Serotonin reuptake inhibitor (SRI) users were linked with the risk of bleeding complications in comparison with non-SRI users, with concurrent antithrombotic use. The risk was consistently elevated across the types of bleeding events (gastrointestinal bleeding, major bleeding, or any bleeding events), whereas only anticoagulant usage was related to intracranial haemorrhage, according to a systematic review and meta-analysis. Researchers sought to investigate the effects of SRI and the risk of bleeding problems among patients undergoing antithrombotic treatment.

For relevant data searches, grey literature (Google Scholar and preprint reports), CINAHL, Scopus, Web of Science, Cochrane Library, PsycINFO, PubMed, Embase, and Medline were explored with no language restrictions. Major bleeding was the key endpoint. Any bleeding incidents, gastrointestinal bleeding, and intracranial bleeding were the secondary endpoints ascertained. The odds ratios (ORs) and 95% confidence intervals were calculated using a random-effects model meta-analysis.

Although no randomized studies were discovered, 32 non-randomized studies (cohort or case-control) with 1,848,285 subjects were incorporated in the meta-analysis that fit the study selection criteria. SRI users had a statistically significant elevated risk of severe bleeding contrasted to non-SRI users among those taking anticoagulants (13 trials). The pooled OR was 1.39 (moderate heterogeneity).

SRI users had a higher risk of major bleeding among those on antiplatelet treatment (2 trials); the pooled OR was 1.45 (low heterogeneity). Regarding secondary outcomes, the utilization of SRI in patients receiving antithrombotic medication demonstrated a greater risk of gastrointestinal bleeding or any bleeding events. However, only the use of anticoagulants was shown to raise the risk of intracranial haemorrhage.

SRI antidepressants are linked to an increased bleeding complication risk in subjects receiving antithrombotic treatment, indicating that caution should be warranted while co-prescribing.