2/3-Atomoxetine Placebo and Parent Training in Autism

描述（由申请人提供）：自闭症谱系障碍（ASD）儿童注意力缺陷/多动（ADHD）的药理学随机临床试验相对较少。涉及兴奋剂药物的研究通常发现，与典型的ADHD儿童相比，反应率较差，无法忍受的副作用率较高。托莫西汀（Strattera）于2003年1月被FDA批准用于治疗ADHD。非兴奋剂，它抑制突触前去甲肾上腺素转运蛋白。只有四项研究（三项开放和一项小型双盲）在ASD儿童中检查了这种药物。行为治疗，如训练父母使用行为干预（PMT），也是典型发育儿童ADHD的标准治疗方法。虽然PMT也长期用于ASD，但很少在该人群中与精神药理学治疗相结合。该提案涉及4个目的：a）在156例ASD儿童中开展一项托莫西汀（ATX）与安慰剂在i）临床医生和家长评定的行为，ii）行为的直接观察，iii）注意力的认知/表现测量和iv）不良事件方面的双盲、安慰剂对照、10周平行组比较（ATX组78例，安慰剂组78例）; B）对156名ASD儿童进行为期10周的平行组比较，比较PMT与非PMT对行为依从性的影响（78例有PMT，78例无PMT）c）进行10周平行组比较，（ATX + PMT）vs.单药治疗（仅PMT）对156名ASD儿童的依从性措施;和d）通过一项针对应答者的开放标签6个月扩展试验，比较ATX和PMT的疗效、安全性和耐受性的长期维持。在前6周内，将根据获益和副作用滴定药物剂量（ATX上限为1.8 mg/kg/天）。PMT将是10个会议，1-1.5小时。每个，仿照RUPP自闭症网络PMT。数据分析将酌情利用2x2分析的力量。ASD儿童在药理学研究中被忽视，给医疗保健和教育系统带来了巨大的负担。这项试验有可能为一个相当大的ASD儿童亚组提供关于最佳治疗（心理社会和药理学）的答案，这些儿童经历了过度活动和注意力不集中的症状。

DESCRIPTION (provided by applicant): There have been relatively few randomized clinical trials of pharmacology for attention-deficit/hyperactivity (ADHD) in children with Autism Spectrum Disorders (ASD). Studies involving stimulant medications have generally found poorer response rates and higher rates of intolerable side effects than in typically developing children with ADHD. Atomoxetine (Strattera) was approved by the FDA in January 2003 for treatment of ADHD. A nonstimulant, it inhibits the presynaptic norephinephrine transporter. There have been only four studies (three open and one small double-blind) examining this medication in children with ASD. Behavioral treatments, such as training parents in the use of behavioral interventions (PMT), are also standard treatments for ADHD in typically developing children. While PMT also has long been used in ASD, it has rarely been studied in combination with psychopharmacologic treatment in this population. This proposal addresses four objectives: a) to conduct a double-blind, placebo-controlled, 10-week parallel-group comparison of atomoxetine (ATX) versus placebo on i) clinician- and parent-rated behavior, ii) direct observations of behavior, iii) cognitive/performance measures of attention, and iv) adverse events in 156 children with ASD (78 treated with ATX, 78 with placebo); b) to conduct a 10-week parallel-group comparison of PMT versus no-PMT on behavioral measures of compliance in 156 children with ASD (78 with PMT, 78 without PMT) c) to conduct a 10-week parallel-group comparison of combined (ATX plus PMT) vs. single treatment (PMT alone) on measures of compliance in 156 children with ASD; and d) to compare the long-term maintenance of efficacy, safety, and tolerability of ATX and PMT via an open-label 6-month extension trial of responders. Medication doses will be titrated against benefit and side effects over the first 6 weeks (ATX to a cap of 1.8 mg/kg/day). PMT will be 10 sessions, 1-1.5 hr. each, modeled on the RUPP Autism Network PMT. Data analyses will capitalize on the power of a 2 x 2 analysis where appropriate. Children with ASD have been neglected in pharmacological research, placing an enormous burden on health care and educational systems. This trial has the potential to provide answers regarding optimal treatment (both psychosocial and pharmacological) for a sizeable subgroup of children with ASD who experience symptoms of over activity and inattention.