Departments of Paediatrics and Psychiatry, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, 3010, Australia.
Division of Neuroscience, University of Dundee, Dundee, UK.
CNS Drugs. 2018 Jan;32(1):85-95. doi: 10.1007/s40263-017-0487-z.
SPD489-404 was the first 2-year safety study of lisdexamfetamine dimesylate in the treatment of attention-deficit/hyperactivity disorder in children and adolescents. In accordance with advice from the European Medicines Agency, assessment of cognitive function was a predefined safety outcome in SPD489-404.
The objective of this study was to assess cognitive function over 2 years in study SPD489-404, using the Cambridge Neuropsychological Test Automated Battery (CANTAB).
Participants aged 6-17 years received dose-optimised open-label lisdexamfetamine dimesylate (30, 50 or 70 mg/day) for 104 weeks. Cognition was assessed using four CANTAB tasks; Delayed Matching to Sample (DMS), Spatial Working Memory (SWM), Stop Signal Task (SST) and Reaction Time (RTI). Key and additional variables were pre-specified for each CANTAB task; groupwise mean percentage changes in key variables from baseline of > 5% were considered potentially clinically significant.
All 314 enrolled participants received lisdexamfetamine dimesylate and were included in the safety population, and 191 (60.8%) completed the study. No potentially clinically significant deteriorations from baseline were observed in any key CANTAB variable over the 2 years of the study. Based on predefined thresholds, potentially clinically significant improvements from baseline were observed at 6 months (DMS median reaction time, mean per cent change, - 6.6%; SWM total between-search errors, - 22.8%; SST stop signal reaction time, -18.9%), and at the last on-treatment assessment (DMS median reaction time, - 6.5%; SWM total between-search errors, - 32.6%; SST stop signal reaction time, - 25.7%).
Lisdexamfetamine dimesylate treatment for 2 years was not associated with deterioration of cognitive function in children and adolescents with attention-deficit/hyperactivity disorder. Although improvements in some cognitive measures were observed, lack of a control group makes interpretation of the findings difficult. Further studies of the impact of stimulants on cognition are required. CLINICALTRIALS.
NCT01328756.
SPD489-404 是 lisdexamfetamine 甲硫酸盐治疗儿童和青少年注意缺陷多动障碍的首次 2 年安全性研究。根据欧洲药品管理局的建议，认知功能评估是 SPD489-404 中的一个预先规定的安全性结局。
本研究旨在使用剑桥神经心理学测试自动电池（CANTAB）评估 SPD489-404 中 2 年的认知功能。
年龄在 6-17 岁的参与者接受了剂量优化的开放标签 lisdexamfetamine 甲硫酸盐（30、50 或 70mg/天）治疗 104 周。使用四个 CANTAB 任务评估认知功能；延迟匹配样本（DMS）、空间工作记忆（SWM）、停止信号任务（SST）和反应时间（RTI）。为每个 CANTAB 任务预先指定了关键和附加变量；与基线相比，关键变量的百分比变化>5%被认为具有潜在的临床意义。
所有 314 名入组的参与者均接受了 lisdexamfetamine 甲硫酸盐治疗，并被纳入安全性人群，其中 191 名（60.8%）完成了研究。在研究的 2 年内，任何关键 CANTAB 变量均未观察到与基线相比的潜在临床意义上的恶化。根据预先设定的阈值，在 6 个月时观察到与基线相比具有潜在临床意义的改善（DMS 中位反应时间，平均百分比变化，-6.6%；SWM 总搜索间错误，-22.8%；SST 停止信号反应时间，-18.9%），并且在最后一次治疗评估时（DMS 中位反应时间，-6.5%；SWM 总搜索间错误，-32.6%；SST 停止信号反应时间，-25.7%）。
在患有注意缺陷多动障碍的儿童和青少年中，接受 lisdexamfetamine 甲硫酸盐治疗 2 年不会导致认知功能恶化。尽管观察到一些认知测量指标的改善，但缺乏对照组使得对研究结果的解释变得困难。需要进一步研究兴奋剂对认知的影响。临床试验.gov 标识符：NCT01328756。
