哌甲酯与托莫西汀治疗注意缺陷多动障碍的多维疗效比较：一项12周随机对照试验

Multidimensional Efficacy between Methylphenidate and Atomoxetine in the Treatment of Attention-Deficit/Hyperactivity Disorder: A 12-Week Randomized Controlled Trial

摘要: 背景：哌甲酯和托莫西汀是目前治疗注意缺陷多动障碍(ADHD)的一线和二线药物，但两者在改善核心症状、执行功能、情绪行为问题及生活质量方面的差异效应尚需进一步验证。本研究旨在系统比较两种药物对中国ADHD患儿的疗效与安全性。方法：采用随机、开放标签、平行分组设计，纳入2025年12月至2026年4月于西南康复医院门诊就诊的ADHD患儿120例，随机分配至哌甲酯组(n = 60)和托莫西汀组(n = 60)，分别接受12周治疗。主要结局指标为SNAP-IV量表评分变化，次要结局包括Conners父母症状问卷(PSQ)、IVA-CPT持续操作测验、威斯康星卡片分类测验(WCST)、数字广度测验(DST)、儿童生活质量量表(PedsQL)及不良反应。采用意向性治疗原则分析。结果：治疗后两组SNAP-IV总分均显著下降(哌甲酯组：−10.2 ± 3.5；托莫西汀组：−9.1 ± 3.8，组间P = 0.09)。哌甲酯组在多动/冲动分量表(−5.3 ± 2.1 vs. −3.9 ± 2.4, P = 0.003)、IVA-CPT注意商数(+18.6 ± 12.3 vs. +12.4 ± 11.7, P = 0.01)及WCST持续性错误数(−12.5 ± 8.6 vs. −7.8 ± 7.9, P = 0.004)方面改善更优。托莫西汀组在PSQ焦虑分量表(−3.1 ± 2.2 vs. −1.2 ± 1.9, P < 0.001)及PedsQL情绪功能维度(+12.5 ± 10.1 vs. +6.8 ± 9.4, P = 0.003)方面改善更优。不良反应：哌甲酯组食欲下降(26.7% vs. 16.7%, P = 0.18)和失眠(20.0% vs. 5.0%, P = 0.01)更常见；托莫西汀组嗜睡(21.7% vs. 6.7%, P = 0.02)和恶心(15.0% vs. 5.0%, P = 0.07)更常见。结论：哌甲酯和托莫西汀均能有效改善ADHD核心症状。哌甲酯对多动/冲动及执行功能的改善更具优势，而托莫西汀在缓解焦虑情绪及改善生活质量方面表现更佳。临床选择应基于患儿的症状特征和共病情况。

Abstract: Background: Methylphenidate and atomoxetine are first-line and second-line pharmacotherapies for attention-deficit/hyperactivity disorder (ADHD), but their differential effects on core symptoms, executive functions, emotional and behavioral problems, and quality of life require further validation. This study aimed to systematically compare the efficacy and safety of the two medications in Chinese children with ADHD. Methods: A randomized, open-label, parallel-group design was employed. One hundred twenty children with ADHD attending the outpatient clinic of Southwest Rehabilitation hospital between December 2025 and April 2026 were randomly assigned to methylphenidate group (n = 60) or atomoxetine group (n = 60) for 12 weeks of treatment. The primary outcome was change in SNAP-IV total score. Secondary outcomes included Conners Parent Symptom Questionnaire (PSQ), Integrated Visual and Auditory Continuous Performance Test (IVA-CPT), Wisconsin Card Sorting Test (WCST), Digit Span Test (DST), Pediatric Quality of Life Inventory (PedsQL), and adverse events. Intention-to-treat analysis was applied. Results: Both groups showed significant reductions in SNAP-IV total scores (methylphenidate: −10.2 ± 3.5; atomoxetine: −9.1 ± 3.8; between-group P = 0.09). Methylphenidate demonstrated superior improvements in hyperactivity/impulsivity subscale (−5.3 ± 2.1 vs. −3.9 ± 2.4, P = 0.003), IVA-CPT attention quotient (+18.6 ± 12.3 vs. +12.4 ± 11.7, P = 0.01), and WCST perseverative errors (−12.5 ± 8.6 vs. −7.8 ± 7.9, P = 0.004). Atomoxetine showed greater improvements in PSQ anxiety subscale (−3.1 ± 2.2 vs. −1.2 ± 1.9, P < 0.001) and PedsQL emotional functioning domain (+12.5 ± 10.1 vs. +6.8 ± 9.4, P = 0.003). Adverse events: decreased appetite (26.7% vs. 16.7%, P = 0.18) and insomnia (20.0% vs. 5.0%, P = 0.01) were more common with methylphenidate; somnolence (21.7% vs. 6.7%, P = 0.02) and nausea (15.0% vs. 5.0%, P = 0.07) were more common with atomoxetine. Conclusions: Both methylphenidate and atomoxetine effectively improve core ADHD symptoms. Methylphenidate offers advantages in reducing hyperactivity/impulsivity and enhancing executive functions, while atomoxetine shows superior effects on anxiety symptoms and quality of life. Clinical selection should be guided by the child’s symptom profile and comorbidities.