Nocebo Response in Attention Deficit Hyperactivity Disorder: Meta-Analysis and Meta-Regression of 105 Randomized Clinical Trials

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.