Verstegen Ruud H J, Cohn Iris, Feldman Mark E, Gorman Daniel, Ito Shinya
Canadian Paediatric Society, Drug Therapy Committee, Ottawa, Ontario, Canada.
Paediatr Child Health. 2024 Sep 13;29(5):311-323. doi: 10.1093/pch/pxae029. eCollection 2024 Aug.
Psychoactive medications are increasingly used to treat children and youth with mental health conditions, but individual variations in response highlight the need for precision medicine. Pharmacogenetic (PGx) testing is a key component of precision medicine. The number of commercial pharmacogenetic testing companies promoting PGx, with the promise of achieving individualized and effective treatment of mental health conditions, has grown exponentially in recent years. Scientific evidence supporting the use of PGx to manage mental health conditions is limited, especially for paediatric populations. This practice point outlines steps guiding the use and interpretation of PGx testing for psychoactive medications in clinical settings, along with key supportive resources. Practice guidelines have been developed for variants in pharmacogenes encoding cytochrome P450 drug-metabolizing enzymes (e.g., , , ) as one determinant of drug concentrations in blood, which can support both drug choice and dosing strategy for certain anti-psychotics, anti-depressants, and anti-epileptics. Adverse drug reactions to some anti-epileptic drugs (e.g., carbamazepine and phenytoin) have been associated with certain human leukocyte antigen types and variants in DNA polymerase gamma (; valproic acid). Evidence remains limited for genetic variants of drug target proteins, making it challenging to identify patients with altered treatment responses at a therapeutic blood concentration.
精神活性药物越来越多地用于治疗患有精神健康问题的儿童和青少年,但个体反应差异凸显了精准医学的必要性。药物遗传学(PGx)检测是精准医学的关键组成部分。近年来,宣传PGx检测的商业公司数量呈指数级增长,它们承诺能够实现对精神健康问题的个体化有效治疗。支持使用PGx检测来管理精神健康问题的科学证据有限,尤其是针对儿科人群。本实践要点概述了在临床环境中指导使用和解读精神活性药物PGx检测的步骤,以及关键的支持资源。针对编码细胞色素P450药物代谢酶(如 、 、 )的药物基因变体,已经制定了实践指南,这些变体是血液中药物浓度的一个决定因素,可支持某些抗精神病药物、抗抑郁药物和抗癫痫药物的药物选择和给药策略。对某些抗癫痫药物(如卡马西平和苯妥英)的药物不良反应与特定的人类白细胞抗原类型以及DNA聚合酶γ( ;丙戊酸)的变体有关。关于药物靶蛋白基因变体的证据仍然有限,这使得在治疗血药浓度下识别治疗反应改变的患者具有挑战性。