BACKGROUND Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral psychiatric disorder that afflicts children, with a reported prevalence of 2.4% to 19.8% worldwide. Stimulants (methylphenidate [MPH] and amphetamine) are considered first-line ADHD pharmacotherapy. MPH is a catecholamine reuptake inhibitor, whereas amphetamines have additional presynaptic activity. Although MPH and amphetamine can effectively manage ADHD symptoms in most pediatric patients, many still fail to respond optimally to either. After administration, the prodrug stimulant lisdexamfetamine dimesylate (LDX) is converted to l-lysine and therapeutically active d-amphetamine in the blood. The objective of this study was to evaluate the clinical efficacy of LDX in children with ADHD who remained symptomatic (ie, nonremitters; ADHD Rating Scale IV [ADHD-RS-IV] total score > 18) on MPH therapy prior to enrollment in a 4-week placebo-controlled LDX trial, compared with the overall population. METHODS In this post hoc analysis of data from a multicenter, randomized, double-blind, forced-dose titration study, we evaluated the clinical efficacy of LDX in children aged 6-12 years with and without prior MPH treatment at screening. ADHD symptoms were assessed using the ADHD-RS-IV scale, Conners' Parent Rating Scale-Revised short form (CPRS-R), and Clinical Global Impressions-Improvement scale, at screening, baseline, and endpoint. ADHD-RS-IV total and CPRS-R ADHD Index scores were summarized as mean (SD). Clinical response for the subgroup analysis was defined as a ≥ 30% reduction from baseline in ADHD-RS-IV score and a CGI-I score of 1 or 2. Dunnett test was used to compare change from baseline in all groups. Number needed to treat to achieve one clinical responder or one symptomatic remitter was calculated as the reciprocal of the difference in their proportions on active treatment and placebo at endpoint. RESULTS Of 290 randomized participants enrolled, 28 received MPH therapy at screening, of which 26 remained symptomatic (ADHD-RS-IV > 18). ADHD-RS-IV total scores, changes from baseline, clinical responsiveness, and rates of symptomatic remission in this subgroup were comparable to the overall population. The safety and tolerability profiles for LDX were comparable to other stimulants currently available. CONCLUSION In this analysis, children with significant clinical ADHD symptoms despite MPH treatment improved during treatment with LDX and experienced similar improvements in their symptoms as the overall study population. TRIAL REGISTRATION ClinicalTrials.gov: NCT00556296.

中文翻译：

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lisdexamfetamine 二甲磺酸盐对先前用哌甲酯治疗的注意力缺陷/多动障碍儿童的疗效：事后分析。

背景注意力缺陷/多动障碍 (ADHD) 是一种常见的神经行为精神障碍，它困扰着儿童，据报道，全世界的患病率为 2.4% 至 19.8%。兴奋剂（哌甲酯 [MPH] 和苯丙胺）被认为是 ADHD 的一线药物治疗。MPH 是一种儿茶酚胺再摄取抑制剂，而苯丙胺则具有额外的突触前活性。尽管 MPH 和安非他明可以有效控制大多数儿科患者的 ADHD 症状，但许多人仍然无法对其中任何一种做出最佳反应。给药后，前药兴奋剂赖地苯丙胺二甲磺酸盐 (LDX) 在血液中转化为 l-赖氨酸和具有治疗活性的 d-苯丙胺。本研究的目的是评估 LDX 对仍有症状的 ADHD 儿童（即不缓解；ADHD 评定量表 IV [ADHD-RS-IV] 总分 > 18) 在参加 4 周安慰剂对照 LDX 试验前 MPH 治疗，与总体人群相比。方法 在这项多中心、随机、双盲、强制剂量滴定研究数据的事后分析中，我们评估了 LDX 在 6-12 岁儿童中的临床疗效，在筛选时既往接受过 MPH 治疗，也未接受过 MPH 治疗。在筛选、基线和终点时，使用 ADHD-RS-IV 量表、Conners' Parent Rating Scale-Revised Short Form (CPRS-R) 和临床总体印象改善量表评估 ADHD 症状。ADHD-RS-IV 总分和 CPRS-R ADHD 指数得分总结为平均值 (SD)。亚组分析的临床反应定义为 ADHD-RS-IV 评分比基线降低 30% 以上，CGI-I 评分为 1 或 2。Dunnett 检验用于比较所有组从基线的变化。达到一名临床反应者或一名症状缓解者所需治疗的人数计算为终点时积极治疗和安慰剂的比例差异的倒数。结果 在纳入的 290 名随机参与者中，28 人在筛选时接受了 MPH 治疗，其中 26 人仍有症状（ADHD-RS-IV > 18）。该亚组的 ADHD-RS-IV 总分、相对于基线的变化、临床反应性和症状缓解率与总体人群相当。LDX 的安全性和耐受性特征与目前可用的其他兴奋剂相当。结论 在这个分析中，尽管 MPH 治疗，但仍有显着临床 ADHD 症状的儿童在 LDX 治疗期间有所改善，并且其症状的改善与整个研究人群相似。试验注册 ClinicalTrials.gov：NCT00556296。