Clozapine Once-Daily Versus Divided Dosing Regimen

作者：Kohei Kitagawa, Ryuhei So, Nobuyuki Nomura, Masaru Tsukahara, Fuminari Misawa, Masafumi Kodama, Hiroyuki Uchida, Robert R. Bies, Thomas Straubinger, Christopher Banker, Yuya Mizuno, Masaru Mimura, Hiroyoshi Takeuchi · 发表于：Journal of Clinical Psychopharmacology · 年份：2021 · DOI：10.1097/jcp.0000000000001492 · 被引用次数：12 · 研究领域：Schizophrenia research and treatment、Treatment of Major Depression、Bipolar Disorder and Treatment

Abstract Objective Clozapine is generally recommended to be prescribed in a divided dosing regimen based on its relatively short plasma half-life. However, there has been little evidence to support the superiority of divided dosing of clozapine over once-daily dosing. To our knowledge, there have been no studies examining differences in actual plasma concentrations or adverse effects between the 2 dosing strategies of clozapine. We aimed to compare actual plasma concentrations of clozapine between once-daily and divided dosing regimens, and to examine the relationships of these regimens with psychiatric symptoms and adverse effects of clozapine. Methods We analyzed data from 108 participants of a previous study conducted in 2 hospitals in Japan. A population pharmacokinetic model was used to estimate the peak and trough plasma concentrations of clozapine based on actual plasma concentrations. We evaluated psychiatric symptoms with the Brief Evaluation of Psychosis Symptom Domains and adverse effects of clozapine with the Glasgow Antipsychotic Side-effects Scale for Clozapine. Results The estimated peak and trough plasma concentrations of clozapine did not differ significantly between once-daily and divided dosing regimens. There were no significant differences in psychiatric symptoms except for depression/anxiety or subjective adverse effects of clozapine between the 2 dosing strategies. Conclusions Our findings tentatively support the feasibility and clinical utility of once...