Inattention deficit hyperactivity disorder (ADHD), a high placebo response can minimize medication–placebo differences, compromising the development of novel medications. For a study, researchers sought to (1) assess placebo response in ADHD, (2) compare the accuracy of meta-regression and MetaForest in predicting placebo response, and (3) identify factors related to placebo response. A meta-analysis of randomized, placebo-controlled clinical trials examining pharmaceutical treatments for ADHD was carried out. The placebo response was defined as the change from baseline in the severity of ADHD symptoms as measured by the 18-item, clinician-rated, DSM-based rating scale. Meta-regression and MetaForest were used to investigate the influence of trial design, intervention, and patient-related factors on placebo response. 

A total of 94 trials with a total of 6614 individuals randomized to placebo were examined. Overall, the placebo response was 8.9 points, corresponding to a 23.1% reduction in the severity of ADHD symptoms. For meta-regression, the cross-validated accuracy metrics were R^2=0.0012 and root means squared error=3.3219, whereas, for MetaForest, they were 0.0382 and 3.2599. Placebo response grew by 63% among V with ADHD between 2001 and 2020 and was greater in the United States than in other parts of the world.

Patients with ADHD showed a strong placebo response. Meta-regression and MetaForest both performed poorly in predicting placebo response. ADHD symptom improvement with placebo has grown significantly over the previous two decades, with the United States outperforming the rest of the globe.

Reference:academic.oup.com/ijnp/article/25/1/26/6342746