Department of Neuropsychiatry, Faculty of Medicine, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan.
Department of Pharmacy, Osaka Medical and Pharmaceutical University Hospital, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan.
J Psychiatr Res. 2021 Sep;141:116-123. doi: 10.1016/j.jpsychires.2021.06.041. Epub 2021 Jun 23.
Clozapine is the only effective antipsychotic drug used for the treatment of treatment-resistant schizophrenia. Although it has been shown that the frequency of clozapine use is very low in Japan, our previous study revealed that the number of clozapine prescriptions has been increasing in recent years, and that risk factors leading to discontinuation of clozapine were also identified as age ≥40 years, poor tolerability to olanzapine, previous treatment with clozapine, and white blood cell count <6000/mm. The main cause for discontinuation of clozapine is the occurrence of a wide range of adverse events, including neutropenia/leukopenia and fatal cardiac disorders. In this study, we analyzed the physical details and backgrounds of patients with adverse events that led to clozapine discontinuation using a national registry database of more than 8000 Japanese patients. The physical adverse events that led to discontinuation of clozapine were neutropenia/leukopenia, glucose intolerance, cardiac disorders, gastrointestinal disorders, neuroleptic malignant syndrome, pleurisy, pulmonary embolism, sedation/somnolence, and seizures. Neutropenia/leukopenia had the highest incidence (5.0%). Neutropenia/leukopenia and cardiac disorders tended to occur early in the treatment period, indicating the need for careful monitoring for these adverse events in the early stages of clozapine treatment. Gastrointestinal disorders occurred over a long period of time, suggesting the need for careful observation during the maintenance period. The data obtained in our study will lead to the optimal and safe use of clozapine treatment.
氯氮平是唯一有效的抗精神病药物，用于治疗治疗抵抗性精神分裂症。虽然已经表明，氯氮平在日本的使用频率非常低，但我们之前的研究表明，近年来氯氮平的处方数量一直在增加，导致氯氮平停药的风险因素也被确定为年龄≥40 岁、对奥氮平的耐受性差、以前使用过氯氮平和白细胞计数<6000/mm。氯氮平停药的主要原因是发生了广泛的不良事件，包括中性粒细胞减少/白细胞减少和致命性心脏疾病。在这项研究中，我们使用了超过 8000 名日本患者的国家注册数据库分析了导致氯氮平停药的不良事件患者的身体细节和背景。导致氯氮平停药的身体不良事件包括中性粒细胞减少/白细胞减少、葡萄糖不耐受、心脏疾病、胃肠道疾病、神经阻滞剂恶性综合征、胸膜炎、肺栓塞、镇静/嗜睡和癫痫发作。中性粒细胞减少/白细胞减少发生率最高（5.0%）。中性粒细胞减少/白细胞减少和心脏疾病在治疗早期倾向于发生，这表明在氯氮平治疗的早期阶段需要仔细监测这些不良事件。胃肠道疾病持续时间较长，这表明在维持期需要仔细观察。我们研究中获得的数据将导致氯氮平治疗的最佳和安全使用。
