Heterogeneity in the pharmacodynamics of two long-acting methylphenidate formulations for children with attention deficit/hyperactivity disorder. A growth mixture modelling analysis.
OBJECTIVE
To use growth mixture modelling (GMM) to identify subgroups of children with attention deficit hyperactive disorder (ADHD) who have different pharmacodynamic profiles in response to extended release methylphenidate as assessed in a laboratory classroom setting.


METHODS
GMM analysis was performed on data from the COMACS study (Comparison of Methylphenidates in the Analog Classroom Setting): a large (n = 184) placebo-controlled cross-over study comparing three treatment conditions in the Laboratory School Protocol (with a 1.5-h cycle of attention and deportment assessments). Two orally administered, once-daily methylphenidate (MPH) bioequivalent formulations [Metadate CD/Equasym XL (MCD-EQXL) and Concerta XL (CON)] were compared with placebo (PLA).


RESULTS
Three classes of children with distinct severity profiles in the PLA condition were identified. For both MCD-EQXL and CON, the more severe their PLA symptoms the better, the children's response. However, the formulations produced different growth curves by class, with CON having essentially a flat profile for all three classes (i.e. no effect of PLA severity) and MCD-EQXL showing a marked decline in symptoms immediately post-dosing in the two most severe classes compared with the least severe. Comparison of daily doses matched for immediate-release (IR) components accounted for this difference.


CONCLUSIONS
The results suggest considerable heterogeneity in the pharmacodynamics of MPH response by children with ADHD. When treatment response for near-equal, bioequivalent daily doses the two formulations was compared, marked differences were seen for children in the most severe classes with a strong curvilinear trajectory for MCD-EQXL related to the greater IR component.
Sonuga-Barke
Edmund J S
EJ
School of Psychology, Institute for Disorders of Impulse and Attention, University of Southampton, Southampton, UK. ejb3@soton.ac.uk
Van Lier
Pol
P
Swanson
James M
JM
Coghill
David
D
Wigal
Sharon
S
Vandenberghe
Mieke
M
Hatch
Simon
S
D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D002648:Child; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use*; D015233:Models, Statistical; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D015588:Observer Variation; D010919:Placebos; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; D010919:Placebos; D008774:Methylphenidate