抗精神病药物的疗效不足和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结果之间关联的证据,包括抗精神病药物反应,抗精神病药引起的体重/BMI增加,代谢综合征,抗精神病药相关催乳素水平,抗精神病药引起的迟发性运动障碍(TD),氯氮平诱导的粒细胞缺乏症(CLA),和SSD患者的药物浓度水平(药代动力学)。通过2010-2022年的深入系统搜索,我们确定了501条记录。我们纳入了29个荟萃分析,构成来自298个原始研究的汇总数据,涉及39个基因的69个PGx变体,CYP2D9的4个代谢表型和CYP2C19的3个代谢表型。Weobservedweakunadjustednominalsignificant(p<0.05)additionaleffectsofPGxvariantsofDRD1,DRD2,DRD3,HTR1A,HTR2A,HTR3A,和COMT(10种变体)对抗精神病药反应的影响;DRD2,HTR2C,BDNF,ADRA2A,ADRB3,GNB3,INSIG2,LEP,MC4R,体重增加和SNAP25(14种变体);代谢综合征的HTR2C(一种变体);催乳素水平的DRD2(一种变体);TD上的COMT和BDNF(两种变体);CLA上的HLA-DRB1(一种变体);抗精神病药血浆水平上的CYP2D6(四种表型)和CYP2C19(两种表型)。在未来,在临床实践中建立任何可重复的PGx护照之前,需要精心设计的纵向自然多中心PGx研究,以验证PGx变体在抗精神病药物结局中的有效性.
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 CYP2D9, and 3 of CYP2C19. We observed weak unadjusted nominal significant (p < 0.05) additive effects of PGx variants of DRD1, DRD2, DRD3, HTR1A, HTR2A, HTR3A, and COMT (10 variants) on antipsychotic response; DRD2, HTR2C, BDNF, ADRA2A, ADRB3, GNB3, INSIG2, LEP, MC4R, and SNAP25 (14 variants) on weight gain; HTR2C (one variant) on metabolic syndrome; DRD2 (one variant) on prolactin levels; COMT and BDNF (two variants) on TD; HLA-DRB1 (one variant) on CLA; CYP2D6 (four phenotypes) and CYP2C19 (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.