Mrazek David A
Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota, USA.
Dialogues Clin Neurosci. 2010;12(1):69-76. doi: 10.31887/DCNS.2010.12.1/dmrazek.
The clinical adoption of psychiatric pharmacogenomic testing has taken place rapidly over the past 7 years. Initially, drug-metabolizing enzyme genes, such as the cytochrome P450 2D6 gene (CYP2D6), were identified. Genotyping the highly variable cytochrome P450 2D6 gene now provides clinicians with the opportunity to identify both poor metabolizers and ultrarapid metabolizers of 2D6 substrate medications. Subsequently, genes influencing the pharmacodynamic response of medications have been made available for clinical practice. Among the earliest "target genes" was the serotonin transporter gene (SLC6A4) which has variants that have been shown to influence the clinical response of patients of European ancestry when they are treated with selective serotonin reuptake inhibitors. Genotyping of some of the serotonin receptor genes is also available to guide clinical practice. The quantification of the clinical utility of pharmacogenomic testing is evolving, and ethical considerations for testing have been established. Given the increasingly clear cost-effectiveness of genotyping, it has recently been predicted that pharmacogenomic testing will routinely be ordered to guide the selection and dosing of psychotropic medications.
在过去7年里,精神科药物基因组检测在临床上的应用迅速发展。最初,人们鉴定出了药物代谢酶基因,如细胞色素P450 2D6基因(CYP2D6)。对高度可变的细胞色素P450 2D6基因进行基因分型,现在为临床医生提供了识别2D6底物药物的慢代谢者和超快代谢者的机会。随后,影响药物药效学反应的基因也已应用于临床实践。最早的“靶基因”之一是血清素转运体基因(SLC6A4),其变体已被证明在欧洲血统患者接受选择性5-羟色胺再摄取抑制剂治疗时会影响临床反应。一些血清素受体基因的基因分型也可用于指导临床实践。药物基因组检测临床效用的量化正在不断发展,并且已经确立了检测的伦理考量。鉴于基因分型的成本效益越来越明显,最近有人预测,药物基因组检测将常规用于指导精神药物的选择和剂量调整。