Clinical Cognitive Neuroscience Center

Publication

International

Association between initial pattern of clozapine titration, concentration-to-dose ratio, and incidence of fever in patients with schizophrenia spectrum disorders in a Korean tertiary hospital
Journal
Schizophrenia Research
Author
Nuree Kang, Se Hyun Kim, Jayoun Kim, Sungkyu Kim, Jinhyeok Jang, Heesoo Yoon, Junhee Lee, Minah Kim, Yong Sik Kim, Jun Soo Kwon
Year
2023
Date
08/24

Safe and effective administration of clozapine requires careful monitoring for inflammatory reactions during the initial titration. The concentration-to-dose (C/D) ratio must be taken into account, which may vary among ethnicities. In this retrospective study, 1408 Korean schizophrenia inpatients were examined for during the first 8 weeks of clozapine titration. The average doses of clozapine administered during weeks 1, 2, 4, and 8 were 77.37, 137.73, 193.20, and 212.83 mg/day, with significantly lower doses for females than males. The average C/D ratio was significantly higher in females (1.75 ± 1.04 and 1.11 ± 0.67 ng/mL per mg/day). Patients with higher C/D ratios were more likely to experience fever and were prescribed lower doses of clozapine starting from week 4. In total, 22.1 % of patients developed a fever at an average of 15.74 days after initiating clozapine. Patients who developed a fever were younger, used more antipsychotics at baseline, had a higher C/D ratio, and had a higher incidence of an elevated C-reactive protein level. A higher C/D ratio, use of a greater number of antipsychotics at baseline, and concomitant olanzapine use were risk factors for the development of inflammatory reactions. The incidence of pneumonia, agranulocytosis, and myocarditis within 8 weeks were 3.7 %, 0.3 %, and 0.1 %. In summary, the target dose of clozapine titration is lower for Korean schizophrenia patients, with a higher C/D ratio and more frequent fever compared to Western patients; however, myocarditis occurs rarely. Our findings may contribute to the titration methods for clozapine for the East Asian population.

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