Kobylecki Camilla J, Hansen Thomas, Timm Sally, Wang August, Jakobsen Klaus D, Sørensen Holger J, Rasmussen Henrik B, Werge Thomas
Research Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, Roskilde, Denmark.
Ther Drug Monit. 2008 Jun;30(3):265-70. doi: 10.1097/FTD.0b013e31817721d6.
Suicidal behavior and substance abuse are frequent phenomena among patients with schizophrenia and may be attributable in part to antipsychotic treatment failure. Individuals who carry functional variants of the CYP2D6 and CYP2C19 genes, shown to cause altered drug metabolism of psychoactive drugs, are at risk of toxic accumulation or rapid elimination of these drugs, leading to treatment failure. We tested whether substance abuse disorder and suicidal behavior were associated with the CYP2D6 and CYP2C19 genotypes among patients with schizophrenia. Three hundred sixty-two patients with schizophrenia spectrum disorders (International Classification of Diseases, 10th Revision) were genotyped for functional CYP2D6 and CYP2C19 polymorphisms. Based on available medical records and clinical interviews, their suicidal behavior and substance abuse disorder were evaluated. No significant associations between the CYP2D6 and CYP2C19 genotypes and suicidal behavior or substance abuse disorder were noted, and we conclude that cytochrome P450 genotyping in its present form is clinically irrelevant with respect to these phenomena.
自杀行为和物质滥用在精神分裂症患者中很常见,部分原因可能是抗精神病药物治疗失败。携带CYP2D6和CYP2C19基因功能变异的个体,已证明这些变异会导致精神活性药物的药物代谢改变,存在这些药物毒性蓄积或快速消除的风险,从而导致治疗失败。我们测试了物质滥用障碍和自杀行为是否与精神分裂症患者的CYP2D6和CYP2C19基因型相关。对362例精神分裂症谱系障碍患者(国际疾病分类第10版)进行了CYP2D6和CYP2C19功能多态性基因分型。根据现有的医疗记录和临床访谈,对他们的自杀行为和物质滥用障碍进行了评估。未发现CYP2D6和CYP2C19基因型与自杀行为或物质滥用障碍之间存在显著关联,我们得出结论,就这些现象而言,目前形式的细胞色素P450基因分型在临床上并无关联。