TY - JOUR
T1 - Heterogeneity in the pharmacodynamics of two long-acting methylphenidate formulations for children with attention-deficit/hyperactivity disorder: A growth mixture modelling analysis
AU - Sonuga-Barke, E.J.S.
AU - van Lier, P.A.C.
AU - Swanson, J.
AU - Coghill, D.
AU - Wigal, S.
AU - Vandenberghe, M.
AU - Hatch, S.
PY - 2008
Y1 - 2008
N2 - 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™/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. 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. © 2007 Steinkopff Verlag.
AB - 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™/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. 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. © 2007 Steinkopff Verlag.
U2 - 10.1007/s00787-007-0667-3
DO - 10.1007/s00787-007-0667-3
M3 - Article
VL - 17
SP - 254
EP - 254
JO - European Child and Adolescent Psychiatry
JF - European Child and Adolescent Psychiatry
SN - 1018-8827
ER -