{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:07:23Z","timestamp":1768568843114,"version":"3.49.0"},"posted":{"date-parts":[[2024,11,5]]},"group-title":"Neurology","reference-count":30,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T00:00:00Z","timestamp":1730764800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,11,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>BACKGROUND<\/jats:title>\n                  <jats:p>Multiple System Atrophy (MSA) is a rapidly progressive and fatal neurodegenerative disease, with no effective treatment. Estimating the placebo and nocebo responses will help better design and interpret clinical trials.<\/jats:p>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To estimate the placebo and nocebo responses in MSA and explore their determinants.<\/jats:p>\n                  <\/jats:sec>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>Electronic databases were searched up to November 2020. Randomized, blinded, placebo- or sham-controlled trials of patients with MSA were included if quantitative data were extractable on the placebo arm. The primary outcomes were: placebo response, defined as the within-group change from baseline, using any scale measuring motor outcomes; and nocebo response, defined as the proportion of patients experiencing adverse effects in the placebo arm. Random-effects meta-analyses were used to pool data. Several predetermined subgroup analyses and metaregressions were performed. PROSPERO registration number: CRD42021222915.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>\n                    We included 21 randomized controlled trials (614 participants). Pooled placebo response was an increase in the Unified MSA Rating Scale (UMSARS) parts I and II of 9.09 points (95% CI 7.78 to 10.31, I\n                    <jats:sup>2<\/jats:sup>\n                    =94.00%, 9 studies, 304 participants). Pooled nocebo response was 63,88% (CI 95% 41.15 to 84.05, I\n                    <jats:sup>2<\/jats:sup>\n                    =93.03%, 13 studies, 331 participants). Both placebo and nocebo responses were greater in trials with longer duration, whereas nocebo response was also higher in studies testing pharmacological interventions when compared with non-pharmacological interventions.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>There may be a favorable response associated with the placebo, but this data needs to be compared with a \u201cno treatment group\u201d in order to validate its real impact. The nocebo response is high and should be considered in future clinical trial design and interpretation.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.11.05.24316747","type":"posted-content","created":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T18:10:26Z","timestamp":1730830226000},"source":"Crossref","is-referenced-by-count":0,"title":["Placebo and Nocebo Responses in Multiple System Atrophy - a systematic review and meta-analysis of clinical trials"],"prefix":"10.64898","author":[{"given":"Afonso Pessoa","family":"de Amorim","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5567-7938","authenticated-orcid":false,"given":"Filipe B","family":"Rodrigues","sequence":"additional","affiliation":[]},{"given":"Ana","family":"Castro-Caldas","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3950-5113","authenticated-orcid":false,"given":"Joaquim J","family":"Ferreira","sequence":"additional","affiliation":[]}],"member":"54368","reference":[{"key":"2024110818301339000_2024.11.05.24316747v1.1","first-page":"7","volume":"8","year":"2009","journal-title":"Multiple system atrophy: an update"},{"key":"2024110818301339000_2024.11.05.24316747v1.2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29005"},{"key":"2024110818301339000_2024.11.05.24316747v1.3","unstructured":"Po\u017egain I , Po\u017egain Z , Degme D. 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