Grzesiak Magdalena, Beszłej Aleksander, Lebioda Arleta, Jonkisz Anna, Dobosz Tadeusz, Kiejna Andrzej
Katedry i Kliniki Psychiatrii AM we Wrocławiu.
Psychiatr Pol. 2003 May-Jun;37(3):433-44.
The majority of antidepressants undergo the oxidative biotransformation catalysed by cytochrome P-450, particularly by izoenzyme CYP2D6, whose activity is genetically determined. In many cases poor tolerance of antidepressants depends on CYP2D6 activity. The aim of the study was the evaluation of the relationship between the CYP2Dg genotype and the occurrence of side effects during antidepressive pharmacotherapy.
Eighty nine patients were included into study. During the last episode of depression all included patients were treated with antidepressants, whose metabolism is catalysed mainly by CYP2D6. Based on medical records and patient interview the occurrence of side effects was evaluated. The genetic material was isolated from the patients' saliva. Genotyping of CYP2D6 was performed using the PCR techniques. The most frequent inactive alleles in the Caucasian population, *3 and *4 were identified. Alleles that were not identified as *3 or *4 were stated as active allele *1.
Based on retrospective analysis among patients treated with antidepressants during the last episode of depression 42 patients (47.2%) reported severe side effects. Comparing to the group of patients with wide type genotype (*1/*1), in the group with the genotype including at least one inactive allele, side effects occurred significantly more frequently.
In this group, comparing to the group of patients with wide type genotype, severe side effects that required discontinuation of antidepressants also occurred significantly more frequently.
大多数抗抑郁药通过细胞色素P-450催化进行氧化生物转化,特别是由同工酶CYP2D6催化,其活性由基因决定。在许多情况下,抗抑郁药耐受性差取决于CYP2D6的活性。本研究的目的是评估CYP2D6基因型与抗抑郁药物治疗期间副作用发生之间的关系。
89名患者纳入研究。在最近一次抑郁发作期间,所有纳入的患者均接受主要由CYP2D6催化代谢的抗抑郁药治疗。根据病历和患者访谈评估副作用的发生情况。从患者唾液中分离遗传物质。使用PCR技术对CYP2D6进行基因分型。确定了白种人群中最常见的无活性等位基因3和4。未鉴定为3或4的等位基因被视为活性等位基因*1。
基于对上次抑郁发作期间接受抗抑郁药治疗患者的回顾性分析,42名患者(47.2%)报告有严重副作用。与野生型基因型(*1/*1)患者组相比,基因型中至少包含一个无活性等位基因的患者组中,副作用发生频率明显更高。
在该组中,与野生型基因型患者组相比,需要停用抗抑郁药的严重副作用发生频率也明显更高。