Efficacy of lisdexamfetamine dimesylate in children with attention-deficit/hyperactivity disorder previously treated with methylphenidate: a post hoc analysis.
Efficacy of lisdexamfetamine dimesylate in children with attention-deficit/hyperactivity disorder previously treated with methylphenidate: a post hoc analysis.
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DOI：
10.1186/1753-2000-5-35
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发表时间：
2011-11-04
影响因子：
5.6
通讯作者：
Lasser R
中科院分区：
文献类型：
--
作者：
Jain R;Babcock T;Burtea T;Dirks B;Adeyi B;Scheckner B;Lasser R
注意力缺陷多动障碍（ADHD）是一种常见的神经行为精神障碍，困扰儿童，据报道，全球患病率为2.4%至19.8%。兴奋剂（哌甲酯[MPH]和安非他明）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，而安非他明具有额外的突触前活性。虽然MPH和安非他明可以有效地控制大多数儿科患者的ADHD症状，但许多人仍然无法对任何一种做出最佳反应。给药后，前药兴奋剂二甲磺酸利右苯丙胺（LDX）在血液中转化为l-赖氨酸和治疗活性的d-苯丙胺。本研究的目的是评价LDX在入组4周安慰剂对照LDX试验前接受MPH治疗仍有症状（即，非缓解者; ADHD评定量表IV [ADHD-RS-IV]总分> 18）的ADHD儿童中的临床疗效，并与总体人群进行比较。在对来自多中心、随机、双盲、强制剂量滴定研究的数据进行的事后分析中，我们评估了LDX在筛选时既往接受和未接受MPH治疗的6-12岁儿童中的临床疗效。在筛选、基线和终点时，使用ADHD-RS-IV量表、Conners父母评定量表修订版简表（CPRS-R）和临床总体印象改善量表评估ADHD症状。将ADHD-RS-IV总分和CPRS-R ADHD指数评分总结为平均值（SD）。亚组分析的临床应答定义为ADHD-RS-IV评分较基线降低≥ 30%且CGI-I评分为1或2。使用Dunnett检验比较所有组中较基线的变化。达到1例临床应答者或1例症状缓解者所需治疗的数量计算为终点时活性治疗组和安慰剂组比例差异的倒数。在290名随机参与者中，28名在筛选时接受MPH治疗，其中26名仍有症状（ADHD-RS-IV > 18）。该亚组的ADHD-RS-IV总分、较基线的变化、临床反应性和症状缓解率与总体人群相当。LDX的安全性和耐受性与目前可用的其他兴奋剂相当。在这项分析中，尽管MPH治疗，但具有显著临床ADHD症状的儿童在LDX治疗期间得到改善，并且其症状的改善与总体研究人群相似。ClinicalTrials.gov：NCT00556296
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. 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. 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. 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. ClinicalTrials.gov: NCT00556296