Clozapine Once-Versus Multiple-Daily Dosing Regimen: A Single-Center, Retrospective, Cross-Sectional Study

IF 1.7 4区医学 Q3 CLINICAL NEUROLOGY

Human Psychopharmacology: Clinical and Experimental Pub Date : 2025-05-21 DOI:10.1002/hup.70006

Jing Ding, Suo Zhang, Huan Xing, Luyao Li

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引用次数: 0

Abstract

Background

Due to its short plasma half-life, clozapine is typically prescribed in a divided dosing regimen. Although once-daily dosing has proven effective in countries such as Japan, South Korea, Canada, and the United States, its adoption in real-world clinical practice in China remains unclear. This study aimed to compare patient characteristics, psychiatric symptoms, side effects, and plasma clozapine concentrations between once-daily and divided dosing regimens, and to determine the dosage required to achieve plasma levels of 350–600 ng/mL in the Chinese population.

Methods

We conducted a single-center, retrospective, cross-sectional study at Xi'an Mental Health Center, China, collecting data on clozapine-treated patients from March 2019 to March 2021.

Results

Most patients (80% of 198) in the Chinese cohort followed a divided-dose regimen in clinical practice. In the once-daily dosing group, the average plasma clozapine concentration was 158.75 ng/mL, with only 8% of patients reaching the therapeutic window. Conversely, patients on a divided dosing regimen had significantly higher plasma concentrations, averaging 373.34 ng/mL, with 28% within the therapeutic window. The psychiatric symptom remission rate did not differ significantly between the once-daily and divided-dosing groups (50.05% vs. 52.72%, p = 0.718); however, the divided-dosing group experienced a greater variety of adverse effects. Receiver operating characteristic analysis indicated that patients on multiple daily doses require a total daily clozapine dose of 150–250 mg to achieve the target plasma concentration, corresponding to a clozapine concentration-to-dose ratio of 1.4–2.4.

Conclusions

Chinese clinicians generally adhere to a divided dosing schedule for clozapine when the daily dose exceeds 50 mg. Further prospective longitudinal studies are warranted to evaluate whether once-daily dosing regimens can improve clinical outcomes.

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氯氮平一次与多次每日给药方案：单中心、回顾性、横断面研究

由于氯氮平的血浆半衰期短，通常采用分次给药方案。尽管每日一次的剂量在日本、韩国、加拿大和美国等国家已被证明是有效的，但在中国的实际临床实践中，其采用情况仍不清楚。本研究旨在比较每日一次和分次给药方案之间的患者特征、精神症状、副作用和血浆氯氮平浓度，并确定在中国人群中达到350-600 ng/mL血浆水平所需的剂量。方法我们在中国西安精神卫生中心进行了一项单中心、回顾性、横断面研究，收集了2019年3月至2021年3月氯氮平治疗患者的数据。结果在临床实践中，中国队列中大多数患者（198例中的80%）采用分次给药方案。在每日一次给药组中，氯氮平平均血浆浓度为158.75 ng/mL，只有8%的患者达到治疗窗口期。相反，采用分次给药方案的患者血浆浓度明显较高，平均为373.34 ng/mL，其中28%在治疗窗内。每日一次给药组和分次给药组的精神症状缓解率无显著差异（50.05% vs 52.72%, p = 0.718）；然而，分组给药组出现了更多的不良反应。受试者工作特征分析表明，每日多次给药的患者需要每日氯氮平总剂量150 ~ 250mg才能达到目标血药浓度，对应的氯氮平浓度剂量比为1.4 ~ 2.4。结论当氯氮平日剂量超过50mg时，我国临床医生普遍采用分次给药方案。需要进一步的前瞻性纵向研究来评估每日一次给药方案是否能改善临床结果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Human Psychopharmacology: Clinical and Experimental 医学-精神病学

CiteScore

4.10

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Human Psychopharmacology: Clinical and Experimental provides a forum for the evaluation of clinical and experimental research on both new and established psychotropic medicines. Experimental studies of other centrally active drugs, including herbal products, in clinical, social and psychological contexts, as well as clinical/scientific papers on drugs of abuse and drug dependency will also be considered. While the primary purpose of the Journal is to publish the results of clinical research, the results of animal studies relevant to human psychopharmacology are welcome. The following topics are of special interest to the editors and readers of the Journal: -All aspects of clinical psychopharmacology- Efficacy and safety studies of novel and standard psychotropic drugs- Studies of the adverse effects of psychotropic drugs- Effects of psychotropic drugs on normal physiological processes- Geriatric and paediatric psychopharmacology- Ethical and psychosocial aspects of drug use and misuse- Psychopharmacological aspects of sleep and chronobiology- Neuroimaging and psychoactive drugs- Phytopharmacology and psychoactive substances- Drug treatment of neurological disorders- Mechanisms of action of psychotropic drugs- Ethnopsychopharmacology- Pharmacogenetic aspects of mental illness and drug response- Psychometrics: psychopharmacological methods and experimental design