2019—2021年2992例次丙戊酸治疗药物监测结果的回顾性分析

Retrospective Analysis of 2992 Times of Therapeutic Drug Monitoring of Valproic Acid from 2019 to 2021

背景丙戊酸作为一种心境稳定剂,广泛用于双相情感障碍及其他精神疾病的治疗。尽管丙戊酸的治疗药物监测(TDM)在国内外已开展多年,但年龄、性别等因素对其血药浓度的影响仍存在一定争议。目的分析丙戊酸TDM结果,为丙戊酸治疗双相情感障碍等精神疾病的个体化、合理化用药提供参考。方法基于瑞美医学实验室Lis信息检索系统,收集西安市精神卫生中心2019—2021年所有进行丙戊酸血药浓度监测的门诊及住院患者的年龄、性别以及TDM原始数据、监测例数、监测频次等。根据《神经精神药理学与药物精神病学协会(AGNP)-神经精神TDM共识指南》推荐的治疗窗浓度参考范围进行分类统计,计算丙戊酸TDM在低于治疗窗(<50 mg/L)、治疗窗内(50~100 mg/L)和高于治疗窗(>100 mg/L)的分布情况。采用Med Calc 5.2医学统计软件进行数据分析。结果2431例患者共计监测2992次,其中男性监测1637次,女性监测1355次。与2019年监测次数相比,2020年及2021年监测次数分别增长54.93%、44.00%。2992例监测样本中,仅接受1次监测的占比约为74.41%;监测频次为1次的门诊患者比例高于住院患者(χ^(2)=95.15,P<0.001);监测频次为2、3次以上的住院患者比例均高于门诊患者(χ^(2)=49.41、34.24,P<0.001)。门诊患者丙戊酸血药浓度低于住院患者(Z=-11.60,P<0.001);男性患者丙戊酸血药浓度低于女性患者(Z=-4.39,P<0.001);不同年龄段患者丙戊酸血药浓度比较,差异无统计学意义(Z=0.75,P>0.05)。2019—2021年丙戊酸TDM在治疗窗内的监测比例为57.72%,高于在低于治疗窗及高于治疗窗的监测比例(χ^(2)=155.38、1216.68,P<0.001)。不同年份、年龄段、性别丙戊酸TDM在低于治疗窗、治疗窗内、高于治疗窗的监测比例比较,差异均有统计学意义(P<0.05)。男性、女性及总体样本丙戊酸血药浓度均为40~80 mg/L,稍低于AGNP共识推荐的丙戊酸“治疗窗浓度参考范围”(50~100 mg/L)。结论在临床实践中,应根据不同性别、年龄进行个体化给药以提高丙戊酸血药浓度在治疗窗的比例,同时应加强门诊及住院患者丙戊酸TDM的重视程度,保障临床用药的安全、有效。

Background Valproic acid,as a mood stabilizer,has been extensively used for the treatment of bipolar disorder and other psychiatric conditions.Although therapeutic drug monitoring(TDM)of valproic acid has been carried out at home and abroad for many years,controversies persist regarding the influence of age,sex and other factors on its plasma concentration.Objective To analyze the TDM results of valproic acid,providing a reference for rationalized individualized treatment of bipolar disorders or other psychiatric conditions.Methods Through the laboratory information system of Ruimei Medical Laboratory,information on TDM of valproic acid in outpatients and inpatients(including the patient's age,sex,TDM raw data,monitoring samples,and monitoring frequency)was obtained from Xi'an Mental Health Center from 2019 to 2021.The plasma concentration of valproic acid was classified into three categories(<50 mg/L,50-100 mg/L and>100 mg/L)according to the therapeutic window range recommended in the Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology(hereinafter referred to as AGNP Consensus),and the percent of each category was calculated.And subsequent data analysis was performed using MedCalc 5.2.Results A total of 2431 patients were monitored 2992 times for understanding valproic acid treatment status,of which 1637 were for men,and 1355 for women.The frequencies of TDM of valproic acid increased by 54.93%in 2020 and 44.00%in 2021 compared to those reported in 2019.The proportion of patients who received only once was about 74.41%.Compared with inpatients,outpatients had higher prevalence of receiving one TDM of valproic acid(χ^(2)=95.15,P<0.001),and lower prevalence of receiving two,or at least three TDM of valproic acid(χ^(2)=49.41,34.24,P<0.001).The plasma valproic acid concentration in inpatients was higher than that in outpatients(Z=-11.60,P<0.001).Meanwhile,higher plasma valproic acid concentration was observed in female patients than in male patients(Z=-4.39,P<0.001).However,there was no significant difference between the age groups(Z=0.75,P>0.05).For each study year 2019-2021,the proportion of plasma concentration of valproic acid within the therapeutic window was 57.72%,which was significantly higher than that of the proportion of below and above the therapeutic window(χ^(2)=155.38,1216.68,P<0.001).The proportion of the plasma valproic acid concentration(<50 mg/L,50-100 mg/L,or>100 mg/L)had statistically significant differences between different age and gender groups,and over the years(P<0.05).The plasma valproic acid concentration ranged between 40-80 mg/L for males,females,or total participants,which was slightly lower than the therapeutic range(50-100 mg/L)recommended by the AGNP Consensus.Conclusion The individual treatment program in patients should be determined clinically according to age and sex to increase the proportion of plasma valproic acid concentration in the therapeutic window.Additionally,TDM of valproic acid should be emphasized in inpatients and outpatients to ensure safe and effective medication administration in clinical practice.