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

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.

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.

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.

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.