Measuring and Predicting Responses to ATX and MPH

描述（由申请人提供）：多动症是儿童和青少年最常见的疾病之一，是一个重大的公共卫生问题。大量的科学数据证明了精神兴奋剂在治疗多​​动症症状和相关障碍方面的强大功效和安全性。然而，反应也存在很大差异，许多人报告耐受性和适口性较低。此外，只有一小部分接受兴奋剂治疗的人能达到接近正常功能的反应。最近批准的托莫西汀 (ATX) 为治疗多动症提供了一种非兴奋剂替代方案。 ATX 在结构上与兴奋剂无关，并且似乎通过不同的机制发挥作用。因此，ATX对于那些不能耐受兴奋剂或反应不足的人来说可能是一种有效的治疗方法，并且对两种治疗方法的反应者可能具有不同的临床和神经生物学特征。这项两中心研究将采用随机、双盲、交叉设计，评估 Concerta 哌甲酯 (MPH) 和 ATX 在治疗患有 ADHD 的儿童和青少年中的相对疗效、耐受性和适口性。迄今为止，还没有研究对大量青少年使用主要的兴奋剂和非兴奋剂治疗进行比较，对每种治疗使用最有效的剂量，并评估同一个人对两种治疗的反应。我们将检验 MPH 和 ATX 在 320 名儿童中具有相似总体疗效的假设，并具有足够的统计能力来检测治疗之间即使很小的效应大小差异。我们将检查反应的“正常化”以及更传统的结果，因为前者更接近地反映了所需的治疗终点。我们还将评估基因型的潜在调节作用。我们假设，无论 ADHD 症状减轻功效的群体差异如何，个体内部都会存在不同的反应和耐受性，这与不同的神经生物学特征相关。这些数据对于患者、家庭和临床医生来说至关重要，可以确定个体内部的因素，预测对两种治疗的最佳反应，并减少患有多动症的青少年及其家人的疾病负担。

DESCRIPTION (provided by applicant): ADHD is one of the most frequently occurring disorders of children and adolescents, and represents a significant public health problem. A plethora of scientific data documents the robust efficacy [dj1]and safety of psycho stimulants for the management of ADHD symptoms and associated impairments. However, there is also considerable variability in response, with many individuals reporting lower levels of tolerability and palatability. Moreover, only a subgroup of those receiving stimulant treatments achieves a response that approximates normal functioning. The recent approval of atomoxetine (ATX) offers a non-stimulant alternative for the treatment of ADHD. ATX is structurally unrelated to the stimulants and appears to work via a different mechanism. Thus, ATX may be an effective treatment for those who cannot tolerate stimulants or who have an inadequate response, and responders to the two treatments may have different clinical and neurobiological characteristics. This two-site study will evaluate the relative efficacy, tolerability and palatability of Concerta methylphenidate (MPH) and ATX in the treatment of children and adolescents with ADHD, using a randomized, double blind, crossover design. To date, no study has compared the leading stimulant and non-stimulant treatments in large numbers of youth, using the most effective doses for each treatment, and evaluating response to both treatments in the same individuals. We will test the hypothesis that MPH and ATX have similar overall efficacy in 320 children, with sufficient statistical power to detect even a small effect size difference between the treatments. We will examine "normalization" of response, as well as more traditional outcomes, because the former more closely reflects the desired endpoint of treatment. We will additionally evaluate the potential moderating effects of genotype. We hypothesize that regardless of group differences in efficacy in ADHD symptom reduction, there will be differential response and tolerability within individuals, which will be associated with distinct neurobiological characteristics. These data will be vitally important to patients, families, and clinicians in identifying those factors within individuals that predict optimal response to the two treatments, and lead to a reduction in burden of illness for youth with ADHD and their families.