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Meta-Analysis
. 2022 Dec;54(1):80-97.
doi: 10.1080/07853890.2021.2017474.

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  1   2 , Chidchanok Ruengorn  1   2 , Ratanaporn Awiphan  1   2 , Chatree Chai-Adisaksopha  3 , Apichat Tantraworasin  2   4 , Chabaphai Phosuya  1 , Penkarn Kanjanarat  1   2 , Wilaiwan Chongruksut  2   4 , Manish M Sood  5   6 , Kednapa Thavorn  2   5   7
Affiliations
Free PMC article
Meta-Analysis

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 et al. Ann Med. 2022 Dec.
Free PMC article

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: 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; p < .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; p = .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.

Keywords: Anticoagulation; antidepressant; antiplatelet; bleeding complications; meta-analysis; serotonin-reuptake inhibitors.

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Conflict of interest statement

All authors declare no competing interests. All the researchers involved performed this study in the context of their research.

Figures

Figure 1.
Figure 1.
Study selection flowchart.
Figure 2.
Figure 2.
Effect of the use of SRI concomitant with antithrombotic therapy and the risk of major bleeding. Individuals treated with (A) anticoagulant therapy or (B) antiplatelet therapy. CI: confidence interval; NA: not applicable; SRI: serotonin reuptake inhibitor.
Figure 3.
Figure 3.
Effect of the use of SRI concomitant with antithrombotic therapy and the risk of intracranial haemorrhage. Individuals treated with (A) anticoagulant therapy or (B) antiplatelet therapy. CI: confidence interval; NA: not applicable; SRI: serotonin reuptake inhibitor.
Figure 4.
Figure 4.
Effect of the use of SRI concomitant with antithrombotic therapy and the risk of gastrointestinal bleeding. Individuals treated with (A) anticoagulant therapy or (B) antiplatelet therapy. CI: confidence interval; NA: not applicable; SRI: serotonin reuptake inhibitor.
Figure 5.
Figure 5.
Effect of the use of SRI concomitant with antithrombotic therapy and the risk of any bleeding events. Individuals treated with (A) anticoagulant therapy or (B) antiplatelet therapy. CI: confidence interval; NA: not applicable; SRI: serotonin reuptake inhibitor.
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Grants and funding

This work was funded by the Faculty of Pharmacy and partially supported by the Pharmacoepidemiology and Statistics Research Centre (PESRC) through the Chiang Mai University, Thailand. The funder of the study had no role in the study design collection, analysis, or interpretation of the data, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit it for publication. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the funders.