Slower clozapine titration is associated with delayed onset of clozapine-induced fever among Japanese patients with schizophrenia

Yuki Kikuchi; Yuji Yada; Yuji Otsuka; Fumiaki Ito; Hiroaki Tanifuji; Hiroshi Komatsu; Hiroaki Tomita

doi:10.1038/s41537-023-00412-6

Slower clozapine titration is associated with delayed onset of clozapine-induced fever among Japanese patients with schizophrenia

Schizophrenia (Heidelb). 2023 Nov 20;9(1):82. doi: 10.1038/s41537-023-00412-6.

Authors

Yuki Kikuchi^{1

2}, Yuji Yada³, Yuji Otsuka⁴, Fumiaki Ito⁵, Hiroaki Tanifuji⁶, Hiroshi Komatsu⁷, Hiroaki Tomita^{8

7}

Affiliations

¹ Department of Psychiatry, Graduate School of Medicine, Tohoku University, Sendai, Miyagi, Japan. ykikuchi@sand.ocn.ne.jp.
² Department of Psychiatry, Kodama Hospital, Ishinomaki, Miyagi, Japan. ykikuchi@sand.ocn.ne.jp.
³ Department of Psychiatry, Okayama Psychiatric Medical Center, Okayama, Japan.
⁴ Department of Psychiatry, Asahi General Hospital, Asahi, Japan.
⁵ National Hospital Organization Hanamaki Hospital, Hanamaki, Japan.
⁶ Department of Pharmacy, Kodama Hospital, Ishinomaki, Miyagi, Japan.
⁷ Department of Psychiatry, Tohoku University Hospital, Sendai, Miyagi, Japan.
⁸ Department of Psychiatry, Graduate School of Medicine, Tohoku University, Sendai, Miyagi, Japan.

Abstract

Clozapine-induced fever marks the beginning of its inflammatory and potentially life-threatening adverse effects, such as myocarditis. We retrospectively analyzed the correlation between clozapine titration rate and fever onset date in 254 Japanese patients, including 55 with treatment-resistant schizophrenia who developed clozapine-induced fever. Pearson's product-moment correlation indicated a significant delay in the fever onset date with slower titration. Most fever onset cases occurred within 4 weeks, even with slow titration. Therefore, clinicians should remain vigilant in monitoring clozapine-induced fever within 4 weeks of clozapine initiation, regardless of the titration rate.