Placebo Response and Its Predictors in Attention Deficit Hyperactivity Disorder : A Meta-Analysis and Comparison of Meta-Regression and MetaForest
Castells Cervelló, Xavier (Universitat de Girona)
Saez, Marc (Centro de Investigación Biomédica en Red de Cáncer)
Barcheni, Maghie (Universitat Autònoma de Barcelona)
Cunill, Ruth (Hospital Sant Joan de Déu)
Serrano Sarbosa, Domènec (Universitat de Girona)
López, Beatriz (Universitat de Girona)
van Lissa, Caspar J. (Universiteit Utrecht)

Data:	2022
Resum:	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 R = 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.
Ajuts:	Instituto de Salud Carlos III PI19/00375
Nota:	Altres ajuts: NWO Veni grant (NWO grant no. VI.Veni.191G.090)
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Attention Deficit Hyperactivity Disorder ; Machine learning ; MetaForest ; Meta-analysis ; Meta-regression ; Placebo response
Publicat a:	International journal of neuropsychopharmacology, Vol. 25 Núm. 1 (January 2022) , p. 26-35, ISSN 1469-5111

DOI: 10.1093/ijnp/pyab054
PMID: 34355753

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