研究背景——托莫西汀概述
托莫西汀是全球第一个批准治疗注意缺陷多动障碍（ADHD）的非兴奋性药物。
2002 年在美国上市至今，已有 68 个国家，超过 600 万患者使用托莫西汀 ，证明了其良好的耐受性和有效性。
2007 年托莫西汀在中国获准治疗儿童/青少年 ADHD。
近年来，对托莫西汀的研究呈逐年上升趋势。
托莫西汀的作用机制
托莫西汀是选择性去甲肾上腺素再摄取抑制剂，通过增加前额叶皮层突触间隙去甲肾上腺素（NE）和多巴胺（DA）的浓度发挥治疗 ADHD 的作用，如下图所示：[2]
托莫西汀无滥用风险：
托莫西汀增加前额叶皮质 DA 浓度，但不增加伏隔核和纹状体 DA 水平，不作用于中脑边缘系统，因此无诱发抽动和滥用风险 [3]。
托莫西汀的起效特点
托莫西汀平稳起效：
多项研究显示，托莫西汀通常在 4 周内起效，部分研究提示第 1 周即起效。[4-8]
托莫西汀的疗效随治疗时间延长而增加：
研究显示，托莫西汀治疗儿童 ADHD 第 4 周时，明显改善（ADHD-RS 减分值 ≥ 40%）的患者比例达 47% 左右，该比例随治疗时间上升，在 52 周时达 96%。[9] 最初几周的疗效可预测最终的治疗效果。[4] 对于治疗初期「无反应」者，继续治疗仍有可能获得改善。[10]
托莫西汀的推荐剂量 [11，12]：
体重不足 70 公斤的儿童和青少年用量
起始剂量：0.5 mg/kg/天，并且在 3 天的最低用量之后增加给药量，至每日总目标剂量 1.2 mg/kg/天。
最大剂量：对儿童和青少年，每日最大剂量不应超过 1.4 mg/kg 或 100 mg，选其中较小的一个剂量。
体重超过 70 公斤的儿童、青少年
起始剂量：40 mg 天，并且在 3 天的最低用量之后增加给药量，至每日总目标剂量 80 mg/天，每日早晨单次服药或早晨和傍晚平均分为两次服用。
最大剂量：100 mg/天。
增加给药次数可改善疗效：
147 例托莫西汀一天一次治疗无反应的儿童患者，改为一天两次给药后，75% 的患者获得了治疗反应。[13]
一项纳入 288 人的安慰剂对照研究表明：早晨给药：ADHD-RS 总分和过度活跃/冲动亚评分下降更多，而夜间给药耐受性更好。[14]
托莫西汀的短期疗效评价
至少 9 项研究报道，对于未经治疗的患者，托莫西汀可有效改善 ADHD 核心症状、功能结局和生活质量。[8, 15, 16]
两项荟萃分析显示，托莫西汀的短期疗效不劣于兴奋剂。[17]
部分经其他治疗不佳的患者换用托莫西汀后短期内症状得到改善。[18, 19]
托莫西汀的长期疗效评价
5 项上市后研究 [20-24] 报告了托莫西汀长期疗效，观察时间范围：9 个月-2 年。结果提示托莫西汀治疗 ADHD 的疗效可持续至少 2 年；且治疗 ADHD 的长期疗效与兴奋剂相当。
托莫西汀对 ADHD 共病的疗效
大量对于 ADHD 共病的研究显示，托莫西汀可用于治疗共病 ODD、抽动、焦虑、广泛性发育障碍等疾病的 ADHD 患者，且托莫西汀在改善 ADHD 症状的同时，并不加重共病的症状，有的甚至可以改善某些共病症状。 [25-32]
托莫西汀对生长发育无显著影响
一项荟萃分析显示，托莫西汀长期治疗对 ADHD 青少年患者体重及身高无显著影响。[20]
另一项数据综合分析探讨了托莫西汀治疗 ADHD 患儿 ≥ 3 年和/或 4 年的长期安全性和耐受性，提示托莫西汀不影响患儿的生长速率。[33]
总的来讲，托莫西汀可以有效改善 ADHD 患儿的 ADHD 核心症状、功能结局和生活质量。临床医生在首次处方托莫西汀时应与患儿及家属充分沟通，帮助其设定正确的期望值，鼓励患儿长期坚持用药，最终获得成功治疗结局。托莫西汀可有效改善共病 ODD、抽动、焦虑、广泛性发育障碍等 ADHD 患者的核心症状和某些共病症状，并且对 ADHD 患儿生长发育无显著影响，是 ADHD 治疗的一线药物选择。
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