豫南地区精神分裂症患者氯氮平高血药浓度的影响因素及风险预测模型的构建

目的：分析豫南地区精神分裂症患者发生氯氮平高血药浓度的风险因素，建立氯氮平高血药浓度的风险预测模型。方法：纳入接受氯氮平治疗的631名精神分裂症患者，根据氯氮平血药浓度监测值分为超标组（≥ 600 ng·mL^-1）140例和对照组（<600 ng·mL^-1）491例。采用二元Logistic回归分析筛选出氯氮平高血药浓度的独立危险因素，构建氯氮平高血药浓度的列线图预测模型。结果：性别（OR=4.127，P<0.001）、BMI （OR=1.074，P=0.01）、日剂量（OR=1.013，P<0.001）、发热（OR=19.266，P<0.001）、氯氮平服药史（OR=2.505，P<0.001）、联用美托洛尔（OR=2.446，P=0.007）、联用普萘洛尔（OR=2.493，P=0.003）是发生氯氮平高血药浓度的独立危险因素。构建的列线图AUC达到0.870，校准曲线显示预测概率与实际概率之间具有最佳一致性。结论：性别、BMI、剂量、发热、服药史、联用美托洛尔、联用普萘洛尔是豫南地区精神分裂症患者发生氯氮平高血药浓度的独立危险因素，该研究构建的列线图具有最佳辨别力和出色的校准能力。

Influencing factors of high clozapine plasma concentration in patients with schizophrenia in Southern Henan and construction of risk prediction model

OBJECTIVE To analyze the risk factors of high clozapine plasma concentration in patients with schizophrenia in Southern Henan, and to establish a risk prediction model of high clozapine plasma concentration.METHODS 631 patients with schizophrenia treated with clozapine were included.According to the clozapine plasma concentration monitoring value, they were divided into 140 cases in the over-standard group (≥ 600 ng·mL^-1) and 491 cases in the control group (<600 ng·mL ^-1).Binary logistic regression analysis was used to screen out independent risk factors for high clozapine plasma concentration.Construct a nomogram to predict the risk of high clozapine plasma concentration.RESULTS Gender (OR=4.127, P<0.001), BMI (OR=1.074, P=0.01), daily dose (OR=1.013, P<0.001), fever (OR=19.266, P<0.001), clozapine medication history (OR=2.505, P<0.001), combined with metoprolol (OR=2.446, P=0.007), combined with propranolol (OR=2.493, P=0.003) were independent risk factors for high clozapine plasma concentration.The AUC of nomogram reached 0.870.The calibration curve showed the best consistency between predicted probability and actual probability.CONCLUSION Gender, BMI, daily dose, fever, medication history, combined with metoprolol, and combined with propranolol were independent risk factors that lead to high clozapine plasma concentration in patients with schizophrenia in southern Henan.The nomogram constructed in this study had optimal discrimination and excellent calibration.