Teng Yuxin, Sandhu Amrit, Liemburg Edith J, Naderi Elnaz, Alizadeh Behrooz Z
Department of Epidemiology, University Medical Centre Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
Department of Psychiatry, Rob Giel Research Center, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
J Pers Med. 2023 Mar 4;13(3):471. doi: 10.3390/jpm13030471.
The inadequate efficacy and adverse effects of antipsychotics severely affect the recovery of patients with schizophrenia spectrum disorders (SSD). We report the evidence for associations between pharmacogenetic (PGx) variants and antipsychotics outcomes, including antipsychotic response, antipsychotic-induced weight/BMI gain, metabolic syndrome, antipsychotic-related prolactin levels, antipsychotic-induced tardive dyskinesia (TD), clozapine-induced agranulocytosis (CLA), and drug concentration level (pharmacokinetics) in SSD patients. Through an in-depth systematic search in 2010-2022, we identified 501 records. We included 29 meta-analyses constituting pooled data from 298 original studies over 69 PGx variants across 39 genes, 4 metabolizing phenotypes of , and 3 of . We observed weak unadjusted nominal significant ( < 0.05) additive effects of PGx variants of , , , , , , and (10 variants) on antipsychotic response; , , , , , , , , , and (14 variants) on weight gain; (one variant) on metabolic syndrome; (one variant) on prolactin levels; and (two variants) on TD; HLA-DRB1 (one variant) on CLA; (four phenotypes) and (two phenotypes) on antipsychotics plasma levels. In the future, well-designed longitudinal naturalistic multi-center PGx studies are needed to validate the effectiveness of PGx variants in antipsychotic outcomes before establishing any reproducible PGx passport in clinical practice.
抗精神病药物疗效不佳及不良反应严重影响精神分裂症谱系障碍（SSD）患者的康复。我们报告了药物遗传学（PGx）变异与抗精神病药物治疗结果之间关联的证据，这些结果包括抗精神病药物反应、抗精神病药物引起的体重/体重指数增加、代谢综合征、抗精神病药物相关催乳素水平、抗精神病药物引起的迟发性运动障碍（TD）、氯氮平引起的粒细胞缺乏症（CLA）以及SSD患者的药物浓度水平（药代动力学）。通过对2010 - 2022年进行的深入系统检索，我们识别出501条记录。我们纳入了29项荟萃分析，这些荟萃分析汇总了来自298项原始研究的数据，涉及39个基因的69个PGx变异、4种代谢表型以及3种其他情况。我们观察到，在未调整的情况下，某些PGx变异（如[具体基因1]、[具体基因2]等共10个变异）对抗精神病药物反应有微弱的名义显著（<0.05）加性效应；[具体基因3]、[具体基因4]等共14个变异对体重增加有影响；[具体基因5]（1个变异）对代谢综合征有影响；[具体基因6]（1个变异）对催乳素水平有影响；[具体基因7]和[具体基因8]（2个变异）对TD有影响；HLA - DRB1（1个变异）对CLA有影响；[具体基因9]（4种表型）和[具体基因10]（2种表型）对抗精神病药物血浆水平有影响。未来，在临床实践中建立任何可重复的PGx档案之前，需要精心设计的纵向自然主义多中心PGx研究来验证PGx变异在抗精神病药物治疗结果中的有效性。
