Concomitant selective serotonin reuptake inhibitors and oral anticoagulants may increase risk of bleeding

1. This case-control study found that in patients with atrial fibrillation concomitant Serotonin Reuptake Inhibitor (SSRI) and Oral Anticoagulants (OAC) was associated with an increased risk of major bleeding compared with OAC use alone.

2. This increased risk was highest in the first 30 days of continuous, concomitant use.

Evidence Rating Level:  2 (Good)

Antidepressants, especially SSRIs, are widely prescribed, raising concerns about their interaction with OACs and the risk of major bleeding. Utilizing the UK Clinical Practice Research Datalink, this case-control study investigated whether concomitant SSRIs and OACs use was associated with the risk of major bleeding compared with OAC use alone among patients with AF. 331 305 patients with an incident diagnosis of AF between January, 1998, and March, 2021 and a prescription for an OAC (apixaban, dabigatran, edoxaban, rivaroxaban, or warfarin) after AF diagnosis were identified. 42 190 patients (mean [SD] age, 74.2 [9.3] years; 59.8% men) were identified as cases—patients with a first recorded diagnosis of major bleeding during follow-up—and were matched to 1 156 641 controls (mean [SD] age, 74.2 [9.3] years; 59.8% men). Concomitant SSRIs and OACs use was associated with a 33% higher risk of major bleeding compared to OAC use alone (IRR: 1.33; 95% CI: 1.24-1.42). The risk peaked within the initial 30 days of continuous use (IRR: 1.74; 95% CI: 1.37-2.22) and declined afterward. Age, sex, history of major bleeding, chronic kidney disease, and SSRI potency did not alter the risk. Moreover, the risk remained elevated for concomitant SSRIs with both DOACs (IRR: 1.25; 95% CI: 1.12-1.40) and VKAs (IRR: 1.36; 95% CI: 1.25-1.47) compared to DOACs and VKAs alone, respectively. Overall, these findings suggest that concomitant SSRI and OAC use was associated with an increased risk of major bleeding compared with OAC use alone, underscoring the need for close monitoring, especially during initial SSRI-OAC use, to mitigate bleeding risks.

Click to read the study in JAMA Network Open

Image: PD

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