David A, Fernandez A, Menard M-L, Dor E, Leali G, Maria F, Cruzel C, Askenazy F, Verstuyft C, Thümmler S
Service universitaire de psychiatrie de l'enfant et de l'adolescent, hôpitaux pédiatriques de Nice CHU-Lenval, 57, avenue de la Californie, 06200 Nice, France.
Service universitaire de psychiatrie de l'enfant et de l'adolescent, hôpitaux pédiatriques de Nice CHU-Lenval, 57, avenue de la Californie, 06200 Nice, France; Université Côte d'Azur, CoBTek, FRIS, Nice, France.
Encephale. 2021 Jun;47(3):227-234. doi: 10.1016/j.encep.2020.09.010. Epub 2021 Feb 4.
Some patients in child and adolescent psychiatry present resistance to psychotropic drugs, often resulting in polytherapy, an increased risk of adverse events, and more frequent and longer hospitalisation. Psychotropic drugs are mainly metabolised in the liver, in particular by the CYP2D6 subunit of cytochrome P450. Anomalies such as a duplication of the CYP2D6 gene related to an ultra-rapid metaboliser phenotype has been described to be linked to clinical efficacy. However, little research has been done in child and adolescent psychiatry.
A multi-centric cross-sectional study in the southeast of France explored the relation between pharmaco-resistance to psychotropic drugs and the prevalence of duplications or polymorphisms of CYP2D6 associated with an ultra-rapid phenotype in children and adolescents with severe mental health disease.
Twenty-two patients have been included. The presence of an ultra-rapid phenotype concerns one patient in our study. A second patient presents a slow metaboliser phenotype.
This study allows a clinical characterisation of the population of pediatric drug-resistant patients whose severity and the impact of their pathology are major and require long-term care associated with repeated hospitalisations, multiple drug prescriptions and numerous side effects. However, a link between drug resistance to psychotropic drugs and CYP2D6 UFM abnormalities could not be confirmed. An additional pharmacogenetic analysis by a panel of genes applied in the metabolism, transport and action of psychotropic drugs should be considered to answer questions about the resistance and independent effects of CYP2D6.
儿童和青少年精神病学中的一些患者对精神药物存在抵抗性，这常常导致联合用药、不良事件风险增加以及更频繁和更长时间的住院治疗。精神药物主要在肝脏中代谢，特别是通过细胞色素P450的CYP2D6亚基。与超快代谢表型相关的CYP2D6基因重复等异常情况已被描述为与临床疗效有关。然而，在儿童和青少年精神病学方面的研究很少。
在法国东南部进行的一项多中心横断面研究，探讨了患有严重精神疾病的儿童和青少年对精神药物的耐药性与CYP2D6重复或多态性（与超快表型相关）的患病率之间的关系。
共纳入22名患者。在我们的研究中，有一名患者存在超快表型。另一名患者表现为慢代谢表型。
本研究对儿科耐药患者群体进行了临床特征描述，这些患者病情严重，病理影响重大，需要长期护理，伴有反复住院、多种药物处方和众多副作用。然而，无法证实对精神药物的耐药性与CYP2D6超快代谢异常之间的联系。应考虑通过一组应用于精神药物代谢、转运和作用的基因进行额外的药物遗传学分析，以回答有关CYP2D6耐药性和独立作用的问题。
