Merino Diane, Fernandez Arnaud, Gérard Alexandre O, Ben Othman Nouha, Rocher Fanny, Askenazy Florence, Verstuyft Céline, Drici Milou-Daniel, Thümmler Susanne
Department of Child and Adolescent Psychiatry, Children's Hospitals of Nice CHU-Lenval, 06200 Nice, France.
CoBTek Laboratory, Université Côte d'Azur, 06100 Nice, France.
Pharmaceuticals (Basel). 2022 Jun 14;15(6):749. doi: 10.3390/ph15060749.
Children and youth treated with antipsychotic drugs (APs) are particularly vulnerable to adverse drug reactions (ADRs) and prone to poor treatment response. In particular, interindividual variations in drug exposure can result from differential metabolism of APs by cytochromes, subject to genetic polymorphism. is pivotal in the metabolism of the APs olanzapine, clozapine, and loxapine, whose safety profile warrants caution. We aimed to shed some light on the pharmacogenetic profiles possibly associated with these drugs' ADRs and loss of efficacy in children and youth. We conducted a systematic review relying on four databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 recommendations and checklist, with a quality assessment. Our research yielded 32 publications. The most frequent ADRs were weight gain and metabolic syndrome (18; 56.3%), followed by lack of therapeutic effect (8; 25%) and neurological ADRs (7; 21.8%). The overall mean quality score was 11.3/24 (±2.7). In 11 studies (34.3%), genotyping focused on the study of cytochromes. Findings regarding possible associations were sometimes conflicting. Nonetheless, cases of major clinical improvement were fostered by genotyping. Yet, remains poorly investigated. Further studies are required to improve the assessment of the risk-benefit balance of prescription for children and youth treated with olanzapine, clozapine, and/or loxapine.
接受抗精神病药物（APs）治疗的儿童和青少年特别容易出现药物不良反应（ADRs），且治疗反应往往不佳。特别是，药物暴露的个体差异可能源于细胞色素对APs的代谢差异，这受基因多态性影响。细胞色素在奥氮平、氯氮平和洛沙平这些APs的代谢中起关键作用，其安全性值得关注。我们旨在阐明可能与这些药物在儿童和青少年中出现的ADRs及疗效丧失相关的药物遗传学特征。我们依据四个数据库进行了系统评价，遵循系统评价和Meta分析的首选报告项目（PRISMA）2020推荐意见和清单，并进行了质量评估。我们的研究得到了32篇出版物。最常见的ADRs是体重增加和代谢综合征（18例；56.3%），其次是治疗效果不佳（8例；25%）和神经学ADRs（7例；21.8%）。总体平均质量评分为11.3/24（±2.7）。在11项研究（34.3%）中，基因分型专注于细胞色素的研究。关于可能关联的研究结果有时相互矛盾。尽管如此，基因分型促进了主要临床改善的病例。然而，细胞色素仍研究不足。需要进一步研究以改善对接受奥氮平、氯氮平和/或洛沙平治疗的儿童和青少年处方风险效益平衡的评估。
