Abstract：
Objectives: Stimulants, such as methylphenidate (MPH) and amphetamines, represent the first-line pharmacological option for attention-deficit/hyperactivity disorder (ADHD). Randomized controlled trials (RCTs) have demonstrated beneficial effects at a group level but could not identify characteristics consistently associated with varying individual response. Thus, more individualized approaches are needed. Experimental studies have suggested that the neurobiological response to a single dose is indicative of longer term response. It is unclear whether this also applies to clinical measures. Methods: We carried out a systematic review of RCTs testing the association between the clinical response to a single dose of stimulants and longer term improvement. Potentially suitable single-dose RCTs were identified from the MED-ADHD data set, the European ADHD Guidelines Group RCT Data set (https://med-adhd.org/), as updated on February 1, 2024. Quality assessment was carried out using the Cochrane Risk of Bias (RoB) 2.0 tool. Results: A total of 63 single-dose RCTs (94% testing MPH, 85% in children) were identified. Among these, only a secondary analysis of an RCT tested the association between acute and longer term clinical response. This showed that the clinical improvement after a single dose of MPH was significantly associated with symptom improvement after a 4-week MPH treatment in 46 children (89% males) with ADHD. The risk of bias was rated as moderate. A further RCT used near-infrared spectroscopy, thus did not meet the inclusion criteria, and reported an association between brain changes under a single-dose and longer term clinical response in 22 children (82% males) with ADHD. The remaining RCTs only reported single-dose effects on neuropsychological, neuroimaging, or neurophysiological measures. Conclusion: This systematic review highlighted an important gap in the current knowledge. Investigating how acute and long-term response may be related can foster our understanding of stimulant mechanism of action and help develop stratification approaches for more tailored treatment strategies. Future studies need to investigate potential age- and sex-related differences.
摘要：
目标：兴奋剂，例如哌醋甲酯（MPH）和苯丙胺，代表注意力缺陷/多动障碍（ADHD）的一线药物选择。随机对照试验（RCTs）已在组水平上证明了有益的效果，但无法确定与不同个体反应一致相关的特征。因此，需要更多的个性化方法。实验研究表明,对单剂量的神经生物学反应指示长期反应。目前尚不清楚这是否也适用于临床措施。方法：我们对RCTs进行了系统评价，以测试单剂量兴奋剂的临床反应与长期改善之间的关系。从MED-ADHD数据集中确定了可能合适的单剂量随机对照试验，欧洲ADHD指南组RCT数据集（https://med-adhd.org/），于2024年2月1日更新。使用Cochrane偏差风险（RoB）2.0工具进行质量评估。结果：总共63例单剂量随机对照试验(94%检测MPH，85%的儿童）被确认。其中,只有RCT的二次分析检验了急性和长期临床反应之间的相关性.这表明，在46名患有ADHD的儿童（89％的男性）中，单剂量MPH后的临床改善与4周MPH治疗后的症状改善显着相关。偏倚风险被评为中度。另一个RCT使用近红外光谱，因此不符合纳入标准，报告了22名患有ADHD的儿童(82%为男性)单剂量下的大脑变化与长期临床反应之间的关联。其余的随机对照试验仅报道了单剂量对神经心理学的影响，神经影像学,或神经生理学措施。结论：本系统综述强调了当前知识的重要差距。研究急性和长期反应可能与之相关，可以促进我们对兴奋剂作用机制的理解，并有助于开发分层方法以制定更量身定制的治疗策略。未来的研究需要调查潜在的年龄和性别相关的差异。
