Korean J Schizophr Res.  2023 Oct;26(2):52-60. 10.16946/kjsr.2023.26.2.52.

An International Adult Guideline for Making Clozapine Titration Safer by Using Ancestry-Based Personalized Dosing Titrations, C-Reactive Protein and Serum Clozapine Levels: Korean Translation and Its Clinical Application Cases

• Park JS
• Kang N
• Ahn YM
• Kim YS
• Kim SH

• KMID: 2547422
• DOI: http://doi.org/10.16946/kjsr.2023.26.2.52

Abstract

Objectives
During the initial clozapine titration, it is crucial to monitor for inflammatory reactions to ensure safe and effective administration. Clozapine metabolism varies by ancestry, particularly among Asians, warranting lower dosage. Recently, Dr. De Leon introduced guidelines based on ancestral differences. We aimed to provide a Korean translation, focusing on illustrating the necessity through clinical cases.
Methods
The Korean translation of the guidelines, approved by Dr. De Leon, involved two psychiatrists who reviewed and revised each other’s work. An additional board-certified psychiatrist conducted an independent review. We examined two clinical cases from our institution’s database, where clozapine titration faced challenges due to fever and pneumonia, assessing guideline applicability.
Results
The guidelines recommend a target clozapine dose of 175-300 mg/day for Asians with average metabolism and a slower titration rate compared to other ancestries. In both cases, CRP elevation was detected either before or simultaneously with the onset of fever, with a concentration-to-dose ratio ranging from 3.06 to 6.97.
Conclusion
The initial clozapine titration process should consider metabolic differences by ancestry and monitor for inflammation. Further research is needed to optimize the titration process for Koreans, considering metabolic rates, usage patterns, and side effects.

Keyword

Ancestry; Clozapine; C-reactive protein; Metabolism; Titration; 대사; 인종; 적정; 클로자핀; C반응 단백질(CRP)

Figure

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  Fig. 1. Changes in Clozapine Dosage, C-reactive Protein (CRP) Levels, and Fever in Case 1 Patient. This graph represents the dosage of clozapine administered to the patient and the corresponding levels of C-reactive protein (CRP) from the initial day of hospitalization to the first outpatient visit following discharge. The solid line represents the dosage of clozapine, while the dotted line represents the CRP levels. The gray rectangles indicate the days on which fever with a temperature of 37.5ºC or higher was observed at least once.

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  Fig. 2. Changes in Clozapine Dosage, C-reactive Protein (CRP) Levels, and Fever in Case 2 Patient. This graph represents the dosage of clozapine administered to the patient and the corresponding levels of C-reactive protein (CRP). The solid line represents the dosage of clozapine, while the dotted line represents the CRP levels. The gray rectangles indicate the days on which the patient experienced fever with a temperature of 37.5ºC or higher on one or more occasions. The timeline is divided into three periods: the first hospitalization (A), the period between discharge and the second hospitalization (B), and the second hospitalization (C).

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