Jensen Melanie P, Ziff Oliver J, Banerjee Gargi, Ambler Gareth, Werring David J
Stroke Research Centre, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London, UK.
Department of Statistical Science, UCL, London, UK.
Eur Stroke J. 2019 Jun;4(2):144-152. doi: 10.1177/2396987319827211. Epub 2019 Jan 25.
Observational studies have suggested increased risk of intracranial haemorrhage (ICrH) in patients receiving selective serotonin reuptake inhibitors (SSRIs). We sought to clarify the impact of SSRIs on ICrH, accounting for study methodology.
A comprehensive search of Medline, Embase and the Cochrane Library from 1960 to December 2017 identified studies comparing SSRIs with control. The outcomes (first-ever and recurrent ICrH) were meta-analysed using a random effects model.
Twenty-four observational studies and three randomised trials were available for meta-analysis, totalling 4,844,090 patient-years of follow-up. Those receiving SSRIs were more likely to be female ( = 0.01) and have depression ( < 0.001). Compared to controls, SSRI users had a significantly increased risk of ICrH (relative risk (RR) 1.26, 95%CI 1.11-1.42). Although SSRI use was associated with increased ICrH risk in those without previous ICrH (RR 1.31, 95%CI 1.15-1.48), this was not the case in those with previous ICrH (RR 0.95, 95%CI 0.83-1.09). Sensitivity analysis according to the bleeding definition reported demonstrated that although 'haemorrhagic stroke' was associated with SSRIs (RR 1.40, 95%CI 1.13-1.72), intracerebral haemorrhage was not (RR 1.11, 95%CI 0.86-1.42). Additional sensitivity analyses demonstrated a stronger association between SSRIs and ICrH in studies with a high ( < 0.001) compared to low risk of bias ( = 0.09) and with retrospective ( < 0.001) compared to prospective (p=0.31) study designs.
Although SSRIs are associated with an increased risk of ICrH, the association is partly accounted for by important biases and other methodological limitations in the available observational data.
Our findings suggest there is insufficient high-quality data to advise restriction of SSRIs because of concern regarding ICrH risk.
观察性研究表明，接受选择性5-羟色胺再摄取抑制剂（SSRI）治疗的患者发生颅内出血（ICrH）的风险增加。我们试图阐明SSRI对ICrH的影响，并考虑研究方法。
对1960年至2017年12月期间的Medline、Embase和Cochrane图书馆进行全面检索，以确定比较SSRI与对照的研究。使用随机效应模型对结果（首次和复发性ICrH）进行荟萃分析。
有24项观察性研究和3项随机试验可用于荟萃分析，随访时间总计4,844,090患者年。接受SSRI治疗的患者更可能为女性（P = 0.01）且患有抑郁症（P < 0.001）。与对照组相比，使用SSRI的患者发生ICrH的风险显著增加（相对风险（RR）1.26，95%置信区间1.11 - 1.42）。尽管在既往无ICrH的患者中使用SSRI与ICrH风险增加相关（RR 1.31，95%置信区间1.15 - 1.48），但在既往有ICrH的患者中并非如此（RR 0.95，95%置信区间0.83 - 1.09）。根据所报告的出血定义进行的敏感性分析表明，尽管“出血性卒中”与SSRI相关（RR 1.40，95%置信区间1.13 - 1.72），但脑出血并非如此（RR 1.11，95%置信区间0.86 - 1.42）。额外的敏感性分析表明，与低偏倚风险（P = 0.09）的研究相比，在高偏倚风险（P < 0.001）的研究中，SSRI与ICrH之间的关联更强；与前瞻性（P = 0.31）研究设计相比，在回顾性（P < 0.001）研究设计中，SSRI与ICrH之间的关联更强。
尽管SSRI与ICrH风险增加相关，但这种关联部分可归因于现有观察性数据中的重要偏倚和其他方法学局限性。
我们的研究结果表明，由于担心ICrH风险，没有足够的高质量数据来建议限制使用SSRI。
