An Evaluation Approach for the Performance of Dosing Regimens in Attention-Deficit/Hyperactivity Disorder Treatment

Abstract

Objective: Stimulant medications, with methylphenidate as the main agent, are the most prescribed for the treatment of attention-deficit/hyperactivity disorder. Nevertheless, real challenges still remain for clinicians concerned with adaptation of the therapeutic regimens, in terms of doses and timing, to children's daily activities. The aim of this study was to optimize short-acting methylphenidate regimens according to specific children's needs by evaluating the performance of a particular regimen through a web-based application. Methods: In this article, accounting for day-to-day children's activities and using up-to-date pharmacokinetic knowledge of methylphenidate, we propose a computational approach for the identification of the most suitable dosing regimens of immediate-release formulations of methylphenidate based on constraints on drug concentration and time frame of activities, defined through therapeutic boxes. To assess the performance of these regimens, time-and concentration-based therapeutic indicators, as well as a roller coaster effect, are proposed. Results: A web-based interface that can serve as an educational tool for clinicians and patients has been developed based on the proposed approach for the evaluation of dosing regimens. Comparison of those optimal regimens identified by our method with the well-accepted regimens defined in the NIMH Collaborative Multisite Multimodal Treatment study of Children with attention-deficit/hyperactivity disorder indicates that there is still room for improvement in the current practice especially for the last dose administration to avoid side effects such as sleep disturbance. Conclusion: The developed approach and its associated web-based interface provide an efficient way to evaluate and adapt the methylphenidate regimens to children's daily activities. In addition, this approach could be used as proof of concept to further implement combination of short-and long-acting methylphenidate.

The Decrease in Human Endogenous Retrovirus-H Activity Runs in Parallel with Improvement in ADHD Symptoms in Patients Undergoing Methylphenidate Therapy

“…The intensity and frequency of the core symptoms of ADHD were assessed with the long version of the Conners’ Parents Rating Scale-Revised questionnaire (CPRS-R). The CPRS-R was conducted at eight and 24 weeks after MPH treatment as any clinical response cannot be detected before that time [ 55 , 56 ]. Four clinical variables were considered: the Conners’ parent oppositional (CP-O), the Conners’ parent inattention (CP-I), the parent hyperactivity/impulsivity (CP-H), and the Conners’ parent ADHD-Index (CP-AI).…”

“…Herein, we analyzed the time-course of HERV-H transcriptional activity in PBMCs from ADHD patients after 1, 8, and 24 weeks of MPH therapy, demonstrating that the expression of HERV-H significantly decreased after only one week. Interestingly, at this time of observation, no significant improvement of clinical symptoms by MPH treatment can be achieved [ 55 , 56 ]. Subsequent to the fast downregulation of HERV-H expression, a further decreasing trend was confirmed throughout the 24 weeks of therapy.…”