Nomogram predicts subtherapeutic clozapine plasma concentrations

A clinical risk score nomogram has demonstrated its utility at predicting the risk level associated with subtherapeutic clozapine plasma concentrations in a recent study.

“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,” the researchers said.

In the study, independent risk factors associated with subtherapeutic clozapine concentrations were identified through univariate and multivariate logistic regression analyses. The research team used these factors to develop a nomogram prediction model.

In multivariate analysis, daily dose (odds ratio [OR], 0.987, 95 percent confidence interval [CI], 0.984‒0.990; p<0.001) and sex (OR, 3.863, 95 percent CI, 2.597‒5.746; p<0.001) independently correlated with subtherapeutic concentrations of clozapine. A predictive nomogram based on this analysis showed good accuracy and discriminative ability, with an area under the curve of 0.760.

Validation of the calibration curve of this model demonstrated a concordance index of 0.764. A decision curve analysis also revealed a greater net benefit value, ranging from 10 percent to 62 percent, with the nomogram predicting the risk of subtherapeutic plasma clozapine concentrations.

“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 researchers said.