Findling Robert L, Cutler Andrew J, Saylor Keith, Gasior Maria, Hamdani Mohamed, Ferreira-Cornwell M Celeste, Childress Ann C
Johns Hopkins Medicine and the Kennedy Krieger Institute, Johns Hopkins University, Baltimore, MD 21287, USA.
J Child Adolesc Psychopharmacol. 2013 Feb;23(1):11-21. doi: 10.1089/cap.2011.0088.
Information on psychostimulant treatment in long-term studies for attention-deficit/hyperactivity disorder (ADHD) in adolescents is limited. This study aimed to assess the safety and effectiveness of lisdexamfetamine dimesylate (LDX) over 52 weeks in adolescents with ADHD.
This open-label multicenter study enrolled eligible participants after their participation in a randomized, double-blind, placebo-controlled 4 week trial in adolescents with ADHD. Following a 4 week dose-optimization phase, participants were maintained on treatment for up to ∼48 weeks on an optimal dose. Safety assessments included treatment-emergent adverse events (TEAEs), vital signs, laboratory findings, and electrocardiograms. Effectiveness measures included the ADHD Rating Scale IV (ADHD-RS-IV; primary) and Clinical Global Impressions-Improvement (CGI-I). The Youth Quality of Life-Research Version (YQOL-R) was also included in this study; raw scores are transformed to a 0-100 point scale.
Of 269 enrolled (from the antecedent study), 265 (98.5%) were in the safety population and effectiveness population. Common TEAEs (≥5%) with LDX included upper respiratory tract infection (21.9%), decreased appetite (21.1%), headache (20.8%), decreased weight (16.2%), irritability (12.5%), insomnia (12.1%), nasopharyngitis (7.2%), influenza (6.8%), dizziness (5.3%), and dry mouth (5.3%). At end point, for all LDX doses in the overall safety population, mean (SD) increase from baseline in systolic blood pressure was 2.3 (10.53) mm Hg, diastolic blood pressure was 2.5 (8.37) mm Hg, and pulse rate was 6.3 (12.74) bpm. No clinically meaningful electrocardiogram or vital sign changes were observed. At end point with LDX treatment, the ADHD-RS-IV mean (SD) total score change from antecedent study baseline was -26.2 (9.75) (p<0.001); 87.2% of participants were improved (CGI-I=1 or 2). Baseline (antecedent study) mean (SD) YQOL-R perceptual total score was 79.8 (11.28) and increased by 3.9 (9.73) at end point (p<0.001).
LDX demonstrated a long-term safety profile similar to that of other long-acting psychostimulants and was effective, as indicated by improvements in ADHD symptoms and participant-perceived YQOL, in adolescents with ADHD.
NCT00764868, http://www.clinicaltrials.gov/ct2/show/NCT00764868?term=SPD489-306&rank=1.
关于青少年注意力缺陷多动障碍（ADHD）长期研究中精神兴奋剂治疗的信息有限。本研究旨在评估52周内二甲磺酸赖右苯丙胺（LDX）治疗青少年ADHD的安全性和有效性。
这项开放标签的多中心研究在符合条件的参与者完成一项针对青少年ADHD的随机、双盲、安慰剂对照4周试验后招募他们。经过4周的剂量优化阶段后，参与者以最佳剂量维持治疗长达约48周。安全性评估包括治疗中出现的不良事件（TEAE）、生命体征、实验室检查结果和心电图。有效性指标包括ADHD评定量表第四版（ADHD-RS-IV；主要指标）和临床总体印象改善量表（CGI-I）。本研究还纳入了青少年生活质量研究版（YQOL-R）；原始分数转换为0至100分制。
在269名入组者（来自前期研究）中，265名（98.5%）纳入安全性人群和有效性人群。LDX常见的TEAE（≥5%）包括上呼吸道感染（21.9%）、食欲减退（～21.1%）、头痛（20.8%）、体重减轻（16.2%）、易激惹（12.5%）、失眠（12.1%）、鼻咽炎（7.2%）、流感（6.8%）、头晕（5.3%）和口干（5.3%）。在终点时，在总体安全性人群中所有LDX剂量组，收缩压较基线的平均（标准差）升高为2.3（10.53）mmHg，舒张压为2.5（8.37）mmHg，脉搏率为6.3（12.74）次/分钟。未观察到具有临床意义的心电图或生命体征变化。在LDX治疗终点时，ADHD-RS-IV较前期研究基线的平均（标准差）总分变化为-26.2（9.75）（p<0.001）；87.2%的参与者病情改善（CGI-I=1或2）。基线（前期研究）YQOL-R感知总分的平均（标准差）为79.8（11.28），终点时升高了3.9（9.73）（p<0.001）。
LDX显示出与其他长效精神兴奋剂相似的长期安全性，并且对青少年ADHD有效，表现为ADHD症状改善以及参与者感知的生活质量提高。
NCT00764868，http://www.clinicaltrials.gov/ct2/show/NCT00764868?term=SPD489-306&rank=1 。
