Pharmacovigilance Analysis of Bleeding Events Associated With Selective Serotonin Reuptake Inhibitors (SSRIs) Using the US Food and Drug Administration Adverse Event Reporting System (FAERS).
背景 选择性5-羟色胺再摄取抑制剂（SSRIs）常用于治疗抑郁和焦虑障碍，并可能增加出血风险。然而，关于SSRI相关出血的模式和分布，全面的真实世界数据仍然有限。本研究旨在利用大规模药物警戒数据，描述与各SSRI相关的出血不良事件特征。方法 采用回顾性、描述性药物警戒研究，数据来源于美国食品药品监督管理局不良事件报告系统（FAERS），检索时间范围为2004年第一季度至2025年第四季度。筛选以舍曲林、西酞普兰、艾司西酞普兰、氟西汀、帕罗西汀或氟伏沙明为可疑药物的报告，并使用《监管活动医学词典》（MedDRA）的系统器官分类（SOC）“血管疾病”及高位组语（HLGT）“血管出血性疾病NEC”进行过滤。出血事件在首选语（PT）层面进行汇总。对人口学特征、地理分布、出血部位以及与出血风险相关药物的合并使用情况进行描述性分析。结果 在总共380,241例FAERS病例中，共识别出5,604例出血相关病例。不同SSRI的出血事件发生率存在差异：艾司西酞普兰（2.85%）、西酞普兰（1.93%）、帕罗西汀（1.29%）、舍曲林（1.25%）、氟伏沙明（1.05%）和氟西汀（1.02%）。舍曲林的出血报告绝对数量最多（1,352例，24.1%），其次为艾司西酞普兰（1,229例，21.9%）和西酞普兰（1,029例，18.4%）。在年龄数据可用的病例中，>65岁患者构成最大群体（范围：17.1%-46.6%），其次为18-65岁成人（范围：11.0%-24.0%）。女性患者占多数（2,926例，52.2%）。出血（未特指）是最常报告的事件（范围：5.99%-15.93%），其次为挫伤（0.70%-10.24%）和血肿（1.25%-4.52%）。胃肠道（GI）出血事件，包括胃肠道出血（0.37%-1.45%）和直肠出血（0.31%-5.94%），以及中枢神经系统出血，包括脑出血（0.40%-1.27%）和蛛网膜下腔出血（0.35%-1.16%），均有持续报告。541例（9.7%）记录了合并使用增加出血风险的药物，其中抗血小板药物最常见（246例，4.4%），其次为非甾体抗炎药（NSAIDs）（143例，2.6%）、直接口服抗凝药（DOACs）（130例，2.3%）和华法林（22例，0.4%）。结论 这项基于FAERS的分析表明，出血是SSRIs类药物的整体安全性问题。FAERS数据中出血模式存在差异；然而，这些发现属于描述性结果，不应被解释为比较性风险差异。这些发现强调了个体化风险评估、仔细的药物核对以及加强药物警戒的重要性，以支持在常规临床实践中更安全地处方SSRI。
Background Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for depressive and anxiety disorders and may increase the risk of bleeding. However, comprehensive real-world data on the patterns and distribution of SSRI-related bleeding remain limited. This study aimed to characterize bleeding adverse events associated with individual SSRIs using large-scale pharmacovigilance data. Methods A retrospective, descriptive pharmacovigilance study was conducted using data from the US Food and Drug Administration Adverse Event Reporting System (FAERS), retrieved from the first quarter of 2004 to the fourth quarter of 2025. Reports containing sertraline, citalopram, escitalopram, fluoxetine, paroxetine, or fluvoxamine as suspect drugs were identified and filtered using the Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC) "Vascular disorders" and the High-Level Group Term (HLGT) "Vascular hemorrhagic disorders NEC". Bleeding events were summarized at the Preferred Term (PT) level. Descriptive analyses were performed for demographic characteristics, geographic distribution, bleeding sites, and concomitant use of medications associated with bleeding risk. Results A total of 5,604 bleeding-related cases were identified across 380,241 total FAERS cases. Bleeding event rates varied by SSRI: escitalopram (2.85%), citalopram (1.93%), paroxetine (1.29%), sertraline (1.25%), fluvoxamine (1.05%), and fluoxetine (1.02%). Sertraline accounted for the highest absolute number of bleeding reports (1,352, 24.1%), followed by escitalopram (1,229, 21.9%) and citalopram (1,029, 18.4%). Among the cases with available age data, patients aged >65 years constituted the largest group (range: 17.1%-46.6%), followed by adults aged 18-65 years (range: 11.0%-24.0%). Female patients were predominant (2,926, 52.2%). Hemorrhage (unspecified) was the most frequently reported event (range: 5.99%-15.93%), followed by contusion (0.70%-10.24%) and hematoma (1.25%-4.52%). Gastrointestinal (GI) bleeding events, including GI hemorrhage (0.37%-1.45%) and rectal hemorrhage (0.31%-5.94%), and central nervous system bleeding, including cerebral hemorrhage (0.40%-1.27%) and subarachnoid hemorrhage (0.35%-1.16%), were consistently reported. Concomitant use of medications increasing bleeding risk was documented in 541 cases (9.7%), with antiplatelet agents being most frequent (246, 4.4%), followed by nonsteroidal anti-inflammatory drugs (NSAIDs) (143, 2.6%), direct oral anticoagulants (DOACs) (130, 2.3%), and warfarin (22, 0.4%). Conclusion This FAERS-based analysis demonstrated that bleeding represented a class-wide safety concern among SSRIs. There were differences in bleeding patterns within the FAERS data; however, these findings are descriptive and should not be interpreted as comparative risk differences. These findings underscore the importance of individualized risk assessment, careful medication reconciliation, and strengthened pharmacovigilance to support safer SSRI prescription in routine clinical practice.
Adrian Chin Yan Chan. Pharmacovigilance Analysis of Bleeding Events Associated With Selective Serotonin Reuptake Inhibitors (SSRIs) Using the US Food and Drug Administration Adverse Event Reporting System (FAERS).. Cureus. 2026; doi:10.7759/cureus.110163.
Adrian Chin Yan Chan (2026). Pharmacovigilance Analysis of Bleeding Events Associated With Selective Serotonin Reuptake Inhibitors (SSRIs) Using the US Food and Drug Administration Adverse Event Reporting System (FAERS).. Cureus. https://doi.org/10.7759/cureus.110163
Adrian Chin Yan Chan. Pharmacovigilance Analysis of Bleeding Events Associated With Selective Serotonin Reuptake Inhibitors (SSRIs) Using the US Food and Drug Administration Adverse Event Reporting System (FAERS).[J]. Cureus, 2026 doi:10.7759/cureus.110163.
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