Weekly Changes in the Clozapine Concentration-to-Dose Ratio During Clozapine Titration in Japanese Patients With Schizophrenia

BACKGROUND: To prevent inflammatory side effects early in the titration phase of clozapine, international guidelines recommend measuring clozapine blood levels weekly. However, data on such measurements are lacking. METHODS: We retrospectively reviewed the medical records of all patients with schizophrenia who were treated with clozapine for the first time and whose clozapine blood levels were measured for at least 2 consecutive weeks from clozapine initiation at our institution from 2020 to 2024. Patients were divided into 2 groups based on whether they had a fever during the first 6 weeks of clozapine treatment. The clozapine concentration-to-dose (C/D) ratios were compared weekly within 6 weeks after starting clozapine. RESULTS: A total of 28 patients were included in the study, of whom 6 developed a fever and 22 did not. The median C/D ratios in weeks 1 and 2 were significantly higher in patients with a fever than in those without (week 1: 2.12 vs 1.31, P = 0.0217; week 2: 3.48 vs 1.23, P = 0.01). There was no significant difference in C/D ratios between the groups from week 3 to week 6. During the first 6 weeks of treatment, C/D ratios increased markedly and showed peaks in patients with fever but remained stable in patients without fever. CONCLUSIONS: Measuring clozapine blood levels early in the titration phase helps estimate the metabolic capacity of patients. Furthermore, it is essential to pay attention to inflammation, which may increase clozapine C/D ratios.