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.
| Discipline Area | Score |
|---|---|
| Family Medicine (FM)/General Practice (GP) |  |
| General Internal Medicine-Primary Care(US) | |
| Internal Medicine | |
| Geriatrics | |
| Psychiatry | |
The many studies on SSRIs causing risk for bleeding vary from no increase to a small relative or very small absolute risk. This new nationwide study provides another reassuring view.
As a geriatric psychiatrist, I treat many patients who are concomitantly on an SSRI and anticoagulant. We know that SSRIs and antithrombotic agents independently increase bleeding risk, but I was previously unaware that, taken together, they do not cause a further increase in bleeding risk. This information will help with risk/benefit discussions and decisions for patients with clinical indications for both types of medications. Further replication studies are warranted.
This very interesting case–case-time-control study found no statistically significant increase in major bleeding with concomitant SSRI plus anticoagulant or antiplatelet use after adjusting for secular SSRI prescribing trends. The crude within-person case-crossover analyses suggested elevated risk, but this disappeared with exposure time-trend bias correction. Findings caution reflexive SSRI avoidance in patients needing antithrombotics, while still emphasising individualized bleeding risk assessment rather than assuming a large independent SSRI effect.
