clozapine-induced agranulocytosis and glucose intolerance

2022 Fiscal Year Final Research Report

• Project/Area Number: 17K10269
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Niigata University
• Principal Investigator: ONO SHIN 新潟大学, 医歯学総合病院, 講師 (60623402)
• Project Period (FY): 2017-04-01 – 2023-03-31
• Keywords: 統合失調症 / クロザピン

Outline of Final Research Achievements

Clozapine is the only effective drug for treatment-resistant schizophrenia, and while its clinical efficacy is promising, the emergence of serious side effects such as agranulocytosis, granulocytopenia, and glucose intolerance has not made treatment with this drug widespread enough. Therefore, there is an urgent need to improve the safety of CLZ, but the mechanisms of its adverse effects are not well understood and are difficult to predict or avoid. In this study, we aimed to elucidate the mechanisms of CLZ-induced abnormal glucose metabolism and weight gain, and the involvement of delayed immune response in CLZ-induced agranulocytosis and granulocytopenia. In collecting samples, the study was completed without any cases of clozapine-induced agranulocytosis or granulocytopenia.

Free Research Field

臨床精神薬理

Academic Significance and Societal Importance of the Research Achievements

無顆粒球症、顆粒球減少症のサンプルが得られず、メカニズムの解明には至らなかった。好中球数が正常範囲であるクロザピン内服中のサンプルでは、DLST（薬剤によるリンパ球幼若化試験）での陽性判定サンプルはなかった。また、炎症系サイトカインとDLSTの関連は判定できず、各炎症系サイトカインとクロザピン内服用量との有意な関連は認めなかった。クロザピン開始後の血糖について、開始時HbA1cとHbA1c変化量（1年間）は有意な相関を認め（相関係数－0.673　P<0.001：Y=-0.533X＋2.944）、今後遺伝子多型との関連解析を進める予定である。