Placebo Response and Its Predictors in Attention Deficit Hyperactivity Disorder: A Meta-Analysis and Comparison of Meta-Regression and MetaForest.
Por:
Castells X, Saez M, Barcheni M, Cunill R, Serrano D, López B and van Lissa C
Publicada:
12 ene 2022
Ahead of Print:
6 ago 2021
Resumen:
BACKGROUND: High placebo response in attention deficit hyperactivity disorder (ADHD) can reduce medication-placebo differences, jeopardizing the development of new medicines. This research aims to (1) determine placebo response in ADHD, (2) compare the accuracy of meta-regression and MetaForest in predicting placebo response, and (3) determine the covariates associated with placebo response. METHODS: A systematic review with meta-analysis of randomized, placebo-controlled clinical trial investigating pharmacological interventions for ADHD was performed. Placebo response was defined as the change from baseline in ADHD symptom severity assessed according to the 18-item, clinician-rated, DSM-based rating scale. The effect of study design-, intervention-, and patient-related covariates in predicting placebo response was studied by means of meta-regression and MetaForest. RESULTS: Ninety-four studies including 6614 patients randomized to placebo were analyzed. Overall, placebo response was -8.9 points, representing a 23.1% reduction in the severity of ADHD symptoms. Cross-validated accuracy metrics for meta-regression were R2 = 0.0012 and root mean squared error = 3.3219 for meta-regression and 0.0382 and 3.2599 for MetaForest. Placebo response among ADHD patients increased by 63% between 2001 and 2020 and was larger in the United States than in other regions of the world. CONCLUSIONS: Strong placebo response was found in ADHD patients. Both meta-regression and MetaForest showed poor performance in predicting placebo response. ADHD symptom improvement with placebo has markedly increased over the last 2 decades and is greater in the United States than the rest of the world.
Filiaciones:
Castells X:
TransLab research group, Department of Medical Sciences, Universitat de Girona, Girona, Spain
Saez M:
Research Group on Statistics, Econometrics and Health (GRECS), Universitat de Girona, Girona, Spain
Centre for Biomedical Research Network in Epidemiology and Public Health (CIBERESP), Madrid, Spain
Barcheni M:
Pharmacology, toxicology and therapeutics department. Universitat Autònoma de Barcelona, Barcelona, Spain
Cunill R:
Parc Sanitari Sant Joan de Déu-Numància, Parc Sanitari Sant Joan de Déu, Barcelona, Spain
Serrano D:
Institut d'Assistència Sanitària, Girona, Spain
López B:
Control and Intelligent Systems Engineering Research Group, Electrical, Electronic and Automatic Engineering Department, Universitat de Girona, Girona, Spain
van Lissa C:
Department of Methodology and Statistics, Universiteit Utrecht, The Netherlands
Green Published, gold
|