2/3-Atomoxetine Placebo and Parent Training in Autism

描述(由申请人提供)：针对自闭症谱系障碍(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，与典型的发展中的ADHD儿童相比，反应率较低，无法忍受的副作用发生率较高。阿托莫西汀(Strattera)于2003年1月被FDA批准用于治疗ADHD。作为一种非兴奋剂，它抑制突触前去甲肾上腺素转运体。只有四项研究(三项开放和一项小型双盲)研究了这种药物在自闭症儿童中的应用。行为治疗，如培训父母使用行为干预(PMT)，也是典型发育中儿童ADHD的标准治疗方法。虽然PMT也长期用于ASD，但很少有人将其与精神药物治疗结合在这一人群中进行研究。这项建议涉及四个目标：a)对阿托莫西汀(ATX)和安慰剂进行为期10周的双盲、安慰剂对照平行小组比较：i)临床医生和父母评估的行为，ii)行为的直接观察，iii)注意力的认知/表现测量，以及iv)156名自闭症儿童的不良事件(78人服用ATX，78人服用安慰剂)；B)对156名ASD儿童(78名患有PMT，78名不接受PMT)进行为期10周的PMT与非PMT的行为依从性测量的平行分组比较；c)对156名ASD儿童的遵从性测量进行为期10周的联合(ATX+PMT)与单一治疗(PMT)的平行分组比较；以及d)通过一项为期6个月的开放标签延长试验，比较ATX和PMT对疗效、安全性和耐受性的长期维持。药物剂量将在前6周根据益处和副作用进行滴定(ATX上限为1.8毫克/公斤/天)。PMT将为10节课，1-1.5小时。每一个，都是以RUPP自闭症网络PMT为模型的。数据分析将在适当的情况下利用2x2分析的力量。患有自闭症的儿童在药理学研究中一直被忽视，给卫生保健和教育系统带来了巨大的负担。这项试验有可能为经历过度活动和注意力不集中症状的相当大一部分自闭症儿童提供关于最佳治疗(心理和药物治疗)的答案。

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.