University of Dundee, UK.
Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
J Am Acad Child Adolesc Psychiatry. 2014 Jun;53(6):647-657.e1. doi: 10.1016/j.jaac.2014.01.017. Epub 2014 Mar 4.
In this phase 3 extension study, the long-term maintenance of efficacy of lisdexamfetamine dimesylate (LDX) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) was evaluated using a randomized-withdrawal study design.
European and US patients (6-17 years; N = 276) with ADHD were entered into a 26-week open-label trial of LDX treatment. Those who completed the open-label period (n = 157) were randomized 1:1 to their optimized dose of LDX (30, 50, or 70 mg per day) or placebo for a 6-week randomized-withdrawal period (RWP). The primary efficacy measure was the proportion of patients meeting treatment failure criteria (≥50% increase in ADHD Rating Scale IV total score and ≥2-point increase in Clinical Global Impressions-Severity of Illness [CGI-S] score, compared with RWP start point). Safety and tolerability were also evaluated.
During the RWP (LDX, n = 78; placebo, n = 79), significantly fewer patients receiving LDX met treatment failure criteria (15.8%) compared with those receiving placebo (67.5%; difference = -51.7%; 95% confidence interval = -65.0, -38.5; p < .001 ). Most treatment failures occurred at or before the week 2 visit after randomization. Treatment-emergent adverse events were reported in 39.7% and 25.3% of patients receiving LDX and placebo, respectively, during the RWP.
These data demonstrate the maintenance of efficacy of LDX during long-term treatment in children and adolescents with ADHD. The rapid return of symptoms on LDX withdrawal demonstrates the need for continuing treatment. The safety profile of LDX was consistent with that of other stimulants. Clinical trial registration information-Double-Blind, Placebo-Controlled, Randomized Withdrawal, Extension, Safety and Efficacy Study of LDX in Children and Adolescents Aged 6-17; http://clinicaltrials.gov; NCT00784654.
在这项 3 期扩展研究中，采用随机撤药研究设计，评估 lisdexamfetamine dimesylate（LDX）在患有注意缺陷多动障碍（ADHD）的儿童和青少年中的长期疗效维持情况。
欧洲和美国的 276 名 ADHD 患者入组了为期 26 周的 LDX 治疗开放性标签试验。完成开放性标签期的患者（n=157）按 1:1 随机分为优化剂量 LDX（每天 30、50 或 70mg）或安慰剂治疗 6 周的随机撤药期（RWP）。主要疗效指标为符合治疗失败标准的患者比例（与 RWP 起始点相比，ADHD 评定量表 IV 总分增加≥50%，临床总体印象-严重程度量表[CGI-S]评分增加≥2 分）。同时评估安全性和耐受性。
在 RWP 期间（LDX，n=78；安慰剂，n=79），接受 LDX 治疗的患者符合治疗失败标准的比例明显低于接受安慰剂治疗的患者（15.8% vs. 67.5%；差异=-51.7%；95%置信区间=-65.0，-38.5；p<0.001）。大多数治疗失败发生在随机分组后第 2 周访视时或之前。在 RWP 期间，分别有 39.7%和 25.3%的接受 LDX 和安慰剂治疗的患者报告出现治疗中出现的不良事件。
这些数据表明，在 ADHD 儿童和青少年的长期治疗中，LDX 的疗效得以维持。LDX 撤药后症状迅速复发，表明需要继续治疗。LDX 的安全性与其他兴奋剂一致。
临床试验注册信息-双盲、安慰剂对照、随机撤药、扩展、LDX 治疗 6-17 岁儿童和青少年的安全性和疗效研究；http://clinicaltrials.gov；NCT00784654。
