A double-blind, placebo-controlled withdrawal trial of dexmethylphenidate hydrochloride in children with attention deficit hyperactivity disorder
A double-blind, placebo-controlled withdrawal trial of dexmethylphenidate hydrochloride in children with attention deficit hyperactivity disorder
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DOI：
10.1089/cap.2004.14.542
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发表时间：
2004-12-01
影响因子：
1.9
通讯作者：
Zeldis, JB
中科院分区：
文献类型：
--
作者：
Arnold, LE;Lindsay, RL;Zeldis, JB
目的：d,l-苏型苯甲酸甲酯盐酸盐 (d,l-MPH) 是注意力缺陷多动障碍 (ADHD) 最常见的治疗方法。先前的报告显示，纯化的d-异构体(盐酸哌醋甲酯，d-MPH，Focalin TM )具有安慰剂对照功效，与dl相比效力为2:1，并建议作用持续时间为6小时。本研究通过研究安慰剂对照的停药效果和重新测试作用持续时间来补充该报告。方法：对 d-MPH（2.5-10 mg，每天两次）进行为期 6 周的开放标签滴定，随后对有反应者进行双盲、安慰剂对照、为期 2 周的停药研究。结果：在开放滴定中，89 名入组患者中有 82% 实现了临床总体印象改善(CGI-I) 评级大大提高。只有 5 名患者因不良事件而停药。 75 名患者继续接受安慰剂对照停药。对于随机分配的 d-MPH (n = 35) 组和安慰剂组 (n = 40)，平均年龄分别为 10.1 +/- 2.9 和 9.9 +/- 2.7 岁，86% 和 78% 为男性，70.6% 和 80.0% 分别服用每日两次 10 mg 的最高剂量。每组中80%为合并型ADHD，20%为注意力不集中型。到 2 周安慰剂屏蔽戒断结束时，安慰剂患者（39 名中的 24 名）比 d-MPH 继续治疗者（35 名中的 6 名）复发的人数明显更多（61.5% 对比 17.1%，p = 0.001）。与 d-MPH 继续治疗者相比，安慰剂患者在两周内对 18 种 ADHD 症状的老师评分为 0-3 级（P = 0.028）、下午 3 点和下午 3 点的病情恶化程度明显更大。下午 6 点家长 ADHD 症状评分（分别为 p = 0.0026 和 p = 0.0381），以及诊所（下午 2-3 点）和家庭（下午 6 点）数学测试（分别为 p = 0.024 和 p < 0.0001）。下午 6 点评分重复了先前研究中报告的 6 小时时的显着效果。结论：d-MPH 是安全、可耐受且有效的，双盲停药 6 小时时与安慰剂的显着差异表明 d-MPH 的效果持续时间为 6 小时。
Objectives: d,l-threo-methylpheni date HCl (d,l-MPH) is the most common treatment of attention deficit hyperactivity disorder (ADHD). A previous report showed placebo-controlled efficacy for the purified d-isomer (dexmethylphenidate hydrochloride, d-MPH, Focalin(TM)) with a 2 :1 potency compared to dl, and suggested a 6-hour duration of action. This study complements that report by studying the effect of placebo-controlled discontinuation and retesting the duration of action.Methods: A 6-week, open-label titration of d-MPH (2.5-10 mg twice-a-day) was followed by a double-blind, placebo-controlled, 2-week withdrawal study of responders.Results: In the open titration, 82% of the 89 enrolled patients achieved a Clinical Global Impression-Improvement (CGI-I) rating of much or very much improved. Only 5 patients discontinued for adverse events. Seventy-five patients continued into the placebo-controlled discontinuation. For the randomly assigned d-MPH (n = 35) and placebo (n = 40) groups, mean ages, respectively, were 10.1 +/- 2.9 and 9.9 +/- 2.7 years, 86% and 78% were male, and 70.6% and 80.0% took the ceiling dose of 10 mg twice-daily, respectively. Each group had 80% combined-type ADHD and 20% inattentive type. By the end of the 2-week, placebo-masked withdrawal, significantly more placebo patients (24 of 39) than d-MPH continuers (6 of 35) relapsed (61.5% versus 17.1%, p = 0.001). Compared to d-MPH continuers, placebo patients deteriorated significantly more in the 2-week period on teacher ratings of the 18 ADHD symptoms rated 0-3 (P = 0.028), the 3 p.m. and 6 p.m. parent ADHD symptom ratings (p = 0.0026 and p = 0.0381, respectively), and clinic (2-3 p.m.) and home (6 p.m.) Math Tests (p = 0.024 and p < 0.0001, respectively). The 6 p.m. scores replicated the significant effect at 6 hours reported in the previous study.Conclusions: d-MPH is safe, tolerable, and effective, with a 6-hour duration of effect suggested by the significant difference from placebo at 6 hours on a double-blind discontinuation.