Nocebo response in attention-deficit/hyperactivity disorder:meta-analysis and meta-regression of 105 randomized

Abstract

BACKGROUND Nocebo response (worsening of clinical symptoms or the experiencing of treatment-emergent adverse effects when administering an inert substance) is relevant in both clinical practice and research due to role played in withdrawals and lack of therapeutic adherence. Nocebo response in attention deficit hyperactivity disorder (ADHD) as a primary objective, the effect of its covariates and its relationship with drug safety have not been studied before. OBJECTIVES To determine nocebo response in ADHD, identify covariates modifying nocebo response, and study the relationship between nocebo response and drug safety. METHODS 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. CONCLUSIONS Nocebo response in ADHD RCTs is remarkable, showing a positive relationship with drug response, and a negative relationship with drug safety