Heterogeneity in the pharmacodynamics of two long-acting methylphenidate formulations for children with attention deficit/hyperactivity disorder - A growth mixture modelling analysis

Edmund J. S. Sonuga-Barke, Pol Van Lier, James M. Swanson, David Coghill, Sharon Wigal, Mieke Vandenberghe, Simon Hatch

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    Objectives 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 (TM)/Equasym (TM) 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. Conclusion 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.

    Original languageEnglish
    Pages (from-to)245-254
    Number of pages10
    JournalEuropean Child & Adolescent Psychiatry
    Issue number4
    Publication statusPublished - Jun 2008


    • pharmacodynamics
    • pharmacokinetics
    • attention deficit/hyperactivity disorder
    • stimulant medication
    • methylphenidate
    • COMACS
    • growth mixture models
    • ADHD
    • MTA

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