Kirnichnaya K A, Sosin D N, Ivanov M V, Mikhaylov V A, Ivashchenko D V, Ershov E E, Taraskina A E, Nasyrova R F, Krupitsky E M
Bekhterev St. Petersburg Psychoneurological Research Institute, St. Petersburg.
Kashchenko St. Petersburg City Psychiatric Hospital #1, St. Petersburg.
Zh Nevrol Psikhiatr Im S S Korsakova. 2015;115(4):113-125. doi: 10.17116/jnevro201511541113-125.
"Typical" antipsychotics remain the wide-prescribed drugs in modern psychiatry. But these drugs are associated with development of extrapyramidal symptoms (EPS). Preventive methods of EPS are actively developed and they concentrate on personalized approach. The method of taking into account genetic characteristics of patient for prescribing of treatment was proven as effective in cardiology, oncology, HIV-medicine. In this review the modern state of pharmacogenetic research of antipsychotic-induced EPS are considered. There are pharmacokinetic and pharmacodynamic factors which impact on adverse effects. Pharmacokinetic factors are the most well-studied to date, these include genetic polymorphisms of genes of cytochrome P450. However, evidence base while does not allow to do the significant prognosis of development of EPS based on genetic testing of CYP2D6 and CYP7A2 polymorphisms. Genes of pharmacodynamics factors, which realize the EPS during antipsychotic treatment, are the wide field for research. In separate part of review research of such systems as dopaminergic, serotonergic, adrenergic, glutamatergic, GABAergic, BDNF were analyzed. The role of oxidative stress factors in the pathogenesis of antipsychotic-induced EPS was enough detailed considered. The system of those factors may be used for personalized risk assessment of antipsychotics' safety in the future. Although there were numerous studies, the pharmacogenetic-based prevention of EPS before prescribing of antipsychotics was not introduced. However, it is possible to distinguish the most perspectives markers for further research. Furthermore, brief review of new candidate genes provides here, but only preliminary results were published. The main problem of the field is the lack of high- quality studies. Moreover, the several results were not replicated in repeat studies. The pharmacogenetic-based research must be standardized by ethnicity of patients. But there is the ethnical misbalance in world literature. These facts explain why the introduction of pharmacogenetic testing for risk assessment of antipsychotic-induced EPS is so difficult to achieve.
“传统”抗精神病药物仍然是现代精神病学中广泛使用的药物。但这些药物与锥体外系症状（EPS）的发生有关。EPS的预防方法正在积极研发，且集中在个性化方法上。在心脏病学、肿瘤学、艾滋病医学中，考虑患者遗传特征来制定治疗方案的方法已被证明是有效的。在本综述中，我们考虑了抗精神病药物所致EPS的药物遗传学研究现状。有一些药代动力学和药效学因素会影响不良反应。药代动力学因素是迄今为止研究最多的，其中包括细胞色素P450基因的遗传多态性。然而，目前的证据基础还不允许基于CYP2D6和CYP7A2多态性的基因检测对EPS的发生做出显著预测。在抗精神病药物治疗期间引发EPS的药效学因素相关基因，是一个广阔的研究领域。在综述的单独部分，分析了多巴胺能、5-羟色胺能、肾上腺素能、谷氨酸能、γ-氨基丁酸能、脑源性神经营养因子等系统相关的研究。氧化应激因素在抗精神病药物所致EPS发病机制中的作用得到了较为详细的探讨。这些因素系统未来可能用于抗精神病药物安全性的个性化风险评估。尽管有大量研究，但在开具抗精神病药物之前基于药物遗传学的EPS预防方法尚未得到应用。然而，有可能区分出最具前景的标志物以供进一步研究。此外，这里简要回顾了新的候选基因，但仅发表了初步结果。该领域的主要问题是缺乏高质量研究。而且，一些结果在重复研究中未能得到验证。基于药物遗传学的研究必须根据患者的种族进行标准化。但世界文献中存在种族失衡现象。这些事实解释了为什么对抗精神病药物所致EPS的风险评估进行药物遗传学检测难以实现。
