Measuring and Predicting Responses to ATX and MPH

描述(申请人提供)：ADHD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管理ADHD症状和相关损害方面的强大疗效和安全性。然而，反应也有相当大的变异性，许多人报告说耐受性和适口性水平较低。此外，在接受兴奋剂治疗的患者中，只有一小部分人的反应接近正常功能。最近批准的阿托莫西汀(ATX)为治疗ADHD提供了一种非刺激性替代药物。ATX在结构上与兴奋剂无关，似乎通过不同的机制发挥作用。因此，对于那些不能耐受兴奋剂或反应不足的人，ATX可能是一种有效的治疗方法，而对这两种治疗方法的应答者可能具有不同的临床和神经生物学特征。这项为期两个地点的研究将采用随机、双盲、交叉设计的方法，评估醋酸康可达(MPH)和ATX治疗儿童和青少年ADHD的相对疗效、耐受性和适口性。到目前为止，还没有研究在大量年轻人中比较主要的兴奋剂和非兴奋剂治疗，对每种治疗使用最有效的剂量，并评估同一个体对这两种治疗的反应。我们将检验这一假设，即MPH和ATX在320名儿童中具有类似的总体疗效，并具有足够的统计能力来检测两种治疗之间即使是微小的效果大小差异。我们将研究反应的“正常化”，以及更传统的结果，因为前者更能反映理想的治疗终点。此外，我们还将评估基因的潜在调节作用。我们假设，无论组内ADHD症状缓解效果的差异如何，个体内都会有不同的反应和耐受性，这将与不同的神经生物学特征有关。这些数据将对患者、家庭和临床医生至关重要，有助于确定个人内部预测两种治疗方案的最佳反应的因素，并有助于减轻患有ADHD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.