTs were selected for each diagnosis, totaling 90 RCTs.<\/jats:p><\/jats:sec>Data Extraction and Synthesis<\/jats:title>Searches and data extraction were conducted according to the Cochrane Handbook. Pooled dropout rates (DRs) with 95% CIs were calculated.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>The primary outcome was total DR per diagnosis, determined in random-effects meta-analyses. Diagnostic differences were tested for statistical significance using Q<\/jats:italic> tests. Potential confounders were examined in multivariable meta-regression analyses.<\/jats:p><\/jats:sec>Results<\/jats:title>Eighty-six of the 90 studies reported total DRs (10\u202f056 participants). DR differed between diagnoses (Q<\/jats:italic>\u2009=\u200982.2; df<\/jats:italic>\u2009=\u20098; P<\/jats:italic>\u2009&amp;lt;\u2009.001), with schizophrenia (DR, 0.41; 95% CI, 0.35-0.48), panic disorder, and mania showing the highest rates, and posttraumatic stress disorder, major depressive disorder (MDD), and attention-deficit\/hyperactivity disorder (ADHD) (DR, 0.17; 95% CI, 0.11-0.25) had the lowest. Schizophrenia and mania also had the highest DR due to lack of effect, while ADHD and MDD had the lowest (Q<\/jats:italic>\u2009=\u200971.3; df<\/jats:italic>\u2009=\u20098; P<\/jats:italic>\u2009&amp;lt;\u2009.001). Most dropouts due to adverse events occurred in obsessive-compulsive disorder (DR, 0.07; 95% CI, 0.05-0.09) and panic disorder studies and the fewest occurred in MDD and ADHD trials (Q<\/jats:italic>\u2009=\u200932.1; df<\/jats:italic>\u2009=\u20098; P<\/jats:italic>\u2009&amp;lt;\u2009.001). Meta-regression revealed no additional associated factors on DRs.<\/jats:p><\/jats:sec>Conclusion and Relevance<\/jats:title>These findings indicate that placebo treatment is associated with adverse effects that differ among psychiatric diagnoses. The main negative effect was lack of effect, with diagnostic variations corroborating findings on positive placebo response from earlier analyses. Schizophrenia had the least favorable course under placebo, while MDD demonstrated the most favorable.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamapsychiatry.2025.0336","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T15:00:47Z","timestamp":1744815647000},"page":"618","source":"Crossref","is-referenced-by-count":5,"title":["Negative Effects During Placebo Treatment"],"prefix":"10.1001","volume":"82","author":[{"given":"Tom","family":"Bschor","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Hospital, Technical University of Dresden, Dresden, Germany"},{"name":"Government Commission for Modern and Needs-Based Hospital Care, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine","family":"Unger","sequence":"additional","affiliation":[{"name":"Social Psychiatric Service, Berlin district of Reinickendorf, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Nagel","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Hospital, Technical University of Dresden, Dresden, Germany"},{"name":"Federal Joint Committee (G-BA), Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Schwarzer","sequence":"additional","affiliation":[{"name":"Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Baethge","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"8","key":"ybr250003r1","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1001\/jamapsychiatry.2024.0994","article-title":"Differential outcomes of placebo treatment across 9 psychiatric disorders: a systematic review and meta-analysis.","volume":"81","author":"Bschor","year":"2024","journal-title":"JAMA Psychiatry"},{"key":"ybr250003r2","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1146\/annurev-pharmtox-022723-112425","article-title":"The nocebo effect.","volume":"64","author":"Colloca","year":"2024","journal-title":"Annu Rev Pharmacol Toxicol"},{"issue":"6","key":"ybr250003r3","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1056\/NEJMra1907805","article-title":"Placebo and Nocebo Effects.","volume":"382","author":"Colloca","year":"2020","journal-title":"N Engl J Med"},{"issue":"6","key":"ybr250003r4","doi-asserted-by":"publisher","first-page":"702","DOI":"10.4088\/JCP.13r08858","article-title":"Nocebo effects in the treatment of major depression: results from an individual study participant-level meta-analysis of the placebo arm of duloxetine clinical trials.","volume":"76","author":"Dodd","year":"2015","journal-title":"J Clin Psychiatry"},{"issue":"2","key":"ybr250003r5","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1111\/bdi.12662","article-title":"Incidence and characteristics of the nocebo response from meta-analyses of the placebo arms of clinical trials of olanzapine for bipolar disorder.","volume":"21","author":"Dodd","year":"2019","journal-title":"Bipolar Disord"},{"key":"ybr250003r6","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.jad.2017.03.024","article-title":"Placebo and nocebo reactions in randomized trials of pharmacological treatments for persistent depressive disorder. 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