A Secondary Meta-Regression Analysis of the Relationship between Placebo and Nocebo Responses in ADHD Trials-Journal of Psychiatry and Brain Science-CSCIED科技核心评价数据库-手机版

A Secondary Meta-Regression Analysis of the Relationship between Placebo and Nocebo Responses in ADHD Trials

A Secondary Meta-Regression Analysis of the Relationship between Placebo and Nocebo Responses in ADHD Trials

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DOI	10.20900/jpbs.20250012
刊名	Journal of Psychiatry and Brain Science JPBS
年，卷(期)	2025, 10(5)
作者	Maggie Barcheni*,David Ramírez-Saco,Ruth Cunill,Magí Farré,Marc Saez,Xavier Castells,
作者单位	Department of Pharmacology Therapeutics and Toxicology, Universitat Autònoma de Barcelona, Bellaterra 08193, Spain ; Department of Clinical Pharmacology, Vall d’Hebron Barcelona Hospital Campus, Barcelona 08035, Spain ; Sant Joan de Deu-Numancia Health Park, Barcelona 08029, Spain ; Department of Clinical Pharmacology, Hospital Universitari Germans Trias i Pujol, Badalona 08916, Spain ; Center for Research in Health and Economics (CRES), Economy and Business Department, Universitat Pompeu Fabra, Barcelona 08005, Spain ; TransLab Research Group, Department of Medical Sciences, University of Girona, Girona 17004, Spain ;
摘要	Placebo and nocebo effects are psychological and physiological phenomena that significantly impact clinical trial outcomes, particularly in psychiatric disorders. While extensively studied individually, their interplay remains unexplored. This study investigates the relationship between placebo and nocebo responses in Attention Deficit Hyperactivity Disorder (ADHD) to improve the design and validity of Randomized Placebo-Controlled Clinical Trials (RPCCTs). This study is a secondary analysis of two previously published systematic reviews investigating placebo and nocebo responses in ADHD. A meta-regression analysis was conducted using data from 71 RPCCTs involving 6205 participants. Placebo response was measured as changes in ADHD symptom severity, while nocebo response was defined by the incidence of adverse events (AEs) in placebo groups. Multivariate analyses were used to explore the correlation between placebo and nocebo responses, adjusting for trial-level covariates. Placebo responses were positively associated with comorbidity as an inclusion criterion, psychotherapy, intention-to-treat analysis, and high risk of bias, and negatively associated with the number of study centers, use of a parallel design, and trials conducted in the U.S. Nocebo responses were positively associated with treatment naivety, treatment duration, proactive adverse event collection, and high risk of bias. The multivariate analysis showed no significant correlation between placebo and nocebo responses (coefficient = 0.0034, p-value = 0.8881) in ADHD trials. These findings challenge assumptions regarding the interdependence of placebo and nocebo responses and highlight the need for independent consideration of these phenomena in clinical trial design. Understanding these mechanisms can contribute to refining trial methodologies and optimizing therapeutic outcomes for ADHD. Further research is needed to explore whether this lack of correlation extends to other psychiatric disorders.
Abstract	Placebo and nocebo effects are psychological and physiological phenomena that significantly impact clinical trial outcomes, particularly in psychiatric disorders. While extensively studied individually, their interplay remains unexplored. This study investigates the relationship between placebo and nocebo responses in Attention Deficit Hyperactivity Disorder (ADHD) to improve the design and validity of Randomized Placebo-Controlled Clinical Trials (RPCCTs). This study is a secondary analysis of two previously published systematic reviews investigating placebo and nocebo responses in ADHD. A meta-regression analysis was conducted using data from 71 RPCCTs involving 6205 participants. Placebo response was measured as changes in ADHD symptom severity, while nocebo response was defined by the incidence of adverse events (AEs) in placebo groups. Multivariate analyses were used to explore the correlation between placebo and nocebo responses, adjusting for trial-level covariates. Placebo responses were positively associated with comorbidity as an inclusion criterion, psychotherapy, intention-to-treat analysis, and high risk of bias, and negatively associated with the number of study centers, use of a parallel design, and trials conducted in the U.S. Nocebo responses were positively associated with treatment naivety, treatment duration, proactive adverse event collection, and high risk of bias. The multivariate analysis showed no significant correlation between placebo and nocebo responses (coefficient = 0.0034, p-value = 0.8881) in ADHD trials. These findings challenge assumptions regarding the interdependence of placebo and nocebo responses and highlight the need for independent consideration of these phenomena in clinical trial design. Understanding these mechanisms can contribute to refining trial methodologies and optimizing therapeutic outcomes for ADHD. Further research is needed to explore whether this lack of correlation extends to other psychiatric disorders.
关键词	ADHD; placebo response; nocebo response; clinical trials; meta-regression; adverse events
KeyWord	ADHD; placebo response; nocebo response; clinical trials; meta-regression; adverse events
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Maggie Barcheni*,David Ramírez-Saco,Ruth Cunill,Magí Farré,Marc Saez,Xavier Castells. A Secondary Meta-Regression Analysis of the Relationship between Placebo and Nocebo Responses in ADHD Trials [J]. Journal of Psychiatry and Brain Science. 2025; 10; (5). - .

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