Current practice for clozapine-induced leukopenia in Japanese psychiatric hospitals: A nationwide survey

Tomihisa Niitsu; Norio Yasui-Furukori; Ken Inada; Tetsufumi Kanazawa; Masaomi Iyo; Takefumi Ueno; Ryota Hashimoto

doi:10.1016/j.schres.2023.10.011

Current practice for clozapine-induced leukopenia in Japanese psychiatric hospitals: A nationwide survey

Schizophr Res. 2023 Oct 27:S0920-9964(23)00372-9. doi: 10.1016/j.schres.2023.10.011. Online ahead of print.

Authors

Tomihisa Niitsu¹, Norio Yasui-Furukori², Ken Inada³, Tetsufumi Kanazawa⁴, Masaomi Iyo⁵, Takefumi Ueno⁶, Ryota Hashimoto⁷

Affiliations

¹ Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan. Electronic address: niitsu@chiba-u.jp.
² Department of Psychiatry, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan.
³ Department of Psychiatry, Kitasato University School of Medicine, Kanagawa, Japan.
⁴ Department of Neuropsychiatry, Osaka Medical and Pharmaceutical University, Osaka, Japan.
⁵ Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan.
⁶ National Hospital Organization, Hizen Psychiatric Medical Center, Saga, Japan.
⁷ Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan.

PMID: 38038428
DOI: 10.1016/j.schres.2023.10.011

Abstract

Clozapine is an atypical antipsychotic used for treatment-resistant schizophrenia. In Japan, its use requires management by a blood monitoring system called the Clozaril Patient Monitoring Service (CPMS) for the early detection of serious side effects such as agranulocytosis, which is extremely rare. Monitoring services vary among the clozapine suppliers in different countries. Additionally, Japanese patients can be started on clozapine treatment exclusively through an 18-week inpatient admission at a psychiatric hospital capable of coordinating with a hematologist. One reported reason for the lack of widespread clozapine use in Japan is the difficulty in establishing collaboration with hematologists when agranulocytosis/leukopenia occurs. Hence, we conducted a nationwide web-based survey of CPMS-registered psychiatric facilities in Japan to determine the status of collaboration with hematology departments. Valid responses were received from the psychiatrists responsible for prescribing clozapine at 203 of the 547 facilities (response rate: 37.1 %). The largest number of psychiatric facilities (61 %) collaborated with hematologists at another facility with a psychiatry department, while psychiatrists in 32 % of the facilities worked with hematologists at their own facilities. Most patients with clozapine-induced agranulocytosis/leukopenia could be treated with clozapine discontinuation and follow-up in psychiatric inpatient units with the assistance of a hematologist. The actual workload of hematologists was limited, and the patients might experience the burden of repeated blood sampling. This study suggests that disseminating information regarding the status of collaborations with hematologists may promote the widespread use of clozapine in Japan. SHORT COMMENT FOR TWITTER: This study suggests that most patients with clozapine-induced agranulocytosis/leukopenia could be treated with clozapine discontinuation and follow-up in psychiatric inpatient units with the assistance of a hematologist.

Keywords: Agranulocytosis; Clozapine; Hematology; Neutropenia; Schizophrenia; Severe adverse event.