药物基因组学检测指导下精神分裂症患者个体化治疗的效果评价

Therapeutic efficacy of pharmacogenomics-guided personalized treatment for patients with schizophrenia

目的探讨药物基因组学(PGx)检测指导精神分裂症患者个体化用药治疗中的效果。方法179例精神分裂症患者分为经验用药组(经验组,n=81;医师用药经验下行抗精神病药物治疗)和个体化用药组(个体组,n=98;治疗前PGx检测结果下行抗精神病药物治疗),均随访观察3个月,收集2组患者入院时的一般临床资料[年龄、居住地、教育程度、婚姻、居住情况、吸烟史、饮酒史、首发年龄、精神障碍家族史、总病程、收缩压、舒张压、心率、体质量、身高、体质量指数(BMI)及腹围等];使用口腔拭子采集个体组患者治疗前的口腔黏膜上皮细胞,提取DNA行PGx检测;抽取2组患者治疗前及治疗后3个月晨起空腹静脉血,采用全自动生化分析仪检测全血血脂[甘油三酯(TG)和胆固醇(CHOL)]、空腹血浆血糖(Glu)及泌乳素(PRL);采用阳性和阴性症状(PANSS)量表、临床总体印象(CGI)量表[包括疗效总评(CGI-GI;治疗前不测定)及病情严重程度总评(CGI-SI)]及个人和社会功能(PSP)量表、功能大体评定(GAF)量表评价治疗前及治疗后3个月2组患者的疗效及社会功能。结果个体组和经验组患者治疗后PANSS量表总分、各因子分及PANSS减分率比较,差异均有统计学意义(P<0.001),表现为个体组<经验组;个体组和经验组患者治疗后CGI-SI及CGI-GI分值比较,差异均有统计学意义(P<0.05),表现为个体组<经验组;个体组和经验组患者治疗后糖脂代谢及PRL指标比较,除PRL外,其余各变量间差异均无统计学意义(P>0.05),表现为个体组患者PRL水平低于经验组(P<0.05);个体组患者治疗后PSP、GAF均分高于经验组,差异均有统计学意义(P<0.001)。结论PGx检测指导用药的个性化治疗方式可有效提高精神分裂症患者抗精神病药物治疗的疗效,减少高PRL血症的发生,改善患者的社会功能。

Objective To evaluate therapeutic efficacy of pharmacogenomics(PGx)-guided personalized treatment for patients with schizophrenia.Methods A total of 179 patients with schizophrenia were divided into an experience medication group(experience group,n=81;physician-guided antipsychotic drugs)and a personalized medication group(individual group,n=98,PGx-guided antipsychotic drugs).Both groups were followed up for 3 months.General clinical data of two groups of patients at admission were collected[age,residence,education level,marriage,residential situation,smoking history,drinking history,age of onset,family history of mental disorders,total disease course,systolic and diastolic blood pressures,heart rate,body mass,height,body mass index(BMI),and abdominal circumference].Oral mucosal epithelial cells were collected from the patients in individual group before treatment using oral swabs to extract DNA for PGx detection.Fasting venous blood from the patients in two groups in the morning was withdrawn before treatment and 3 months after treatment.Automated biochemical analyzer was used to detect whole blood lipids[triglycerides(TG)and cholesterol(CHOL)],fasting plasma glucose(Glu),and prolactin(PRL).The efficacy and social function of the patients in two groups before treatment and 3 months after treatment were evaluated using positive and negative syndrome scale(PANSS),clinical global impression(CGI)scale[including CGI-Global Improvement(CGI-GI,not measured before treatment),CGI-Severity of Illness(CGI-SI)],personal and social performance(PSP)scale and Global Assessment of Functioning(GAF)scale.Results There were statistically significant differences in the total score of PANSS,various factor scores and PANSS score reduction rate between individual and experience groups after treatment(P<0.001),which were lower in individual group than in experience group.The differences in CGI-SI and CGI-GI scores were statistically significant between individual and experience groups after treatment(P<0.05),and CGI-SI and CGI-GI scores were lower in individual group than in experience group.Except for PRL,there were no significant differences in the indexes for glucose metabolism and lipid metabolism between individual and experience groups after treatment(P>0.05).PRL level was lower in individual group than that in experience group(P<0.05).After treatment,the average scores of PSP and GAF in individual group were higher than those in experience group(P<0.001).Conclusion PGx-guided personalized treatment may effectively improve the therapeutic efficacy of antipsychotic drug treatment in patients with schizophrenia,reduce the occurrence of hyperprolactinemia and improve social function of the patients.