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Placebo Response in Trials of Negative Symptoms in Schizophrenia: A Critical Reassessment of the Evidence

BACKGROUND: Summarizing evidence from clinical trials of patients with schizophrenia with predominant or prominent negative symptoms (NS), a prior meta-analysis reported a large placebo effect in negative symptoms (Cohen’s d = 2.909). Assuming that such an effect was clinically not plausible, we per...

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Autores principales: Czobor, Pál, Kakuszi, Brigitta, Bitter, István
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9673255/
https://www.ncbi.nlm.nih.gov/pubmed/35713342
http://dx.doi.org/10.1093/schbul/sbac061
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author Czobor, Pál
Kakuszi, Brigitta
Bitter, István
author_facet Czobor, Pál
Kakuszi, Brigitta
Bitter, István
author_sort Czobor, Pál
collection PubMed
description BACKGROUND: Summarizing evidence from clinical trials of patients with schizophrenia with predominant or prominent negative symptoms (NS), a prior meta-analysis reported a large placebo effect in negative symptoms (Cohen’s d = 2.909). Assuming that such an effect was clinically not plausible, we performed a critical re-assessment and an update of the previous results with newly available data from add-on and monotherapy studies. STUDY DESIGN: Random-effect meta/regression analysis of trials that focused on predominant or prominent NS; and adopted a double-blind, randomized, placebo-controlled design. The final pooled meta-analytic database, based on the available add-on and monotherapy studies combined, included 24 publications containing data on a total of 25 studies (21 add-on, 4 monotherapy). STUDY RESULTS: The pooled overall estimate for the placebo effect from the primary analysis for all included studies had a medium effect size, with a Cohen’s d value of 0.6444 (SE = 0.091). The estimates were similar in the add-on and monotherapy studies. Meta-regression indicated that the high placebo response was significantly associated with clinical trial characteristics, including the high ratio of patients assigned to active vs. placebo treatment and short trial duration. CONCLUSIONS: These results represent a major downward correction for a current effect size estimate of the placebo response in the negative symptoms of schizophrenia. Our findings also pinpoint certain clinical trial characteristics, which may serve as important predictors of the placebo response. The knowledge of these factors can have important implications for drug development and trial design for new drugs for negative symptoms of schizophrenia.
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spelling pubmed-96732552022-11-21 Placebo Response in Trials of Negative Symptoms in Schizophrenia: A Critical Reassessment of the Evidence Czobor, Pál Kakuszi, Brigitta Bitter, István Schizophr Bull Regular Articles BACKGROUND: Summarizing evidence from clinical trials of patients with schizophrenia with predominant or prominent negative symptoms (NS), a prior meta-analysis reported a large placebo effect in negative symptoms (Cohen’s d = 2.909). Assuming that such an effect was clinically not plausible, we performed a critical re-assessment and an update of the previous results with newly available data from add-on and monotherapy studies. STUDY DESIGN: Random-effect meta/regression analysis of trials that focused on predominant or prominent NS; and adopted a double-blind, randomized, placebo-controlled design. The final pooled meta-analytic database, based on the available add-on and monotherapy studies combined, included 24 publications containing data on a total of 25 studies (21 add-on, 4 monotherapy). STUDY RESULTS: The pooled overall estimate for the placebo effect from the primary analysis for all included studies had a medium effect size, with a Cohen’s d value of 0.6444 (SE = 0.091). The estimates were similar in the add-on and monotherapy studies. Meta-regression indicated that the high placebo response was significantly associated with clinical trial characteristics, including the high ratio of patients assigned to active vs. placebo treatment and short trial duration. CONCLUSIONS: These results represent a major downward correction for a current effect size estimate of the placebo response in the negative symptoms of schizophrenia. Our findings also pinpoint certain clinical trial characteristics, which may serve as important predictors of the placebo response. The knowledge of these factors can have important implications for drug development and trial design for new drugs for negative symptoms of schizophrenia. Oxford University Press 2022-06-17 /pmc/articles/PMC9673255/ /pubmed/35713342 http://dx.doi.org/10.1093/schbul/sbac061 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Regular Articles
Czobor, Pál
Kakuszi, Brigitta
Bitter, István
Placebo Response in Trials of Negative Symptoms in Schizophrenia: A Critical Reassessment of the Evidence
title Placebo Response in Trials of Negative Symptoms in Schizophrenia: A Critical Reassessment of the Evidence
title_full Placebo Response in Trials of Negative Symptoms in Schizophrenia: A Critical Reassessment of the Evidence
title_fullStr Placebo Response in Trials of Negative Symptoms in Schizophrenia: A Critical Reassessment of the Evidence
title_full_unstemmed Placebo Response in Trials of Negative Symptoms in Schizophrenia: A Critical Reassessment of the Evidence
title_short Placebo Response in Trials of Negative Symptoms in Schizophrenia: A Critical Reassessment of the Evidence
title_sort placebo response in trials of negative symptoms in schizophrenia: a critical reassessment of the evidence
topic Regular Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9673255/
https://www.ncbi.nlm.nih.gov/pubmed/35713342
http://dx.doi.org/10.1093/schbul/sbac061
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