{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T15:48:42Z","timestamp":1792684122362,"version":"4.5.0"},"reference-count":34,"publisher":"Royal College of Psychiatrists","issue":"5","license":[{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Br J Psychiatry"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:sec id=\"S0007125024001132_sec_a1\"><jats:title>Background<\/jats:title><jats:p>Clozapine-induced inflammation, such as myocarditis and pneumonia, can occur during initial titration and can be fatal. Fever is often the first sign of severe inflammation, and early detection and prevention are essential. Few studies have investigated the effects of clozapine titration speed and concomitant medication use on the risk of clozapine-induced inflammation.<\/jats:p><\/jats:sec><jats:sec id=\"S0007125024001132_sec_a2\"><jats:title>Aims<\/jats:title><jats:p>We evaluated the risk factors for clozapine-associated fever, including titration speed, concomitant medication use, gender and obesity, and their impact on the risk of fever and the fever onset date.<\/jats:p><\/jats:sec><jats:sec id=\"S0007125024001132_sec_a3\" sec-type=\"methods\"><jats:title>Method<\/jats:title><jats:p>We conducted a case-control study. The medical records of 539 Japanese participants with treatment-resistant schizophrenia at 21 hospitals in Japan who received clozapine for the first time between 2010 and 2022 were retrospectively investigated. Of these, 512 individuals were included in the analysis. Individuals were divided into three groups according to the titration rate recommended by international guidelines for East Asians: the faster titration group, the slower titration group and the ultra-slower titration group. The use of concomitant medications (such as antipsychotics, mood stabilisers, hypnotics and anxiolytics) at clozapine initiation was comprehensively investigated. Logistic regression analysis was performed to identify the explanatory variables for the risk of a fever of 37.5\u00b0C or higher lasting at least 2 days.<\/jats:p><\/jats:sec><jats:sec id=\"S0007125024001132_sec_a4\" sec-type=\"results\"><jats:title>Results<\/jats:title><jats:p>Fever risk significantly increased with faster titration, male gender and concomitant use of valproic acid or quetiapine. No increased fever risk was detected with the use of other concomitant drugs, such as olanzapine, lithium or orexin receptor antagonists. Fever onset occurred significantly earlier with faster titration. Multivariate analysis identified obesity as being a factor that accelerated fever onset.<\/jats:p><\/jats:sec><jats:sec id=\"S0007125024001132_sec_a5\" sec-type=\"conclusions\"><jats:title>Conclusion<\/jats:title><jats:p>A faster titration speed and concomitant treatment with valproic acid and quetiapine at clozapine initiation increased the risk of clozapine-associated fever. Clinicians should titrate clozapine with caution and consider both the titration speed and concomitant medications.<\/jats:p><\/jats:sec>","DOI":"10.1192\/bjp.2024.113","type":"journal-article","created":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T04:10:13Z","timestamp":1722917413000},"page":"492-498","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":16,"title":["Effects of titration speed, gender, obesity and concomitant medications on the risk and onset time of clozapine-associated fever among Japanese patients with schizophrenia: retrospective review of charts from 21 hospitals"],"prefix":"10.1192","volume":"225","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1184-8918","authenticated-orcid":false,"given":"Yuki","family":"Kikuchi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Kurosawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mutsumi","family":"Sakata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyohei","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Tomita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Yoshio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4414-3770","authenticated-orcid":false,"given":"Norio","family":"Yasui-Furukori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"170","published-online":{"date-parts":[[2024,8,6]]},"reference":[{"key":"S0007125024001132_ref1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2023.0376"},{"key":"S0007125024001132_ref7","first-page":"e70","article-title":"Japanese patients need slower, personalized clozapine titrations: a comment on the case described by Kikuchi et al","volume":"2","author":"Yasui-Furukori","year":"2023","journal-title":"Psychiatry Clin Neurosci Rep"},{"key":"S0007125024001132_ref6","doi-asserted-by":"publisher","DOI":"10.1136\/gpsych-2022-100773"},{"key":"S0007125024001132_ref29","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyac036"},{"key":"S0007125024001132_ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2019.07.040"},{"key":"S0007125024001132_ref24","doi-asserted-by":"publisher","DOI":"10.1111\/pcn.12275"},{"key":"S0007125024001132_ref28","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000001177"},{"key":"S0007125024001132_ref18","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2023.115336"},{"key":"S0007125024001132_ref19","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2022.2160318"},{"key":"S0007125024001132_ref31","first-page":"e113","article-title":"Hypnotic prescriptions in 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Published by Cambridge University Press on behalf of Royal College of Psychiatrists","name":"copyright","label":"Copyright","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}}]}}