Chang Florence Cf, Fung Victor Sc
Movement Disorders Unit, Department of Neurology, Westmead Hospital, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
Pharmgenomics Pers Med. 2014 Oct 13;7:317-28. doi: 10.2147/PGPM.S52806. eCollection 2014.
Pharmacogenomics is the study of the effects of genetic polymorphisms on medication pharmacokinetics and pharmacodynamics. It offers advantages in predicting drug efficacy and/or toxicity and has already changed clinical practice in many fields of medicine. Tardive dyskinesia (TD) is a movement disorder that rarely remits and poses significant social stigma and physical discomfort for the patient. Pharmacokinetic studies show an association between cytochrome P450 enzyme-determined poor metabolizer status and elevated serum antipsychotic and metabolite levels. However, few prospective studies have shown this to correlate with the occurrence of TD. Many retrospective, case-control and cross-sectional studies have examined the association of cytochrome P450 enzyme, dopamine (receptor, metabolizer and transporter), serotonin (receptor and transporter), and oxidative stress enzyme gene polymorphisms with the occurrence and severity of TD. These studies have produced conflicting and confusing results secondary to heterogeneous inclusion criteria and other patient characteristics that also act as confounding factors. This paper aims to review and summarize the pharmacogenetic findings in antipsychotic-associated TD and assess its clinical significance for psychiatry patients. In addition, we hope to provide insight into areas that need further research.
药物基因组学是研究基因多态性对药物药代动力学和药效学的影响。它在预测药物疗效和/或毒性方面具有优势,并且已经改变了许多医学领域的临床实践。迟发性运动障碍(TD)是一种运动障碍,很少缓解,给患者带来严重的社会耻辱感和身体不适。药代动力学研究表明,细胞色素P450酶决定的代谢不良状态与血清抗精神病药物和代谢物水平升高之间存在关联。然而,很少有前瞻性研究表明这与TD的发生相关。许多回顾性、病例对照和横断面研究已经考察了细胞色素P450酶、多巴胺(受体、代谢酶和转运体)、5-羟色胺(受体和转运体)以及氧化应激酶基因多态性与TD的发生和严重程度之间的关联。由于纳入标准的异质性以及其他也作为混杂因素的患者特征,这些研究产生了相互矛盾和令人困惑的结果。本文旨在回顾和总结抗精神病药物相关TD的药物遗传学研究结果,并评估其对精神病患者的临床意义。此外,我们希望为需要进一步研究的领域提供见解。