Journal of the American Academy of Child and Adolescent Psychiatry ( IF 13.3 ) Pub Date : 2022-08-10 , DOI: 10.1016/j.jaac.2022.08.001 Giorgia Michelini 1 , Agatha Lenartowicz 2 , Juan Diego Vera 2 , Robert M Bilder 2 , James J McGough 2 , James T McCracken 2 , Sandra K Loo 2
Objective
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.
Method
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.
Results
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 (R2= 0.34-0.41) as clinical measures alone (R2 = 0.14-.21).
Conclusion
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.
Clinical trial registration information
Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder; https://clinicaltrials.gov; NCT00429273
中文翻译:
哌甲酯、胍法辛和注意力缺陷/多动障碍儿童联合治疗结果的电生理学和临床预测因子
客观的
d-哌醋甲酯和胍法辛(一种 α-2A 激动剂)的组合已成为注意力缺陷/多动障碍 (ADHD) 儿童单一疗法的潜在替代品,但尚不清楚是什么预测了对这些治疗的反应。这项研究首次调查了治疗前临床和脑电图 (EEG) 概况作为随机分配给这些不同药物的儿童治疗结果的预测指标。
方法
共有 181 名 ADHD 儿童(7-14 岁;123 名男孩)完成了一项为期 8 周的随机、双盲、比较研究,使用 d-哌醋甲酯、胍法辛或联合治疗。治疗前评估包括对多动症、焦虑和对立行为的评级。在具有编码、维护和检索阶段的空间工作记忆任务期间,测量了来自位于中额叶和中枕叶区域的皮质来源的脑电图活动。分析测试了治疗前的临床和脑电图测量是否预测了 ADHD 严重程度的治疗相关变化。
结果
更高的治疗前多动冲动和对立症状以及更低的焦虑预示着所有药物组的 ADHD 改善更大。治疗前事件相关的中额叶β功率预测了联合治疗和单一治疗的治疗结果,尽管方向不同。较弱的 β 调节预测联合治疗的改善,而编码和检索期间较强的调节分别预测 d-哌醋甲酯和胍法辛的改善。包括脑电图和临床测量在内的多变量模型解释了使用胍法辛和联合治疗( R 2 = 0.34-0.41)改善 ADHD 的方差是单独使用临床测量(R 2 = 0.14-.21)的两倍。
结论
我们确定了 ADHD 儿童对不同药物疗法反应的治疗特异性和共同预测因子。如果被复制,这些发现将表明,从临床和大脑测量中收集信息可能有助于 ADHD 的个性化治疗决策。
临床试验注册信息
注意力缺陷多动障碍儿童的单一药物与联合药物治疗;https://clinicaltrials.gov;NCT00429273