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遗传因素对儿童注意力缺陷/多动障碍药物治疗疗效的影响:研究概述与现状

Genetic Influence on Efficacy of Pharmacotherapy for Pediatric Attention-Deficit/Hyperactivity Disorder: Overview and Current Status of Research.

作者信息

Elsayed Nada A, Yamamoto Kaila M, Froehlich Tanya E

机构信息

Division of Developmental and Behavioral Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, MLC 4002, Cincinnati, OH, 45229, USA.

Department of Gynecology and Obstetrics, Integrated Research Center for Fetal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

出版信息

CNS Drugs. 2020 Apr;34(4):389-414. doi: 10.1007/s40263-020-00702-y.

Abstract

Multiple stimulant and non-stimulant medications are approved for the treatment of attention-deficit/hyperactivity disorder (ADHD), one of the most prevalent childhood neurodevelopmental disorders. Choosing among the available agents and determining the most effective ADHD medication for a given child can be a time-consuming process due to the high inter-individual variability in treatment efficacy. As a result, there is growing interest in identifying predictors of ADHD medication response in children through the burgeoning field of pharmacogenomics. This article reviews childhood ADHD pharmacogenomics efficacy studies published during the last decade (2009-2019), which have largely focused on pharmacodynamic candidate gene investigations of methylphenidate and atomoxetine response, with a smaller number investigating pharmacokinetic candidate genes and genome-wide approaches. Findings from studies which have advanced the field of ADHD pharmacogenomics through investigation of meta-analytic approaches and gene-gene interactions are also overviewed. Despite recent progress, no one genetic variant or currently available pharmacogenomics test has demonstrated clinical utility in pinpointing the optimal ADHD medication for a given individual patient, highlighting the need for further investigation.

摘要

多种兴奋剂和非兴奋剂药物被批准用于治疗注意力缺陷多动障碍(ADHD),这是最常见的儿童神经发育障碍之一。由于治疗效果存在高度个体差异,在现有药物中进行选择并为特定儿童确定最有效的ADHD药物可能是一个耗时的过程。因此,通过新兴的药物基因组学领域来识别儿童ADHD药物反应预测指标的兴趣日益浓厚。本文回顾了过去十年(2009 - 2019年)发表的儿童ADHD药物基因组学疗效研究,这些研究主要集中在哌甲酯和托莫西汀反应的药效学候选基因研究,较少数量的研究涉及药代动力学候选基因和全基因组方法。还概述了通过荟萃分析方法和基因 - 基因相互作用研究推动ADHD药物基因组学领域发展的研究结果。尽管最近取得了进展,但没有一个基因变异或目前可用的药物基因组学检测在为特定个体患者确定最佳ADHD药物方面显示出临床实用性,这突出了进一步研究的必要性。

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