Sonuga-Barke Edmund J S, Van Lier Pol, Swanson James M, Coghill David, Wigal Sharon, Vandenberghe Mieke, Hatch Simon
School of Psychology, Institute for Disorders of Impulse and Attention, University of Southampton, Southampton, UK.
Eur Child Adolesc Psychiatry. 2008 Jun;17(4):245-54. doi: 10.1007/s00787-007-0667-3.
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.
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).
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.
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.
运用生长混合模型（GMM）来识别注意力缺陷多动障碍（ADHD）儿童的亚组，这些亚组儿童在实验室课堂环境中对缓释哌甲酯的药效学特征不同。
对COMACS研究（模拟课堂环境中哌甲酯的比较）的数据进行GMM分析：这是一项大型（n = 184）安慰剂对照交叉研究，比较了实验室学校方案中的三种治疗条件（进行1.5小时的注意力和行为评估循环）。将两种口服、每日一次的哌甲酯（MPH）生物等效制剂[Metadate CD/Equasym XL（MCD-EQXL）和Concerta XL（CON）]与安慰剂（PLA）进行比较。
在安慰剂条件下识别出了三类具有不同严重程度特征的儿童。对于MCD-EQXL和CON，儿童在安慰剂条件下症状越严重，对药物的反应就越好。然而，这两种制剂在不同类别中产生了不同的生长曲线，CON在所有三类中基本呈现平缓曲线（即不受安慰剂严重程度影响），而MCD-EQXL在最严重的两类中，给药后症状立即明显下降，相比最不严重的类别。对速释（IR）成分匹配的每日剂量进行比较解释了这种差异。
结果表明ADHD儿童对MPH反应的药效学存在相当大的异质性。当比较两种制剂在近乎相等的生物等效每日剂量下的治疗反应时，最严重类别的儿童出现了明显差异，MCD-EQXL呈现出强烈的曲线轨迹，这与更大的IR成分有关。
