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


CONCLUSIONS
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.
1 Faculté de Pharmacie, Université de Montréal , Montréal, Canada .
Guillaume
G
Bonnefois
2 Children's Hospital of Eastern Ontario (CHEO) , Ottawa, Canada .|3 Department of Psychiatry, University of Ottawa , Ottawa, Canada .|4 Département de Psychiatrie, Université de Montréal , Montréal, Canada .
Philippe
P
Robaey
5 inVentiv Health Clinical , Montréal, Canada .
Olivier
O
Barrière
1 Faculté de Pharmacie, Université de Montréal , Montréal, Canada .|6 Centre de Recherches Mathématiques, Université de Montréal , Montréal, Canada .
Jun
J
Li
1 Faculté de Pharmacie, Université de Montréal , Montréal, Canada .|6 Centre de Recherches Mathématiques, Université de Montréal , Montréal, Canada .
Fahima
F
Nekka
D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002648:Child; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015233:Models, Statistical
D000697:Central Nervous System Stimulants; D008774:Methylphenidate
dose adaptation; eHealth; methylphenidate; population pharmacokinetics; precision medicine; web-based application