Pan Pei-Yin, Yeh Chin-Bin
Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
J Clin Psychopharmacol. 2025;45(4):356-363. doi: 10.1097/JCP.0000000000002002. Epub 2025 Apr 16.
In this study, we examined the effectiveness of methylphenidate on emotion dysregulation among children with attention-deficit/hyperactivity disorder (ADHD), and the strategy of switching to or adding aripiprazole for nonresponders.
We conducted a 3-step, 10-week, open-label trial including children (6-18 years old) with ADHD and emotion dysregulation, defined according to the Child Behavior Checklist-Dysregulation Profile. In step 1, patients received methylphenidate treatment for 4 weeks. In step 2, nonresponders were started on aripiprazole treatment for 4 weeks. Nonresponders in step 2 entered step 3, receiving a combination of methylphenidate and aripiprazole for 2 weeks. The primary outcome was the change from baseline in emotion dysregulation, assessed using the irritability subscale of the Aberrant Behavior Checklist. Secondary outcomes included the change from baseline in ADHD symptoms, cross-domain-associated symptoms, adaptive functioning, and neurocognitive profiles.
Among the 30 enrolled patients, 22 (73.3%) responded to methylphenidate (group MR), while 8 entered step 2 (aripiprazole treatment for methylphenidate nonresponders; group MN). In step 2, 5 patients responded to aripiprazole, while 2 patients entered step 3 and received methylphenidate plus aripiprazole. Patients who responded to methylphenidate or aripiprazole exhibited significant improvements in emotion dysregulation (Hedges' g: 2.62 and 1.30, respectively) and school adaptation. Emotion dysregulation severity was correlated with oppositional defiant disorder symptoms, but not with core symptoms of ADHD.
The nature of emotion dysregulation in ADHD is heterogeneous regarding the response to methylphenidate. For most patients, methylphenidate significantly improved emotion dysregulation. Aripiprazole could be effective and safe for methylphenidate nonresponders.
在本研究中，我们考察了哌甲酯对注意力缺陷多动障碍（ADHD）儿童情绪调节障碍的疗效，以及对无反应者换用或加用阿立哌唑的策略。
我们进行了一项为期10周的三阶段开放标签试验，纳入了根据儿童行为量表-失调剖面图定义的患有ADHD和情绪调节障碍的6至18岁儿童。在第一阶段，患者接受4周的哌甲酯治疗。在第二阶段，无反应者开始接受4周的阿立哌唑治疗。第二阶段的无反应者进入第三阶段，接受2周的哌甲酯和阿立哌唑联合治疗。主要结局是使用异常行为检查表的易激惹分量表评估的情绪调节障碍相对于基线的变化。次要结局包括ADHD症状、跨领域相关症状、适应性功能和神经认知概况相对于基线的变化。
在30名入组患者中，22名（73.3%）对哌甲酯有反应（MR组），而8名进入第二阶段（对哌甲酯无反应者接受阿立哌唑治疗；MN组）。在第二阶段，5名患者对阿立哌唑有反应，而2名患者进入第三阶段并接受哌甲酯加阿立哌唑治疗。对哌甲酯或阿立哌唑有反应的患者在情绪调节障碍（Hedges' g分别为2.62和1.30）和学校适应方面有显著改善。情绪调节障碍的严重程度与对立违抗障碍症状相关，但与ADHD的核心症状无关。
ADHD中情绪调节障碍的性质在对哌甲酯的反应方面是异质性的。对于大多数患者，哌甲酯显著改善了情绪调节障碍。阿立哌唑对哌甲酯无反应者可能有效且安全。
