A Randomized, Placebo-Controlled Trial of Guanfacine Extended Release in Adolescents With Attention-Deficit/Hyperactivity Disorder
A Randomized, Placebo-Controlled Trial of Guanfacine Extended Release in Adolescents With Attention-Deficit/Hyperactivity Disorder
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DOI：
10.1016/j.jaac.2015.08.016
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发表时间：
2015-11-01
影响因子：
13.3
通讯作者：
Cutler, Andrew J.
中科院分区：
文献类型：
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作者：
Wilens, Timothy E.;Robertson, Brigitte;Cutler, Andrew J.
目的：尽管注意力缺陷/多动障碍(ADHD)一直持续到青春期，但对于使用非兴奋剂治疗青少年ADHD的情况知之甚少。这项为期13周的多中心、随机、双盲、安慰剂对照试验，对13岁至17岁的青少年ADHD患者每日服用1-7 mg，进行为期13周的安全性和有效性评估。主要终点是ADHD评定量表-IV总分与基线的变化；关键次要终点包括临床总体印象-疾病严重程度评分(CGI-S)和13周时Weiss功能障碍评定量表-父母报告(WFIRS-P)的学习、学校领域和家庭领域得分。大多数参与者接受了3、4、5或6毫克的最佳剂量(分别为30[22.9%]、26[19.8%]、27[20.6%]或24[18.3%])，其中46.5%的参与者接受了高于当前批准的最大剂量限制4毫克的最佳剂量。与安慰剂相比，服用GXR的参与者在ADHD-RS-IV总分方面表现出改善(平均得分变化最小二乘法，-24.55[GXR]对-18.53[安慰剂]；效应大小，0.52；p<；.001)。与安慰剂组相比，服用GXR的更多参与者的CGI-S得分也有显著改善(50.6%比36.1%；p=.010)。在第13周，两个WFIRS-P领域的治疗之间没有统计学上的显著差异。大多数治疗出现的不良事件都是轻微到中度的，其中与镇静相关的事件最常见。结论：GXR与青少年ADHD症状的显著改善有关。GXR耐受性良好，没有新的安全信号报道。13-17岁青少年使用盐酸胍缓释剂诊断为注意力缺陷/多动障碍的临床试验注册信息剂量优化；http://ClinicalTrials.gov/；NCT01081132.
Objective: Despite the continuity of attention-deficit/hyperactivity disorder (ADHD) into adolescence, little is known regarding use of nonstimulants to treat ADHD in adolescents. This phase 3 trial evaluated the safety and efficacy of guanfacine extended release (GXR) in adolescents with ADHD.Method: This 13-week, multicenter, randomized, double-blind, placebo-controlled trial evaluated once-daily GXR (1-7 mg per day) in adolescents with ADHD aged 13 to 17 years. The primary endpoint was the change from baseline in the ADHD Rating Scale-IV (ADHD-RS-IV) total score; key secondary endpoints included scores from the Clinical Global Impressions-Severity of Illness (CGI-S), and Learning and School domain and Family domain scores from the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) at week 13.Results: A total of 314 participants were randomized (GXR, n = 157; placebo, n = 157). The majority of participants received optimal doses of 3, 4, 5, or 6 mg (30 [22.9%], 26 [19.8%], 27 [20.6%], or 24 [18.3%] participants, respectively), with 46.5% of participants receiving an optimal dose above the currently approved maximum dose limit of 4 mg. Participants receiving GXR showed improvement in ADHD-RS-IV total score compared with placebo (least-squares mean score change, -24.55 [GXR] versus -18.53 [placebo]; effect size, 0.52; p < .001). More participants on GXR also showed significant improvement in CGI-S scores compared with placebo (50.6% versus 36.1%; p = .010). There was no statistically significant difference between treatments at week 13 in the 2 WFIRS-P domains. Most treatment-emergent adverse events were mild to moderate, with sedation-related events reported most commonly.Conclusion: GXR was associated with statistically significant improvements in ADHD symptoms in adolescents. GXR was well tolerated, with no new safety signals reported.Clinical Trial Registration Information Dose-Optimization in Adolescents Aged 13-17 Diagnosed With Attention-Deficit/Hyperactivity Disorder (ADHD) Using Extended-Release Guanfacine HCl; http://ClinicalTrials.gov/;NCT01081132.