Impact of patient-specific factors on clozapine metabolism in individuals with treatment-resistant schizophrenia or schizoaffective disorder

作者：Reza Rafizadeh, Anmol Sooch, Alessia Risi, Nicoline Bihelek, Kyler Kanegawa, Alasdair M. Barr, Randall F. White, Christian G. Schütz, Chad Bousman · 发表于：Journal of Psychopharmacology · 年份：2024 · DOI：10.1177/02698811241241394 · 被引用次数：14 · 研究领域：Schizophrenia research and treatment、Tryptophan and brain disorders、Bipolar Disorder and Treatment

Background: There is high inter-individual variability in clozapine metabolism due to genetic and non-genetic differences. Patient-specific factors such as smoking, inflammation indicated by elevated C-reactive protein (CRP), and certain concurrent medications have a significant influence on clozapine metabolism. Aim: To assess which patient-specific factors best explain variability in clozapine metabolism estimated by clozapine concentration to dose (C/D) ratios. Methods: A retrospective cohort analysis using electronic medical data was conducted on 172 inpatients at the BC Psychosis Program. Patients with normal renal and liver function were included if they were on clozapine and had at least one steady-state plasma concentration. The degree of influence of each factor on the variability of clozapine metabolism in the entire cohort and subgroups stratified by fluvoxamine use was evaluated using multiple linear regression analysis of C/D ratios. Results: Model fit testing showed that the entire cohort model accounts for 52.7% of C/D ratio variability, while the no fluvoxamine and fluvoxamine models accounted for 40.8% and 43.8%. In the entire cohort ( n = 172), fluvoxamine use explained the highest variance, and C/D ratios were higher by 30.6% on average. The second strongest predictor was elevated CRP > 10 mg/L, and C/D ratios were higher by 22.9% on average. Subsequently, obesity, nonsmoker status, and female sex explained a significant but modest proportion of variance...