Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand.
Pharmacoepidemiology and Statistics Research Center (PESRC), Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand.
Ann Med. 2022 Dec;54(1):80-97. doi: 10.1080/07853890.2021.2017474.
Serotonin reuptake inhibitor (SRI) antidepressants are implicated in increasing the risk of bleeding among users; however, the comparative increase in bleeding risk with concurrent antithrombotic therapy (anticoagulant or antiplatelet) remains unclear. As such, we performed a systematic review and meta-analysis of all available evidence to evaluate the effects of SRI and the risk of bleeding complications among patients receiving antithrombotic therapy.
We searched Medline, Embase, PubMed, PsycINFO, Cochrane Library, Web of Science, Scopus, CINAHL, and grey literature (Google Scholar and preprint reports) up to 26 November, 2020, with no language restrictions (updated on 31 July 2021). The primary outcome of interest was major bleeding. Secondary outcomes included intracranial haemorrhage, gastrointestinal bleeding, and any bleeding events. We used a random-effects model meta-analysis to estimate the odds ratios (ORs) and 95% confidence intervals (CIs).
We did not identify any randomised studies but found 32 non-randomized studies (cohort or case-control) with 1,848,285 patients that fulfilled the study selection criteria and were included in the meta-analysis. Among individuals receiving anticoagulants (13 studies), SRI users experienced a statistically higher risk of major bleeding compared to non-SRI users: pooled OR was 1.39 (95% CI, 1.23-1.58; < .001; moderate heterogeneity). Among individuals receiving antiplatelet therapy (2 studies), SRI users were associated with an increased risk of major bleeding: pooled OR was 1.45 (95% CI, 1.17-1.80; = .001; low heterogeneity). For secondary outcomes, the use of SRI among individuals treated with antithrombotic therapy revealed a higher risk of gastrointestinal bleeding or any bleeding events, whereas only anticoagulant use was illustrated an increased risk of intracranial haemorrhage.
The use of SRI antidepressants among patients treated with antithrombotic therapy (either anticoagulant or antiplatelet) is associated with a higher risk of bleeding complications, suggesting that caution is warranted in co-prescription.
CRD42018083917KEY MESSAGESIn this meta-analysis of 32 non-randomized studies, SRI users were associated with the risk of bleeding complications compared to non-SRI users, with concurrent antithrombotic use (either anticoagulant or antiplatelet).The risk was consistently elevated across types of bleeding events (major bleeding, gastrointestinal bleeding, or any bleeding events), whereas only anticoagulant use was associated with intracranial haemorrhage.To promote the rational use of medicines, our findings suggest that the risk-benefit ratio must account for the clear efficacy of SRI against safety concerns in terms of bleeding risks.
选择性 5-羟色胺再摄取抑制剂（SSRIs）抗抑郁药被认为会增加使用者出血的风险；然而，同时使用抗血栓治疗（抗凝或抗血小板）时出血风险的增加仍不清楚。因此，我们进行了一项系统评价和荟萃分析，以评估所有可用证据中 SSRIs 的作用以及接受抗血栓治疗的患者发生出血并发症的风险。
我们检索了 Medline、Embase、PubMed、PsycINFO、Cochrane 图书馆、Web of Science、Scopus、CINAHL 和灰色文献（Google Scholar 和预印本报告），截至 2020 年 11 月 26 日，无语言限制（2021 年 7 月 31 日更新）。主要结局是主要出血。次要结局包括颅内出血、胃肠道出血和任何出血事件。我们使用随机效应模型荟萃分析来估计比值比（OR）和 95%置信区间（CI）。
我们没有发现任何随机研究，但发现了 32 项非随机研究（队列或病例对照），共纳入了 1848285 名符合研究选择标准并纳入荟萃分析的患者。在接受抗凝剂治疗的患者中（13 项研究），与非 SSRIs 使用者相比，SSRIs 使用者发生主要出血的风险更高：汇总 OR 为 1.39（95%CI，1.23-1.58；<0.001；中度异质性）。在接受抗血小板治疗的患者中（2 项研究），SSRIs 使用者发生主要出血的风险增加：汇总 OR 为 1.45（95%CI，1.17-1.80；=0.001；低异质性）。对于次要结局，抗血栓治疗中使用 SSRIs 显示胃肠道出血或任何出血事件的风险增加，而仅抗凝剂使用显示颅内出血的风险增加。
在接受抗血栓治疗（抗凝或抗血小板）的患者中使用 SSRIs 抗抑郁药与出血并发症的风险增加相关，这表明在联合处方时应谨慎。
PROSPERO 注册号：CRD42018083917
在这项对 32 项非随机研究的荟萃分析中，与非 SSRIs 使用者相比，SSRIs 使用者在同时使用抗血栓药物（无论是抗凝剂还是抗血小板药物）时发生出血并发症的风险增加。
这种风险在各种出血事件（主要出血、胃肠道出血或任何出血事件）中持续升高，而仅抗凝剂使用与颅内出血相关。
为了促进合理用药，我们的研究结果表明，在考虑 SSRIs 对抗出血风险的安全性问题时，必须考虑到其明确的疗效和获益风险比。
