Yoshida Kazunari, Müller Daniel J
Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
Mol Neuropsychiatry. 2020 Apr;5(Suppl 1):1-26. doi: 10.1159/000492332. Epub 2018 Sep 26.
Numerous genetic variants have been shown to be associated with antipsychotic response and adverse effects of schizophrenia treatment. However, the clinical application of these findings is limited. The aim of this narrative review is to summarize the most recent publications and recommendations related to the genetics of antipsychotic treatment and shed light on the clinical utility of pharmacogenetics/pharmacogenomics (PGx). We reviewed the literature on PGx studies with antipsychotic drugs (i.e., antipsychotic response and adverse effects) and commonly used commercial PGx tools for clinical practice. Publications and reviews were included with emphasis on articles published between January 2015 and April 2018. We found 44 studies focusing on antipsychotic response and 45 studies on adverse effects (e.g., antipsychotic-induced weight gain, movement disorders, hormonal abnormality, and clozapine-induced agranulocytosis/granulocytopenia), albeit with mixed results. Overall, several gene variants related to antipsychotic response and adverse effects in the treatment of patients with schizophrenia have been reported, and several commercial pharmacogenomic tests have become available. However, further well-designed investigations and replication studies in large and well-characterized samples are needed to facilitate the application of PGx findings to clinical practice.
大量基因变异已被证明与抗精神病药物反应及精神分裂症治疗的不良反应相关。然而，这些研究结果的临床应用有限。本叙述性综述的目的是总结与抗精神病药物治疗遗传学相关的最新出版物和建议，并阐明药物遗传学/药物基因组学（PGx）的临床应用价值。我们回顾了关于抗精神病药物PGx研究（即抗精神病药物反应和不良反应）以及临床实践中常用的商业PGx工具的文献。纳入的出版物和综述重点是2015年1月至2018年4月期间发表的文章。我们发现44项研究聚焦于抗精神病药物反应，45项研究关注不良反应（如抗精神病药物引起的体重增加、运动障碍、激素异常以及氯氮平引起的粒细胞缺乏症/粒细胞减少症），尽管结果不一。总体而言，已有多项与精神分裂症患者治疗中抗精神病药物反应和不良反应相关的基因变异被报道，并且已有几种商业药物基因组学检测可供使用。然而，需要在大型且特征明确的样本中进行进一步精心设计的研究和重复研究，以促进PGx研究结果在临床实践中的应用。
