BRIEF RESEARCH REPORT article

Front. Psychiatry

Sec. Psychopharmacology

Volume 16 - 2025 | doi: 10.3389/fpsyt.2025.1591568

Higher clozapine concentration-to-dose ratios at week 1 after initiation are associated with increased risk of clozapine-associated fever in Japanese patients with schizophrenia

Provisionally accepted
Yuki KikuchiYuki Kikuchi1*Hiroaki TanifujiHiroaki Tanifuji2Mutsumi SakataMutsumi Sakata3Kazuro IkawaKazuro Ikawa4Daisuke KumeDaisuke Kume3Naoki HorikawaNaoki Horikawa3Sota UenoSota Ueno2Yoshifumi OnumaYoshifumi Onuma2Masato IshiharaMasato Ishihara2Bunichiro OnoderaBunichiro Onodera2Takeshi ToraiwaTakeshi Toraiwa2Hiroshi KomatsuHiroshi Komatsu5TOSHIHIRO SATOTOSHIHIRO SATO5Masamitsu MaekawaMasamitsu Maekawa5Nariyasu ManoNariyasu Mano5Hiroaki TomitaHiroaki Tomita1
  • 1Department of Psychiatry, Graduate School of Medicine, Tohoku University, Sendai, Japan
  • 2Kodama Hospital, Ishinomaki, Miyagi, Japan
  • 3Nozoe Hills Hospital, Fukuoka, Japan
  • 4Hiroshima University, Hiroshima, Hiroshima, Japan
  • 5Tohoku University Hospital, Sendai, Japan

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The clinical use of clozapine in the treatment of schizophrenia is sometimes halted due to its inflammatory side effects. However, no method has been established for preemptively identifying patients who are at high risk for these events. Therefore, in this study, we assessed whether the blood clozapine concentration-to-dose ratio (C/D) on day 8 after initiation could predict the risk of clozapine-associated fever.Patients whose blood levels of clozapine were measured on day 8 after initiation were retrospectively investigated. The C/D ratio on day 8 was compared between patients who had fever after day 8 and those who did not.Results: A total of 43 patients were included in the study. The range of C/D ratios on day 8 was from 0.35-4.0, with a median of 1.65. Patients with fever had significantly higher C/D ratios on day 8 than those without fever (2.33 vs. 1.47; P < 0.005). Measuring blood clozapine levels on day 8 may help to better estimate the risk of clozapine-associated fever in patients with schizophrenia.

Keywords: adverse effect, C-Reactive Protein, Inflammation, Pneumonia, Myocarditis

Received: 12 Mar 2025; Accepted: 19 May 2025.

Copyright: © 2025 Kikuchi, Tanifuji, Sakata, Ikawa, Kume, Horikawa, Ueno, Onuma, Ishihara, Onodera, Toraiwa, Komatsu, SATO, Maekawa, Mano and Tomita. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Yuki Kikuchi, Department of Psychiatry, Graduate School of Medicine, Tohoku University, Sendai, Japan

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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