High Burden of Ileus and Pneumonia in Clozapine-Treated Individuals With Schizophrenia: A Finnish 25-Year Follow-Up Register Study.

IF 15.1 1区 医学 Q1 PSYCHIATRY American Journal of Psychiatry Pub Date : 2024-09-12 DOI:10.1176/appi.ajp.20230744
Juulia J Partanen,Paavo Häppölä,Anders Kämpe,Ari Ahola-Olli,Anni Hellsten,Susanna M Rask,Willehard Haaki,Jarmo Hietala,Olli Kampman,Jari Tiihonen,Antti J Tanskanen,,,Mark J Daly,Samuli Ripatti,Aarno Palotie,Heidi Taipale,Markku Lähteenvuo,Jukka T Koskela
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Abstract

OBJECTIVE The authors used longitudinal biobank data with up to 25 years of follow-up on over 2,600 clozapine users to derive reliable estimates of the real-world burden of clozapine adverse drug events (ADEs). METHODS A total of 2,659 participants in the FinnGen biobank project had a schizophrenia diagnosis and clozapine purchases with longitudinal electronic health record follow-up for up to 25 years after clozapine initiation. Diseases and health-related events enriched during clozapine use were identified, adjusting for disease severity. The incidence and recurrence of ADEs over years of clozapine use, their effect on clozapine discontinuation and deaths, and their pharmacogenetics were studied. RESULTS Median follow-up time after clozapine initiation was 12.7 years. Across 2,157 diseases and health-related events, 27 were enriched during clozapine use, falling into five disease categories: gastrointestinal hypomotility, seizures, pneumonia, other acute respiratory tract infections, and tachycardia, along with a heterogeneous group including neutropenia and type 2 diabetes, among others. Cumulative incidence estimates for ileus (severe gastrointestinal hypomotility) and pneumonia were 5.3% and 29.5%, respectively, 20 years after clozapine initiation. Both events were significantly associated with increased mortality among clozapine users (ileus: odds ratio=4.5; pneumonia: odds ratio=2.8). Decreased genotype-predicted CYP2C19 and CYP1A2 activities were associated with higher pneumonia risk. CONCLUSIONS Clozapine-induced ileus and pneumonia were notably more frequent than has previously been reported and were associated with increased mortality. Two CYP genes influenced pneumonia risk. Pneumonia and ileus call for improved utilization of available preventive measures.
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接受氯氮平治疗的精神分裂症患者肠梗阻和肺炎发病率高:芬兰 25 年随访登记研究》。
目的作者利用对2600多名氯氮平使用者长达25年的纵向生物库数据,得出了氯氮平药物不良事件(ADEs)实际负担的可靠估计值。方法FinnGen生物库项目中共有2659名参与者被诊断为精神分裂症并购买了氯氮平,他们在开始服用氯氮平后接受了长达25年的纵向电子健康记录随访。在对疾病严重程度进行调整后,确定了使用氯氮平期间富集的疾病和健康相关事件。研究了使用氯氮平数年后 ADE 的发生率和复发率、其对氯氮平停药和死亡的影响及其药物遗传学。在 2,157 例疾病和健康相关事件中,有 27 例是在使用氯氮平期间发生的,分为五类疾病:胃肠道功能减退、癫痫发作、肺炎、其他急性呼吸道感染和心动过速,以及包括中性粒细胞减少症和 2 型糖尿病等在内的异质性疾病。开始服用氯氮平 20 年后,回肠梗阻(严重胃肠道功能减退)和肺炎的累积发病率估计分别为 5.3% 和 29.5%。这两种事件与氯氮平使用者死亡率的增加有明显关联(回肠炎:几率比=4.5;肺炎:几率比=2.8)。CYP2C19和CYP1A2基因型预测活性降低与肺炎风险升高有关。两个 CYP 基因影响肺炎风险。肺炎和回肠炎需要更好地利用现有的预防措施。
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来源期刊
American Journal of Psychiatry
American Journal of Psychiatry 医学-精神病学
CiteScore
22.30
自引率
2.80%
发文量
157
审稿时长
4-8 weeks
期刊介绍: The American Journal of Psychiatry, dedicated to keeping psychiatry vibrant and relevant, publishes the latest advances in the diagnosis and treatment of mental illness. The journal covers the full spectrum of issues related to mental health diagnoses and treatment, presenting original articles on new developments in diagnosis, treatment, neuroscience, and patient populations.
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