Use of serotonin reuptake inhibitor antidepressants and the risk of bleeding complications in patients on anticoagulant or antiplatelet agents: a systematic review and meta-analysis
Surapon Nochaiwong, Chidchanok Ruengorn, Ratanaporn Awiphan, Chatree Chai‐Adisaksopha, Apichat Tantraworasin, Chabaphai Phosuya, Penkarn Kanjanarat, Wilaiwan Chongruksut, Manish M. Sood, Kednapa Thavorn
Abstract
BACKGROUND: 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. METHODS: 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). RESULTS: = .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. CONCLUSIONS: 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. PROSPERO REGISTRATION: 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.