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Randomized Controlled Trial
. 2024 Feb;33(2):495-504.
doi: 10.1007/s00787-023-02176-x. Epub 2023 Mar 2.

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

Karen Vertessen  1   2   3 , Marjolein Luman  4   5 , James M Swanson  6 , Marco Bottelier  7 , Reino Stoffelsen  5 , Pierre Bet  8 , Annemiek Wisse  9 , Jos W R Twisk  10 , Jaap Oosterlaan  4   11
Affiliations
Randomized Controlled Trial

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

Karen Vertessen et al. Eur Child Adolesc Psychiatry. 2024 Feb.

Abstract

Methylphenidate (MPH) is highly efficacious in reducing symptoms of attention-deficit/hyperactivity disorder (ADHD) in children. Generally increased 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. 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. 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, but not all, 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. Our study confirms that increased doses of MPH yield greater symptom control at a group level. However, large interindividual variation in the dose-response relationship was found and increased doses did not lead to greater symptom improvement for all children. This trial was registered in the Netherlands trial register (# NL8121).

Keywords: Attention-deficit; Dose–response; Hyperactivity disorder; Methylphenidate; Placebo-response.

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Conflict of interest statement

The authors declare no competing interests.

Karen Vertessen has been involved in a clinical trial sponsored by Takeda. The other authors have no conflicts of interest relevant to this article to disclose.

Figures

Fig. 1
Fig. 1
Histogram of regression coefficients obtained from the individual linear dose–response curves. The left arrows represent the percentage of children with negative dose–response curves, while the right arrows represent the percentage of children with positive dose–response curves
See this image and copyright information in PMC

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