Predicting Response to Atomoxetine and Methlyphenidate

预测对托莫西汀和哌醋甲酯的反应

• 批准号: 6878723
• 负责人: JEFFREY H NEWCORN
• 金额: $ 45.36万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-03 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6878723
• 关键词: adolescence (12-20); attention deficit disorder; behavioral /social science research tag; clinical research; clinical trials; cooperative study; drug screening /evaluation; human subject; human therapy evaluation; interview; mental disorder chemotherapy; methylphenidate; middle childhood (6-11); neurophysiology; neurotransmitter antagonist; patient oriented research; pharmacogenetics; psychopharmacologic agent

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.

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，代表了一个重大的公共卫生问题。大量的科学数据记录了心理兴奋剂在多动症症状和相关障碍中的强大效率[DJ1]和安全性。但是，响应也有很大的可变性，许多人报告的耐受性和可口性水平较低。此外，只有接受刺激治疗的人的一个亚组才能达到近似正常功能的反应。最近批准阿托米西汀（ATX）为治疗多动症提供了一种非刺激替代方案。 ATX在结构上与兴奋剂无关，并且似乎通过不同的机制起作用。因此，对于那些无法忍受兴奋剂或反应不足的人来说，ATX可能是一种有效的治疗方法，对两种治疗的反应者可能具有不同的临床和神经生物学特征。这项两次研究将使用随机的双盲，跨界设计，评估辅助哌醋甲酯（MPH）（MPH）和ATX对儿童和青少年治疗儿童和青少年在治疗儿童和青少年方面的相对功效，耐受性和可口性。迄今为止，尚无研究比较大量青少年的领先兴奋剂和非刺激治疗方法，使用每种治疗的最有效剂量，并评估同一患者对两种治疗方法的反应。我们将检验以下假设：MPH和ATX在320名儿童中具有相似的总体疗效，并且具有足够的统计能力可以检测到治疗之间的效果大小差异。我们将检查反应的“归一化”，以及更传统的结果，因为前者更紧密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，无论降低多动症症状的疗效群体差异如何，个体内部的反应和耐受性都将与不同的神经生物学特征有关。这些数据对于确定对两种治疗方法的最佳反应的个体中的这些因素，对患者，家庭和临床医生至关重要，并导致ADHD及其家人的疾病负担减轻疾病负担。