Quantifying the Role of Adverse Events in the Mortality Difference between First and Second-Generation Antipsychotics in Older Adults: Systematic Review and Meta-Synthesis
Quantifying the Role of Adverse Events in the Mortality Difference between First and Second-Generation Antipsychotics in Older Adults: Systematic Review and Meta-Synthesis
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DOI：
10.1371/journal.pone.0105376
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发表时间：
2014-08-20
期刊：
影响因子：
3.7
通讯作者：
Blacker, Deborah
中科院分区：
文献类型：
--
作者：
Jackson, John W.;Schneeweiss, Sebastian;Blacker, Deborah
背景：观察性研究报道，与第二代抗精神病药物（SGAs）相比，第一代抗精神病药物（FGAs）治疗的老年人死亡率更高。一些研究检查了医疗事件的风险，包括中风、室性心律失常、静脉血栓栓塞、心肌梗死、肺炎和髋部骨折。目的：1)回顾强有力的流行病学证据，比较老年人FGAs和SGAs的死亡率和医疗事件风险；2)量化这些医疗事件在多大程度上解释了FGAs和SGAs之间观察到的死亡率差异。数据来源：Pubmed和Science Citation Index。研究资格标准、参与者和干预措施：抗精神病药物使用者的研究：1)评估死亡率或上述医疗事件；2)仅限于平均年龄在65岁或以上的人群3)将FGAs与SGAs进行比较，或将两者都与非用户组进行比较；(4)采用“新用户”设计；(5)调整抗精神病药物起始前评估的混杂因素；(6)并且在抗精神病药物开始后不需要生存。对与指定医疗事件相关的死亡率估计值进行了单独搜索。研究评价和综合方法：对于每个医疗事件，我们使用非参数模型来估计死亡率差异比例的下界和上界-比较FGAs和sgas在医疗事件风险差异中介导的死亡率差异。结果：我们对纳入的研究和这些机制的生物学合理性进行了简要的总结。在检索到的1122个独特引用中，我们回顾了20个观察性队列研究，其中报告了28个关联。我们确定髋部骨折、中风、心肌梗死和室性心律失常是从抗精神病药物类型到死亡的因果通路上的潜在中介。然而，这些事件似乎并不能解释整个死亡率差异。结论：目前的文献表明，髋部骨折、卒中、心肌梗死和室性心律失常可以部分解释SGAs和FGAs之间的死亡率差异。
Background: Observational studies have reported higher mortality among older adults treated with first-generation antipsychotics (FGAs) versus second-generation antipsychotics (SGAs). A few studies examined risk for medical events, including stroke, ventricular arrhythmia, venous thromboembolism, myocardial infarction, pneumonia, and hip fracture.Objectives: 1) Review robust epidemiologic evidence comparing mortality and medical event risk between FGAs and SGAs in older adults; 2) Quantify how much these medical events explain the observed mortality difference between FGAs and SGAs.Data sources: Pubmed and Science Citation Index.Study eligibility criteria, participants, and interventions: Studies of antipsychotic users that: 1) evaluated mortality or medical events specified above; 2) restricted to populations with a mean age of 65 years or older 3) compared FGAs to SGAs, or both to a non-user group; (4) employed a "new user" design; (5) adjusted for confounders assessed prior to antipsychotic initiation; (6) and did not require survival after antipsychotic initiation. A separate search was performed for mortality estimates associated with the specified medical events.Study appraisal and synthesis methods: For each medical event, we used a non-parametric model to estimate lower and upper bounds for the proportion of the mortality difference-comparing FGAs to SGAs-mediated by their difference in risk for the medical event.Results: We provide a brief, updated summary of the included studies and the biological plausibility of these mechanisms. Of the 1122 unique citations retrieved, we reviewed 20 observational cohort studies that reported 28 associations. We identified hip fracture, stroke, myocardial infarction, and ventricular arrhythmias as potential intermediaries on the causal pathway from antipsychotic type to death. However, these events did not appear to explain the entire mortality difference.Conclusions: The current literature suggests that hip fracture, stroke, myocardial infarction, and ventricular arrhythmias partially explain the mortality difference between SGAs and FGAs.