Lisdexamfetamine dimesylate in the treatment of attention-deficit/hyperactivity disorder: pharmacokinetics, efficacy and safety in children and adolescents

Background Psychostimulants (methylphenidate and amphetamines) are considered first-line therapy for attention-deficit/hyperactivity disorder (ADHD). Lisdexamfetamine dimesylate (LDX) is a new psychostimulant approved for the treatment of ADHD in Brazil. The pharmacologically active fraction, d-amphetamine, is gradually released by hydrolysis of the LDX prodrug. Objectives To perform a systematic review of the literature of the efficacy and safety of LDX in the treatment of ADHD in children and adolescents. Methods Medline/PubMed searches for “d-amfetamine”, “lisdexamfetamine” and “lisdexamfetamine dimesylate” were conducted including articles available from January 2000 to November 2013. Additional references were identified using references listed in those articles. Further data on LDX were requested from its manufacturer. Results Thirty-one papers were found related to ADHD treatment in children and adolescents. Discussion The therapeutic benefits of LDX in children with ADHD are achieved as early as 1.5 hours after its administration and last for up to 13 hours, with efficacy comparable or superior to that of other available psychostimulants. The literature also reports efficacy in long-term treatment, with safety and tolerability profiles comparable to those of other stimulants used for the treatment of ADHD. Most of the adverse events associated with LDX are considered to be mild or moderate in severity, with the most common being loss of appetite and insomnia.

研究背景：精神兴奋剂（哌甲酯（methylphenidate）与苯丙胺类药物）被视为注意缺陷多动障碍（attention-deficit/hyperactivity disorder，ADHD）的一线治疗方案。二甲磺酸赖右苯丙胺（Lisdexamfetamine Dimesylate，LDX）是一款在巴西获批用于ADHD治疗的新型精神兴奋剂，其药理活性成分为d-苯丙胺，可通过LDX前体药物的水解反应逐步释放。
研究目的：系统回顾现有文献，评估LDX用于儿童及青少年ADHD治疗的疗效与安全性。
研究方法：检索Medline/PubMed数据库，检索词为"d-amfetamine"、"lisdexamfetamine"及"lisdexamfetamine dimesylate"，检索时限为2000年1月至2013年11月；同时通过纳入文献的参考文献列表补充获取相关资料，并向LDX的生产商索要额外研究数据。
研究结果：共检索到31篇与儿童及青少年ADHD治疗相关的文献。
研究讨论：儿童ADHD患者服用LDX后，治疗获益可在给药后1.5小时内显现，药效持续时长可达13小时，其疗效与现有其他精神兴奋剂相当甚至更优；现有文献同时证实了LDX用于长期治疗的有效性，其安全性与耐受性与其他用于ADHD治疗的兴奋剂类药物相仿。LDX相关的大多数不良事件均为轻中度，最常见的不良反应为食欲减退与失眠。