The Effect of Clozapine on Premature Mortality: An Assessment of Clinical Monitoring and Other Potential Confounders
The Effect of Clozapine on Premature Mortality: An Assessment of Clinical Monitoring and Other Potential Confounders
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DOI：
10.1093/schbul/sbu120
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发表时间：
2015-05-01
影响因子：
6.6
通讯作者：
Stewart, Robert
中科院分区：
文献类型：
--
作者：
Hayes, Richard D.;Downs, Johnny;Stewart, Robert
氯氮平可引起严重的不良反应，但它与降低死亡风险有关。我们检验了这种关联是由于临床监测增加所致的假设，并调查了自然原因过早死亡的风险。我们在与全国死亡率追踪相关的大型专业精神保健病例登记册中确定了 14 754 名患有严重精神疾病 (SMI) 的人（879 人死亡），其中包括年龄≥ 15 岁的精神分裂症、分裂情感和双相情感障碍。在这项队列研究中，我们使用 Cox 回归模拟了 5 年期间（2007-2011 年）氯氮平对死亡率的影响。服用氯氮平的个体有更严重的精神病理学和更差的功能状态。许多与氯氮平使用相关的暴露本身就是死亡率增加的危险因素。然而，我们发现服用氯氮平与降低死亡率之间存在很强的相关性，在控制了广泛的潜在混杂因素（包括临床监测和疾病严重程度标志物）后，这种相关性仍然存在（调整后的危险比 0.4；95% CI 0.2-0.7；p = 0.001）。在将样本限制为诊断为精神分裂症或服用抗精神病药物的患者以及使用倾向评分来减少适应症混杂的影响后，这种关联仍然存在。在 SMI 患者中，服用氯氮平的患者因自然和非自然原因死亡的风险降低。我们没有发现任何证据表明 SMI 中氯氮平死亡率降低是由于临床监测的增加或混杂因素所致。这是第一项报告氯氮平与降低自然原因死亡风险之间关联的研究。
Clozapine can cause severe adverse effects yet it is associated with reduced mortality risk. We test the hypothesis this association is due to increased clinical monitoring and investigate risk of premature mortality from natural causes. We identified 14 754 individuals (879 deaths) with serious mental illness (SMI) including schizophrenia, schizoaffective and bipolar disorders aged >= 15 years in a large specialist mental healthcare case register linked to national mortality tracing. In this cohort study we modeled the effect of clozapine on mortality over a 5-year period (2007-2011) using Cox regression. Individuals prescribed clozapine had more severe psychopathology and poorer functional status. Many of the exposures associated with clozapine use were themselves risk factors for increased mortality. However, we identified a strong association between being prescribed clozapine and lower mortality which persisted after controlling for a broad range of potential confounders including clinical monitoring and markers of disease severity (adjusted hazard ratio 0.4; 95% CI 0.2-0.7; p = .001). This association remained after restricting the sample to those with a diagnosis of schizophrenia or those taking antipsychotics and after using propensity scores to reduce the impact of confounding by indication. Among individuals with SMI, those prescribed clozapine had a reduced risk of mortality due to both natural and unnatural causes. We found no evidence to indicate that lower mortality associated with clozapine in SMI was due to increased clinical monitoring or confounding factors. This is the first study to report an association between clozapine and reduced risk of mortality from natural causes.