Risk of major bleeding events associated with concomitant use of selective serotonin reuptake inhibitors and anti-thrombotic drugs: a nationwide case–case-time-control study

Abstract Background Depression is common in older adults, who are also at elevated risk of bleeding due to age-related physiological changes and comorbidities. Concerns have been raised regarding potential bleeding risk from concomitant use of selective serotonin reuptake inhibitors (SSRIs) and antithrombotic agents. Objective To assess whether the risk of major bleeding is associated with the concomitant use of SSRIs and antithrombotic agents. Design Case–case-time-control. Method We included individuals prescribed both SSRIs and antithrombotics who were newly diagnosed with major bleeding. To adjust for exposure time trend, each patient who experienced a major bleeding was matched with future cases who had not yet experienced bleeding, by age, sex and cohort entry date. Conditional logistic regression was used to estimate adjusted odds ratio (aOR) and 95% confidence interval (CI) for risk period compared with five control periods. Results Among SSRIs and anticoagulant users, 110 540 were matched with future cases (mean age 67.7 years; 49.7% female). After accounting for the time-trends in exposure, concomitant use did not significantly increase the risk of major bleeding (aOR 1.07, 95% CI 0.89–1.28). Similarly, among SSRIs and antiplatelet users, 105 464 patients were matched (mean age 58.6 years; 48.6% female), and no significant increase in bleeding risk was observed (aOR 1.10, 95% CI 0.88–1.38). The subgroup analyses stratified by sex and age were consistent with the main results. Conclusion No significant increase in the major bleeding risk was observed with concomitant use of SSRIs and antithrombotic agents. However, clinicians should consider individual risk–benefit assessments when prescribing these combinations.