Cincinnati Children's Hospital Medical Center, Ohio; University of Cincinnati, Ohio.
University of Connecticut School of Medicine, Farmington; Institute of Living/Hartford Hospital, Hartford, Connecticut.
J Am Acad Child Adolesc Psychiatry. 2021 Jun;60(6):660-664. doi: 10.1016/j.jaac.2020.08.006. Epub 2020 Aug 26.
AACAP's recent policy statement on Clinical Use of Pharmacogenetic Tests in Prescribing Psychotropic Medications for Children and Adolescents recommends that "clinicians avoid using pharmacogenetic testing to select psychotropic medications in children and adolescents." We agree that there are limitations to the nascent evidence base for using pharmacogenetics, especially in combinatorial form (eg, test results that bin medications based on multiple genes). However, all-or-nothing recommendations fail to recognize the nuance and context of this testing and contrast with the AACAP Facts for Families on pharmacogenetic testing. Moreover, pharmacogenetic testing may inform dosing for antidepressants that are commonly used in child and adolescent psychiatry (eg, sertraline, escitalopram, citalopram, fluvoxamine) as well as the tolerability of some psychotropic medications. With this in mind, we wish to remind the AACAP community of the accumulating evidence and to highlight important principles of pharmacogenetic testing in youths. Specifically: 1) pharmacogenetic testing is not always performed by commercial companies and is not always combinatorial; 2) dosing recommendations or assessment of risk for severe hypersensitivity reactions are based on pharmacogenetics in the Food and Drug Administration (FDA)-approved product inserts for several medications commonly prescribed to children (eg, citalopram, aripiprazole, atomoxetine, carbamazepine, oxcarbazepine at www.fda.gov/drugs/science-and-research-drugs/table-pharmacogenomic-biomarkers-drug-labeling); 3) expert consensus guidelines for dosing or identifying hypersensitivity risk for these drugs are available from the National Institutes of Health (NIH)-supported Clinical Pharmacogenetics Implementation Consortium (CPIC, www.cpicpgx.org/), which provides transparent, regularly updated, and evidence-based evaluations of pharmacogenetic data; and 4) randomized trials are not required for clinical dose adjustments; for example, dose adjustments because of decreased hepatic function or concomitant interacting medications are based on pharmacokinetic data, similar to many pharmacokinetic gene-based recommendations from CPIC.
美国儿童和青少年精神病学会（AACAP）最近发布的关于在为儿童和青少年开精神药物处方时临床应用药物遗传学检测的政策声明建议“临床医生避免使用药物遗传学检测来选择儿童和青少年的精神药物。”我们同意，在使用药物遗传学，尤其是组合形式（例如，根据多种基因对药物进行分类的测试结果）方面，现有的证据基础存在局限性。然而，一刀切的建议未能认识到这种检测的细微差别和背景，与 AACAP 关于药物遗传学检测的《家庭事实》形成对比。此外，药物遗传学检测可能会为儿童和青少年精神病学中常用的抗抑郁药（例如，舍曲林、依地普仑、西酞普兰、氟伏沙明）以及一些精神药物的耐受性提供剂量信息。考虑到这一点，我们希望提醒 AACAP 社区注意不断积累的证据，并强调在年轻人中进行药物遗传学检测的重要原则。具体来说：1）并非所有的药物遗传学检测都是由商业公司进行的，也并非总是组合形式的；2）在食品和药物管理局（FDA）批准的几种常用于儿童的药物的产品说明书中，基于药物遗传学的剂量建议或严重过敏反应风险评估（例如，西酞普兰、阿立哌唑、托莫西汀、卡马西平、奥卡西平，可在 www.fda.gov/drugs/science-and-research-drugs/table-pharmacogenomic-biomarkers-drug-labeling 上找到）；3）来自 NIH 支持的临床药物遗传学实施联盟（CPIC，www.cpicpgx.org/）的针对这些药物的剂量或识别过敏风险的专家共识指南，提供了对药物遗传学数据的透明、定期更新和基于证据的评估；4）不需要随机试验即可进行临床剂量调整；例如，由于肝功能下降或同时服用相互作用的药物而进行剂量调整，是基于药代动力学数据，类似于 CPIC 提供的许多基于药代动力学基因的建议。
