Jin Ling, Xu Wen, Krefetz David, Gruener Daniel, Kielbasa William, Tauscher-Wisniewski Sitra, Allen Albert J
Lilly Research Laboratory, Eli Lilly and Company, Indianapolis, IN, USA.
J Child Adolesc Psychopharmacol. 2013 Apr;23(3):200-7. doi: 10.1089/cap.2012.0016.
The purpose of this study was to assess the clinical outcomes from an open label study of edivoxetine, a selective norepinephrine reuptake inhibitor, in pediatric patients with attention-deficit/hyperactivity disorder (ADHD).
This was a multi-cohort open-label study of edivoxetine consisting of a single-dose administration period (Part 1) and an open-label once daily (QD) dose long-term period (Part 2). Adolescents ages 12-17 years and children ages 6-11 years were enrolled in Part 1 and continued to Part 2 where they received 0.05 to 0.3 mg/kg edivoxetine QD for ≤12 months. Safety was assessed by adverse events, vital signs, weight, electrocardiograms, and laboratory tests. In Part 2, Attention-Deficit/Hyperactivity Disorder Rating Scale-Version IV-Parent Reported: Investigator Scored (ADHDRS-IV) and Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) scores were determined.
Fifty-three patients enrolled in Part 1, and 49 continued to Part 2 with a mean exposure duration of 22 weeks. The 31 patients completing Part 2 then entered another long-term open-label study. One serious adverse event of mania was reported; all other treatment-emergent adverse events were mild or moderate in severity. Nausea, decreased appetite, somnolence, increased blood pressure, and upper respiratory tract infection were most frequently reported (three events each). No clinically relevant changes were noted in the laboratory parameters. ADHDRS-IV total score, inattention and hyperactivity/impulsivity subscores, and CGI-ADHD-S scores were statistically significantly improved at endpoint compared with baseline.
This study provides preliminary evidence to suggest that edivoxetine at doses ≤0.3 mg/kg/day is safe and may improve ADHD symptoms in pediatric patients. These results require confirmation in larger, double-blind, placebo-controlled trials.
本研究旨在评估选择性去甲肾上腺素再摄取抑制剂依地西汀治疗小儿注意力缺陷多动障碍(ADHD)开放标签研究的临床结果。
这是一项依地西汀的多队列开放标签研究,包括单剂量给药期(第1部分)和开放标签每日一次(QD)剂量长期给药期(第2部分)。12至17岁的青少年和6至11岁的儿童纳入第1部分,并继续进入第2部分,在那里他们接受0.05至0.3mg/kg依地西汀QD治疗≤12个月。通过不良事件、生命体征、体重、心电图和实验室检查评估安全性。在第2部分中,确定了注意力缺陷/多动障碍评定量表第四版-家长报告:研究者评分(ADHDRS-IV)和临床总体印象-ADHD-严重程度(CGI-ADHD-S)评分。
53例患者纳入第1部分,49例继续进入第2部分,平均暴露持续时间为22周。完成第2部分的31例患者随后进入另一项长期开放标签研究。报告了1例躁狂严重不良事件;所有其他治疗中出现的不良事件严重程度为轻度或中度。恶心、食欲减退、嗜睡、血压升高和上呼吸道感染报告最为频繁(各3例)。实验室参数未发现临床相关变化。与基线相比,终点时ADHDRS-IV总分、注意力不集中和多动/冲动子评分以及CGI-ADHD-S评分在统计学上有显著改善。
本研究提供了初步证据表明,≤0.3mg/kg/天剂量的依地西汀是安全的,可能改善小儿患者的ADHD症状。这些结果需要在更大规模的双盲、安慰剂对照试验中得到证实。