Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK.
Pharmacogenomics J. 2011 Feb;11(1):1-14. doi: 10.1038/tpj.2010.73. Epub 2010 Sep 28.
There is wide variability in the response of individuals to standard doses of antipsychotic drugs. It has been suggested that this may be partly explained by differences in the cytochrome P450 (CYP450) enzyme system responsible for metabolizing the drugs. We conducted a systematic review and meta-analyses to consider whether testing for CYP450 single nucleotide polymorphisms in adults starting antipsychotic treatment for schizophrenia predicts and leads to improvements in clinical outcomes. High analytic validity in terms of sensitivity and specificity was seen in studies reporting P450 testing. However, there was limited evidence of the role of CYP2D6 polymorphisms in antipsychotic efficacy, although there was an association between CYP2D6 genotype and extrapyramidal adverse effects. No studies reported on the prospective use of CYP2D6 genotyping tests in clinical practice. In conclusion, evidence of clinical validity and utility of CYP2D6 testing in patients being prescribed antipsychotics is lacking, and thus, routine pharmacogenetic testing prior to antipsychotic prescription cannot be supported at present. Further research is required to improve the evidence base and to generate data on clinical validity and clinical utility.
个体对抗精神病药物标准剂量的反应存在广泛的变异性。有人认为，这可能部分归因于负责代谢药物的细胞色素 P450（CYP450）酶系统的差异。我们进行了系统评价和荟萃分析，以考虑在开始抗精神病治疗的精神分裂症成年患者中检测 CYP450 单核苷酸多态性是否可以预测并导致临床结局的改善。在报告 P450 检测的研究中，其在分析有效性方面具有较高的灵敏度和特异性。然而，尽管 CYP2D6 基因型与锥体外系不良反应之间存在关联，但 CYP2D6 多态性在抗精神病药物疗效中的作用的证据有限。没有研究报告 CYP2D6 基因分型检测在临床实践中的前瞻性应用。总之，在为接受抗精神病药物治疗的患者进行 CYP2D6 检测方面，缺乏临床有效性和实用性的证据，因此目前不能支持在开抗精神病药物之前进行常规的遗传药理学检测。需要进一步的研究来提高证据基础，并生成关于临床有效性和实用性的数据。
