Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, P.O. Box: 12 21 20, D-68072, Mannheim, Germany,
CNS Drugs. 2013 Oct;27(10):829-40. doi: 10.1007/s40263-013-0095-5.
Optimal management of attention deficit hyperactivity disorder (ADHD) aims not only to ameliorate patients' symptoms, but also to improve health-related quality of life (HRQL) and functioning. A pivotal, 7-week, randomized, double-blind, placebo-controlled, phase III study in children and adolescents in ten European countries demonstrated that the stimulant prodrug lisdexamfetamine dimesylate (LDX) is an effective and generally well-tolerated treatment for symptoms of ADHD.
The aim of this study was to assess HRQL and functional impairment outcomes in this clinical trial, using the Child Health and Illness Profile-Child Edition: Parent Report Form (CHIP-CE:PRF) and the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P), respectively.
Patients (aged 6-17 years) with diagnosed ADHD and a baseline ADHD Rating Scale IV total score ≥28 were randomized (1:1:1) to 7 weeks of double-blind treatment with once-daily LDX, placebo or the reference treatment, osmotic-release oral system methylphenidate (OROS-MPH). Participants' parents (or legally authorized representatives) completed the CHIP-CE:PRF and WFIRS-P questionnaires at baseline, at weeks 4 and 7, and/or at early termination. Endpoint was defined as the last on-treatment visit with valid data (≤30 % missing items). The CHIP-CE:PRF Achievement domain was pre-specified as the primary HRQL outcome.
The full analysis set comprised 317 patients (LDX, n = 104; placebo, n = 106; OROS-MPH, n = 107), the majority of whom completed the study (LDX, n = 77; placebo, n = 42; OROS-MPH, n = 72). Baseline CHIP-CE:PRF T-scores in four of the five domains were ≥1 standard deviation below norms (US community samples). Compared with placebo, LDX was associated with statistically significantly improved T-scores from baseline to endpoint in these four domains, with effect sizes of 1.280 (p < 0.001) in Achievement, 1.079 (p < 0.001) in Risk Avoidance, 0.421 (p < 0.01) in Resilience and 0.365 (p < 0.05) in Satisfaction. In LDX-treated patients, placebo-adjusted improvements from baseline to endpoint in WFIRS-P scores were statistically significant (p < 0.001) for total score and four of the six domains, with effect sizes of 0.924 (total score), 1.249 (Learning and School), 0.730 (Family), 0.643 (Social Activities) and 0.640 (Risky Activities). OROS-MPH treatment showed similar patterns of improvement from baseline to endpoint in both CHIP-CE:PRF and WFIRS-P scores.
Baseline HRQL and functional impairment scores reflect the burden of untreated ADHD. The benefits of short-term stimulant treatment in children and adolescents with ADHD extend beyond symptomatic relief and impact positively on HRQL and daily functioning.
注意力缺陷多动障碍（ADHD）的最佳治疗方案不仅要改善患者的症状，还要改善与健康相关的生活质量（HRQL）和功能。一项为期 7 周、在 10 个欧洲国家的儿童和青少年中进行的、关键性、随机、双盲、安慰剂对照、III 期研究表明，兴奋剂前体药物赖氨酸右旋苯丙胺二甲硫酸盐（LDX）是一种有效且通常耐受性良好的 ADHD 症状治疗药物。
本研究旨在使用儿童健康和疾病概况-儿童版：家长报告表（CHIP-CE：PRF）和 Weiss 功能障碍评定量表-家长报告（WFIRS-P）分别评估该临床试验中的 HRQL 和功能障碍结局。
诊断为 ADHD 且基线 ADHD 评定量表 IV 总分≥28 的患者（6-17 岁）按 1:1:1 的比例随机分为 7 周的双盲治疗，分别接受每日一次 LDX、安慰剂或参考药物——奥昔布宁控释口服混悬液（OROS-MPH）治疗。参与者的父母（或法定授权代表）在基线、第 4 周和第 7 周以及/或提前终止时填写 CHIP-CE：PRF 和 WFIRS-P 问卷。终点定义为最后一次有治疗数据的就诊（≤30%缺失项目）。CHIP-CE：PRF 成就领域被预先指定为主要 HRQL 结局。
共有 317 名患者（LDX，n=104；安慰剂，n=106；OROS-MPH，n=107）纳入全分析集，其中大多数患者完成了研究（LDX，n=77；安慰剂，n=42；OROS-MPH，n=72）。五个领域中的四个领域的基线 CHIP-CE：PRF T 评分均低于正常值（美国社区样本）1 个标准差。与安慰剂相比，LDX 与这些四个领域从基线到终点的 T 评分显著改善相关，效应大小分别为 1.280（p<0.001）在成就方面，1.079（p<0.001）在风险回避方面，0.421（p<0.01）在恢复力方面，0.365（p<0.05）在满意度方面。在 LDX 治疗的患者中，从基线到终点，WFIRS-P 评分的安慰剂调整后改善在总分和六个领域中的四个领域均具有统计学意义（p<0.001），效应大小分别为 0.924（总分）、1.249（学习和学校）、0.730（家庭）、0.643（社会活动）和 0.640（冒险活动）。OROS-MPH 治疗在 CHIP-CE：PRF 和 WFIRS-P 评分方面也显示出从基线到终点相似的改善模式。
基线 HRQL 和功能障碍评分反映了未经治疗的 ADHD 的负担。短期兴奋剂治疗对儿童和青少年 ADHD 的益处不仅限于症状缓解，还对 HRQL 和日常功能产生积极影响。
