Methylphenidate dose-response in children with ADHD: Evidence from a double-blind, randomized placebo-controlled titration trial

Background: Methylphenidate (MPH) is highly efficacious in reducing symptoms of attention-deficit/hyperactivity disorder (ADHD) in children. Generally higher doses are found to result in better symptom control, however, it remains unclear whether this pattern can be observed at the individual level, given the large heterogeneity in individual dose-response relationships and observed placebo responses. Methods A double-blind, randomized, placebo-controlled cross-over trial was used to compare weekly treatment with placebo and 5, 10, 15 and 20 mg of MPH twice daily on parent and teacher ratings of child ADHD symptoms and side effects. Participants were 5–13 year old children with a DSM-5 diagnosis of ADHD (N = 45). MPH response was assessed at group and individual levels and predictors of individual dose-response curves were examined. Results Mixed model analysis showed positive linear dose-response curves at group level for parent and teacher rated ADHD symptoms and parent rated side effects, but not for teacher rated side effects. Teachers reported all dosages to improve ADHD symptoms compared to placebo, while parents only reported > 5 mg/dose as effective. At the individual level, most (73–88%) children showed positive linear dose-response curves. Higher severity of hyperactive-impulsive symptoms and lower internalizing problems, lower weight, younger age and more positive opinions towards diagnosis and medication partly predicted steeper linear individual dose-response curves. Conclusions Our study confirms that higher doses of MPH yield greater symptom control at a group level. However, large interindividual variation in the dose-response relationship was found and higher doses did not lead to greater symptom improvement for all children.