Yale Clinic for Attention and Related Disorders, Yale University School of Medicine, 1188 Whitney Ave., PO Box 6694, Hamden, New Haven, CT 06517, USA.
Postgrad Med. 2010 Sep;122(5):7-17. doi: 10.3810/pgm.2010.09.2196.
INTRODUCTION/OBJECTIVE: Executive function (EF) impairment in attention-deficit/hyperactivity disorder (ADHD) may account for behavioral symptoms such as poor concentration, impaired working memory, problems in shifting among tasks, and prioritizing and planning complex sets of tasks or completing long-term projects at work or school. Poor self-regulation and control of emotional behaviors frequently are seen in patients with ADHD. This study assessed EF behaviors in adults with ADHD at baseline and after 4 weeks of treatment with lisdexamfetamine dimesylate (LDX).
Executive function behavior was assessed using the Brown Attention-Deficit Disorder Scale (BADDS) during the 4-week open-label dose-optimization phase prior to a 2-period, randomized, double-blind, placebo-controlled crossover study of LDX (30-70 mg/day). The ADHD Rating Scale IV (ADHD-RS-IV) with adult prompts assessed ADHD symptoms. Change in EF behavioral symptoms was evaluated based on week 4 BADDS total and cluster scores; analyses of shifts from baseline among subjects with BADDS scores < 50, 50 to 59, 60 to 69, and ≥ 70; and scores less than or greater than baseline 90% confidence range (eg, reliably improved or worsened, respectively). Treatment-emergent adverse events (TEAEs) were described.
At week 4, BADDS total and cluster scores were reduced (ie, improved; all P < 0.0001 vs baseline [n = 127]). The ADHD-RS-IV with adult prompts scores also improved (all P < 0.0001 vs baseline). At week 4, 62.7% of subjects had a BADDS total score of < 50, and 78.9% were reliably improved; 1.4% were reliably worsened. Common TEAEs (≥ 5%) during the dose-optimization phase were decreased appetite (36.6%), dry mouth (30.3%), headache (19.7%), insomnia (18.3%), upper respiratory tract infection (9.9%), irritability (8.5%), nausea (7.7%), anxiety (5.6%), and feeling jittery (5.6%).
Clinically optimized doses of LDX (30-70 mg/day) significantly improved EF behaviors in adults with ADHD. Treatment-emergent adverse events with LDX were consistent with those observed with long-term stimulant use.
介绍/目的：注意力缺陷多动障碍（ADHD）患者的执行功能（EF）受损可能导致行为症状，例如注意力不集中、工作记忆受损、任务转换困难、优先安排和规划复杂任务或完成工作或学校的长期项目。ADHD 患者经常出现自我调节和情绪行为控制能力差的情况。本研究评估了基线时接受赖氨酸右旋苯丙胺二甲硫酸盐（LDX）治疗 4 周后的 ADHD 成人的 EF 行为。
在为期 4 周的开放标签剂量优化阶段，使用布朗注意缺陷障碍量表（BADDS）评估执行功能行为，随后进行为期 2 期、随机、双盲、安慰剂对照的 LDX（30-70mg/天）交叉研究。ADHD 评定量表第四版（ADHD-RS-IV）结合成人提示评估 ADHD 症状。根据第 4 周 BADDS 总分和聚类评分评估 EF 行为症状的变化；分析 BADDS 评分<50、50-59、60-69 和≥70 的受试者从基线的变化；以及评分低于或高于基线 90%置信区间（例如，分别可靠改善或恶化）。描述治疗中出现的不良事件（TEAEs）。
第 4 周时，BADDS 总分和聚类评分降低（即改善；均 P<0.0001 与基线[n=127]）。ADHD-RS-IV 成人提示评分也有所改善（均 P<0.0001 与基线）。第 4 周时，62.7%的受试者 BADDS 总分<50，78.9%的受试者改善可靠；1.4%的受试者可靠恶化。剂量优化阶段常见的不良事件（≥5%）包括食欲减退（36.6%）、口干（30.3%）、头痛（19.7%）、失眠（18.3%）、上呼吸道感染（9.9%）、易怒（8.5%）、恶心（7.7%）、焦虑（5.6%）和感觉紧张（5.6%）。
优化剂量的 LDX（30-70mg/天）可显著改善 ADHD 成人的 EF 行为。LDX 治疗中出现的不良事件与长期使用兴奋剂一致。
