Nocebo Response in Attention Deficit Hyperactivity Disorder

Meta-Analysis and Meta-Regression of 105 Randomized Clinical Trials

  • Ramírez-Saco, David
  • Barcheni, Maghie
  • Cunill, Ruth
  • Sáez, Marc
  • Farré, Magí
  • Castells, Xavier

  • 1School of Medicine, Universitat de Girona, Girona, Spain

    2Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Barcelona, Spain

    3Parc Sanitari Sant Joan de Déu, Barcelona, Spain

    4Sant Joan de Déu, Institut de Recerca, Sant Boi de Llobregat, Barcelona, Spain

    5Research Group on Statistics, Econometrics and Health (GRECS), Economy Department, Universitat de Girona, Girona, Spain

    6Consortium for Biomedical Research Center of Epidemiology and Public Health (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain

    7Center for Research in Health and Economics (CRES), Economy and Business Department, Universitat Pompeu Fabra, Barcelona, Spain

    8Department of Clinical Pharmacology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain

    9TransLab research group, Department of Medical Sciences, Universitat de Girona, Girona, Spain

David Ramírez-Saco, School of Medicine, University of Girona, C/ Emili Grahit, 77, esc. B, 2n, Girona 17003, Spain. Email: [email protected]

Xavier Castells, Department of Medical Sciences, University of Girona, C/ Emili Grahit, 77, esc. B, 2n, Girona 17003, Spain. Email: [email protected]

Journal of Attention Disorders 26(11):p 1412-1421, September 2022. | DOI: 10.1177/10870547221075845

Objective:

To determine nocebo response in ADHD, identify covariates modifying nocebo response, and study the relationship between nocebo response and drug safety.

Method:

Systematic review of randomized, double-blind, placebo-controlled clinical trials (RCT) investigating the efficacy and safety of pharmacological interventions for ADHD patients. The influence of covariates was studied using meta-regression.

Results:

A total of 105 studies with 8,743 patients in placebo arms were included. Slightly over half (55.5%) of the patients experienced adverse events (AE) while receiving placebo. Nocebo response was associated positively with age, treatment length and method for collecting AEs. Studies with the largest nocebo response showcased the greatest drug response and the best outcome for drug safety.

Conclusion:

Nocebo response in ADHD RCTs is remarkable, showing a positive relationship with drug response, and a negative relationship with drug safety.

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