Patterns of Response to Methylphenidate Administration in Children with ADHD: A Personalized Medicine Approach through Clustering Analysis

Abstract

Individual responses to methylphenidate (MPH) can significantly differ in children with attention-deficit/hyperactivity disorder (ADHD) in terms of the extent of clinical amelioration, optimal dosage needed, possible side effects, and short- and long-term duration of the benefits. In the present repeated-measures observational study, we undertook a proof-of-concept study to determine whether clustering analysis could be useful to characterize different clusters of responses to MPH in children with ADHD. We recruited 33 children with ADHD who underwent a comprehensive clinical, cognitive, and neurophysiological assessment before and after one month of MPH treatment. Symptomatology changes were assessed by parents and clinicians. The neuropsychological measures used comprised pen-and-paper and computerized tasks. Functional near-infrared spectroscopy was used to measure cortical hemodynamic activation during an attentional task. We developed an unsupervised machine learning algorithm to characterize the possible clusters of responses to MPH in our multimodal data. A symptomatology improvement was observed for both clinical and neuropsychological measures. Our model identified distinct clusters of amelioration that were related to symptom severity and visual-attentional performances. The present findings provide preliminary evidence that clustering analysis can potentially be useful in identifying different responses to MPH in children with ADHD, highlighting the importance of a personalized medicine approach within the clinical framework.

Using fNIRS to evaluate ADHD medication effects on neuronal activity: A systematic literature review

“…Only one study ( Grazioli et al, 2021 ) did not find increased activation in the targeted brain regions post medication. In this study, Grazioli et al (2021) failed to demonstrate brain activation in the prefrontal region following methylphenidate administration and they reasoned that fNIRS may not have been sensitive enough to identify changes that may have occurred subcortically.…”

“…All six studies that looked at the long-term response to medication took two fNIRS measurements at intervals ranging from 1 month ( Grazioli et al, 2021 ) up to a maximum of 1 year ( Araki et al, 2015 ), while studies exploring both the immediate- and long-term effects of medication took three or more measurements. Wigal et al (2012) and Li et al (2022) conducted fNIRS measurements three times and Ishii-Takahashi et al (2015) conducted between four and five fNIRS measurements depending on whether participants were or were not medication-naïve at the start of the study.…”

“…One study Grazioli et al (2021) did not report the specific dosages and stated that doses were adjusted based on treatment response and tolerability and were maintained until the second evaluation of the study after the second week.…”

Functional near-infrared spectroscopy in pediatric clinical research: Different pathophysiologies and promising clinical applications

“…Interestingly, four articles (4/21) aimed to identify fNIRS markers predictive of the clinical response to medication in children with ADHD. In 2021, Grazioli et al 88 suggesting that such a model could eventually help to predict how a patient will respond to a pharmaceutical treatment. However, larger coverage (not only including the prefrontal and frontal areas) would again be more informative.…”

Assessing therapeutic response to methylphenidate among children and adolescents with Attention-Deficit Hyperactivity Disorder: Narrative Review of its effects on emotional regulation, executive functions, and quality of life

“…Moreover, some studies suggest that around 25% to 35% don't respond to methylphenidate treatment at all (25-35%, Arnett et al, 2022;Stein et al, 2011). Increased research efforts are being made to understand the possible behavioral and biological specificities that are linked to MPH efficacy (Grazioli et al, 2021). But, as of yet, optimal therapeutic response to pharmacological treatments in children, adolescents and adults is still a matter of trial and error (Cortese 2020;Huss et al, 2017;Jaeschke et al, 2021).…”