クロザピン血漿中濃度350 ng/mL未満を予測するための臨床リスクスコアノモグラムの開発と検証：後向きコホート研究

A plasma clozapine concentration below 350 ng/mL may result in treatment failure; however, a rapid method for predicting whether a patient's plasma concentration meets this threshold is lacking. This study aimed to develop a nomogram to predict the risk of subtherapeutic clozapine concentrations in treated patients.

Univariate and multivariate logistic regression analyses were performed to identify independent risk factors associated with subtherapeutic clozapine concentrations. A predictive nomogram prediction model was then constructed based on these factors. The ethics committee of the Xi'an Mental Health Center approved the study (XAJWKY-2024034).

Multivariate logistic regression analysis identified daily dose (OR = 0.987, 95% CI: 0.984-0.990, P < 0.001) and sex (OR = 3.863, 95% CI: 2.597-5.746, P < 0.001) as independent factors influencing the subtherapeutic concentrations of clozapine. A predictive nomogram was constructed based on a multivariable prediction model, which demonstrated good accuracy and discriminative ability, with an area under the curve of 0.760. Validation of the model's calibration curve resulted in a concordance index of 0.764. A decision curve analysis revealed that the nomogram predicting the risk of subtherapeutic plasma clozapine concentrations exhibited a greater net benefit value, ranging from 10% to 62%. Additionally, our research indicated that the daily dosage of clozapine required for male patients to achieve a plasma concentration of 350-600 ng/mL ranges from 228.8 to 392.2 mg, whereas it ranges from 154.2 to 264.3 mg for female patients.

The constructed nomogram was effective at predicting the risk level associated with subtherapeutic clozapine plasma concentrations.