本文由小咖机器人翻译整理

期刊来源：BMJ

原文链接：https://doi.org/10.1136/bmj-2023-076268

摘要内容如下：

客观

调查与痴呆患者使用抗精神病药物相关的多种不良结局的风险。

设计

基于人群的配对队列研究。

设置

来自英国临床实践研究数据链（CPRD）的相关初级保健、医院和死亡率数据。

人口

1998年1月1日至2018年5月31日期间诊断为痴呆的成人（≥50岁）（n=173910，63.0%为女性）。每个新的抗精神病药物使用者（n=35339，62.5%为女性）与最多15个非使用者匹配，使用发病率密度抽样。

主要结果指标

主要转归为卒中、静脉血栓栓塞、心肌梗死、心力衰竭、室性心律失常、骨折、肺炎和急性肾损伤，按抗精神病药物使用时间分层，绝对风险使用抗精神病药物使用者与匹配对照的累积发生率计算。还研究了阑尾炎和胆囊炎合并的无关（阴性对照）结果，以检测潜在的未测量的混杂因素。

结果

与未使用抗精神病药物相比，除室性心律失常外，任何抗精神病药物的使用均与所有结局的风险增加相关。当前使用（处方后90天）与肺炎（危害比2.19，95%可信区间（CI）2.10至2.28）、急性肾损伤（1.72，1.61至1.84）、静脉血栓栓塞（1.62，1.46至1.80）、中风（1.61，1.52至1.71）、骨折（1.43，1.35至1.52）、心肌梗死（1.28，1.15至1.42）、心力衰竭（1.27，1.18至1.37）。未观察到阴性对照结果（阑尾炎和胆囊炎）的风险增加。在开始用药后90天内，抗精神病药物使用者肺炎的累积发生率为4.48%（4.26%-4.71%），而匹配的非使用者队列为1.49%（1.45%-1.53%）（差异2.99%，95%CI 2.77%-3.22%）。

结论

在成年痴呆患者中，与未使用抗精神病药物相比，使用抗精神病药物与卒中、静脉血栓栓塞、心肌梗死、心力衰竭、骨折、肺炎和急性肾损伤的风险增加相关，但与室性心律失常无关。不良结果的范围比之前在监管警报中强调的更广，在开始治疗后不久风险最高。

英文原文如下：

Abstracts

OBJECTIVE  To investigate risks of multiple adverse outcomes associated with use of antipsychotics in people with dementia.

DESIGN  Population based matched cohort study.

SETTING  Linked primary care, hospital and mortality data from Clinical Practice Research Datalink (CPRD), England.

POPULATION  Adults (≥50 years) with a diagnosis of dementia between 1 January 1998 and 31 May 2018 (n=173 910, 63.0% women). Each new antipsychotic user (n=35 339, 62.5% women) was matched with up to 15 non-users using incidence density sampling.

MAIN OUTCOME MEASURES  The main outcomes were stroke, venous thromboembolism, myocardial infarction, heart failure, ventricular arrhythmia, fracture, pneumonia, and acute kidney injury, stratified by periods of antipsychotic use, with absolute risks calculated using cumulative incidence in antipsychotic users versus matched comparators. An unrelated (negative control) outcome of appendicitis and cholecystitis combined was also investigated to detect potential unmeasured confounding.

RESULTS  Compared with non-use, any antipsychotic use was associated with increased risks of all outcomes, except ventricular arrhythmia. Current use (90 days after a prescription) was associated with elevated risks of pneumonia (hazard ratio 2.19, 95% confidence interval (CI) 2.10 to 2.28), acute kidney injury (1.72, 1.61 to 1.84), venous thromboembolism (1.62, 1.46 to 1.80), stroke (1.61, 1.52 to 1.71), fracture (1.43, 1.35 to 1.52), myocardial infarction (1.28, 1.15 to 1.42), and heart failure (1.27, 1.18 to 1.37). No increased risks were observed for the negative control outcome (appendicitis and cholecystitis). In the 90 days after drug initiation, the cumulative incidence of pneumonia among antipsychotic users was 4.48% (4.26% to 4.71%) versus 1.49% (1.45% to 1.53%) in the matched cohort of non-users (difference 2.99%, 95% CI 2.77% to 3.22%).

CONCLUSIONS  Antipsychotic use compared with non-use in adults with dementia was associated with increased risks of stroke, venous thromboembolism, myocardial infarction, heart failure, fracture, pneumonia, and acute kidney injury, but not ventricular arrhythmia. The range of adverse outcomes was wider than previously highlighted in regulatory alerts, with the highest risks soon after initiation of treatment.

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