From the Department of Neuropsychiatry, Okayama Psychiatric Medical Center, Okayama.
Department of Neuropsychiatry, Yamanashi Prefectural Kita Hospital, Yamanashi.
J Clin Psychopharmacol. 2022;42(2):163-168. doi: 10.1097/JCP.0000000000001492.
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.
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.
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.
Our findings tentatively support the feasibility and clinical utility of once-daily dosing of clozapine in clinical practice. Further studies are needed to replicate these findings and determine causality between dosing strategies and clinical outcomes.
氯氮平的血浆半衰期较短，通常建议采用分剂量给药方案。然而，目前几乎没有证据支持氯氮平的分剂量给药优于每日一次给药。据我们所知，还没有研究检查氯氮平两种给药方案的实际血浆浓度或不良反应之间的差异。我们旨在比较每日一次和分剂量给药方案之间氯氮平的实际血浆浓度，并检查这些方案与氯氮平的精神症状和不良反应之间的关系。
我们分析了日本 2 家医院进行的先前研究的 108 名参与者的数据。使用群体药代动力学模型根据实际血浆浓度估算氯氮平的峰和谷血浆浓度。我们使用Brief Evaluation of Psychosis Symptom Domains 评估精神症状，使用 Glasgow Antipsychotic Side-effects Scale for Clozapine 评估氯氮平的不良反应。
每日一次和分剂量给药方案之间氯氮平的估计峰和谷血浆浓度没有显著差异。除了抑郁/焦虑或氯氮平的主观不良反应外，两种给药策略之间的精神症状没有显著差异。
我们的发现初步支持氯氮平在临床实践中每日一次给药的可行性和临床实用性。需要进一步的研究来复制这些发现，并确定给药策略与临床结果之间的因果关系。
