Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, United Kingdom; School of Biological & Behavioural Sciences, Queen Mary University of London, United Kingdom.
Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, United Kingdom.
J Am Acad Child Adolesc Psychiatry. 2023 Apr;62(4):415-426. doi: 10.1016/j.jaac.2022.08.001. Epub 2022 Aug 10.
The combination of d-methylphenidate and guanfacine (an α-2A agonist) has emerged as a potential alternative to either monotherapy in children with attention-deficit/hyperactivity disorder (ADHD), but it is unclear what predicts response to these treatments. This study is the first to investigate pretreatment clinical and electroencephalography (EEG) profiles as predictors of treatment outcome in children randomized to these different medications.
A total of 181 children with ADHD (aged 7-14 years; 123 boys) completed an 8-week randomized, double-blind, comparative study with d-methylphenidate, guanfacine, or combined treatments. Pretreatment assessments included ratings on ADHD, anxiety, and oppositional behavior. EEG activity from cortical sources localized within midfrontal and midoccipital regions was measured during a spatial working memory task with encoding, maintenance, and retrieval phases. Analyses tested whether pretreatment clinical and EEG measures predicted treatment-related change in ADHD severity.
Higher pretreatment hyperactivity-impulsivity and oppositional symptoms and lower anxiety predicted greater ADHD improvements across all medication groups. Pretreatment event-related midfrontal beta power predicted treatment outcome with combined and monotherapy treatments, albeit in different directions. Weaker beta modulations predicted improvements with combined treatment, whereas stronger modulation during encoding and retrieval predicted improvements with d-methylphenidate and guanfacine, respectively. A multivariate model including EEG and clinical measures explained twice as much variance in ADHD improvement with guanfacine and combined treatment (R= 0.34-0.41) as clinical measures alone (R = 0.14-.21).
We identified treatment-specific and shared predictors of response to different pharmacotherapies in children with ADHD. If replicated, these findings would suggest that aggregating information from clinical and brain measures may aid personalized treatment decisions in ADHD.
Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder; https://clinicaltrials.gov; NCT00429273.
哌醋甲酯和胍法辛（一种 α-2A 激动剂）联合治疗已成为儿童注意力缺陷多动障碍（ADHD）的一种潜在替代治疗方法，但目前尚不清楚哪些因素可以预测这些治疗的反应。本研究首次探讨了接受不同药物治疗的儿童的治疗前临床和脑电图（EEG）特征作为治疗结果的预测因素。
共 181 名患有 ADHD 的儿童（年龄 7-14 岁；123 名男孩）完成了一项为期 8 周的随机、双盲、对照研究，分别接受哌醋甲酯、胍法辛或联合治疗。治疗前评估包括 ADHD、焦虑和对立行为的评分。在空间工作记忆任务中，使用皮质源的 EEG 活动，该任务具有编码、维持和检索阶段。分析测试了治疗前的临床和脑电图测量是否可以预测 ADHD 严重程度的治疗相关变化。
更高的治疗前多动冲动和对立症状以及更低的焦虑预测了所有药物治疗组的 ADHD 改善。治疗前与事件相关的前额叶β功率预测了联合治疗和单药治疗的治疗结果，但方向不同。较弱的β调制预示着联合治疗的改善，而在编码和检索期间更强的调制则预示着哌醋甲酯和胍法辛的改善。包括 EEG 和临床测量的多变量模型解释了胍法辛和联合治疗（R=0.34-0.41）的 ADHD 改善比仅临床测量（R=0.14-0.21）多两倍。
我们确定了 ADHD 儿童对不同药物治疗反应的治疗特异性和共享预测因素。如果得到复制，这些发现将表明从临床和大脑测量中综合信息可能有助于 ADHD 的个性化治疗决策。
儿童注意力缺陷多动障碍的单一与联合药物治疗；https://clinicaltrials.gov；NCT00429273。
