Data Management and Analysis Centre, Discipline of Public Health, University of Adelaide, Adelaide, South Australia, Australia.
Drugs Aging. 2010 Nov 1;27(11):885-93. doi: 10.2165/11584490-000000000-00000.
Antipsychotics are commonly used in the elderly despite a lack of safety data from randomized trials, particularly for the typical antipsychotics. Observational studies have investigated the association between antipsychotics and stroke but results vary, which may be due to lack of control for unmeasured confounding.
To estimate the risk of hospitalization for stroke in elderly users of antipsychotics.
Using the Australian Government Department of Veterans' Affairs administrative claims dataset we utilized a self-controlled case series design to risk-adjust for potential unmeasured confounding. Risk periods prior to antipsychotic initiation were also included to search for evidence of confounding by indication. Unexposed patients were included to adjust for the increasing incidence of hospitalization for stroke with age.
There were 10 638 patients aged ≥65 years with at least one hospitalization for stroke identified during the 4-year period from 1 January 2003 to 31 December 2006. Of these, 514 patients were initiated on typical antipsychotics and 564 patients were initiated on atypical antipsychotics. Hospitalization for stroke was increased in the first week after initiation of a typical antipsychotic (incidence rate ratio [IRR] 2.3; 95% CI 1.3, 3.8). There was no evidence of an increased risk of hospitalization for stroke after initiation of atypical antipsychotics. The risk of hospitalization for stroke progressively increased in the weeks leading up to first-time antipsychotic treatment. However, while the risk of hospitalization for stroke in the week prior to initiating antipsychotic therapy was significantly increased for patients initiated on typical antipsychotics (IRR 7.2; 95% CI 5.3, 9.8), patients initiated on atypical antipsychotics had no excess risk in the same period (IRR 1.2; 95% CI 0.7, 2.3).
The results of this study are consistent with randomized controlled trial evidence indicating that there is no increased risk of serious cerebrovascular events requiring hospitalization in patients taking atypical antipsychotics. No randomized controlled trial evidence is available on the risk of hospitalization for stroke with use of typical antipsychotics in the elderly. This study found a small but significantly increased risk of hospitalization for stroke immediately following the initiation of typical antipsychotics. Antipsychotics are likely to be initiated after hospitalization for stroke. This practice is likely to reflect the prescribing of antipsychotics during hospital admission for post-stroke complications such as delirium; however, the long-term effects of this practice are unknown.
尽管随机试验缺乏安全性数据，但抗精神病药仍在老年人中广泛应用，尤其是典型抗精神病药。观察性研究已经调查了抗精神病药与中风之间的关联，但结果各不相同，这可能是由于缺乏对未测量混杂因素的控制。
评估老年抗精神病药使用者因中风住院的风险。
我们利用澳大利亚退伍事务部行政索赔数据集，采用自我对照病例系列设计，对潜在未测量的混杂因素进行风险调整。还包括抗精神病药起始前的风险期，以寻找指示性混杂的证据。纳入未暴露的患者是为了调整随着年龄增长中风住院率的增加。
在 2003 年 1 月 1 日至 2006 年 12 月 31 日的 4 年期间，共发现 10638 名年龄≥65 岁且至少有一次中风住院的患者。其中，514 名患者开始使用典型抗精神病药，564 名患者开始使用非典型抗精神病药。在开始使用典型抗精神病药的第一周，中风住院的风险增加（发病率比 [IRR] 2.3；95%置信区间 [CI] 1.3，3.8）。没有证据表明使用非典型抗精神病药后中风住院的风险增加。在首次使用抗精神病药前的几周内，中风住院的风险逐渐增加。然而，虽然开始使用典型抗精神病药的患者在开始抗精神病治疗前一周的中风住院风险显著增加（IRR 7.2；95%CI 5.3，9.8），但同期开始使用非典型抗精神病药的患者风险没有增加（IRR 1.2；95%CI 0.7，2.3）。
本研究结果与随机对照试验证据一致，表明服用非典型抗精神病药的患者无严重脑血管事件导致需要住院治疗的风险增加。没有随机对照试验证据表明在老年人中使用典型抗精神病药与中风住院风险相关。本研究发现，在开始使用典型抗精神病药后，中风住院的风险略有但显著增加。抗精神病药很可能在中风后住院时开始使用。这种做法可能反映了在因中风后并发症（如谵妄）住院期间开具抗精神病药的情况；然而，这种做法的长期影响尚不清楚。
