A randomized, double-blind, placebo-controlled, parallel-group study of SLI381 (Adderall XR) in children with attention-deficit/hyperactivity disorder
A randomized, double-blind, placebo-controlled, parallel-group study of SLI381 (Adderall XR) in children with attention-deficit/hyperactivity disorder
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DOI：
10.1542/peds.110.2.258
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发表时间：
2002-08-01
期刊：
影响因子：
8
通讯作者：
Chandler, MC
中科院分区：
文献类型：
--
作者：
Biederman, J;Lopez, FA;Chandler, MC
Objective. SLI 381（Adderall XR）是Adderall的双组分缓释胶囊制剂，旨在产生持续一整天的治疗效果，每天早晨服用一次。本研究的主要目的是评估SLI 381与安慰剂相比在自然学校和家庭环境中治疗儿童注意力缺陷/多动障碍（ADHD）的疗效和安全性。第二个目标是评估响应的昼夜变化的基础上上午和下午的评估。在47个研究中心进行了一项多中心、随机、双盲、平行组、安慰剂对照试验。在任何先前的刺激性药物洗脱1周后，患者被随机分配接受安慰剂或SLI 381 10 mg、20 mg或30 mg的每日早晨单次剂量，持续3周。纳入了符合《精神疾病诊断和统计手册》第四版ADHD诊断标准的6至12岁（含）的参与者。主要疗效参数为Conners教师总体指数量表。次要疗效参数包括父母Conners总体指数量表、改善的临床总体不适量表和改善的父母总体评估。通过记录研究期间每次访视时的不良事件、实验室检查和生命体征来评估安全性。在筛选和研究结束时进行体格检查和心电图检查。584名儿童被随机分组，563名被纳入意向治疗人群，509名完成了整个研究。Conners教师全球指数量表和Conners父母全球指数量表评分的意向治疗分析显示，与安慰剂相比，所有活性治疗组的上午、下午和下午晚些时候的行为均有显著改善。所有活性药物治疗组均显示行为较基线显著剂量相关改善。用于改善的临床总体不适量表和用于改善的父母总体评估均显示在治疗结束时所有剂量的SLI 381均上级安慰剂，并且均证实了改善与SLI 381剂量之间的剂量-反应关系。自发报告的不良事件的发生率较低，活性治疗组和安慰剂组相似。SLI 381对所有疗效指标产生了一致的、剂量相关的改善。SLI 381制剂的缓释性质通过教师的下午评估以及家长的下午和下午晚些时候的评估的持续显著改善来显示。SLI 381的时间进程和治疗效果表明，这种药物是一种有效的治疗ADHD儿童每日一次。
Objective. SLI381 (Adderall XR) is a 2-component extended-release capsule formulation of Adderall designed to produce a therapeutic effect that lasts throughout the day with 1 morning dose. The primary objective of this study was to assess the efficacy and safety of SLI381 compared with placebo in the treatment of attention-deficit/hyperactivity disorder (ADHD) in children in a naturalistic school and home setting. A secondary objective was to assess the diurnal variation in responses based on morning and afternoon assessments.Methods. A multicenter, randomized, double-blind, parallel-group, placebo-controlled trial was conducted at 47 sites. After a 1-week washout of any previous stimulant medication, patients were randomized to receive single-daily morning doses of placebo or SLI381 10 mg, 20 mg, or 30 mg for 3 weeks. Participants aged 6 to 12 years inclusive who satisfied Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria diagnosis of ADHD were included. The primary efficacy parameter was the Conners Global Index Scale for Teachers. Secondary efficacy parameters included the Conners Global Index Scale for Parents, the Clinical Global Impressions Scale for improvement, and the Parent Global Assessment for improvement. Safety was assessed by recording adverse events, laboratory tests, and vital signs at each visit during the study. Physical examinations and electrocardiograms were performed at the screening and the end of the study.Results. Five hundred eighty-four children were randomized, 563 were included in the intent-to-treat population, and 509 completed the entire study. Intention-to-treat analysis of Conners Global Index Scale for Teachers and Conners Global Index Scale for Parents scores revealed significant improvement in morning, afternoon, and late afternoon behavior for all active treatment groups versus placebo. All active treatment groups showed significant dose-related improvement in behavior from baseline. Both the Clinical Global Impressions Scale for improvement and Parent Global Assessment for improvement showed all doses of SLI381 to be superior to placebo at treatment end and both confirmed the dose-response relationship between improvement and the SLI381 dose. The incidence of spontaneously reported adverse events was low and similar for active treatments and placebo.Conclusions. SLI381 produced consistent, dose-related improvements on all measures of efficacy. The extended-release nature of the SLI381 formulation was shown by continued, significant improvement in afternoon assessments by teachers and afternoon and late afternoon assessments by parents. The time course and therapeutic effects of SLI381 suggests that this medication is an efficacious once-daily treatment for children with ADHD.