Bleeding Risks Associated with Antidepressant Medications Among Acute Ischemic Stroke Patients on Anticoagulation or Dual Anti-platelet Therapy

Background Selective Serotonin and Serotonin-Norepinephrine Reuptake Inhibitors (SSRI/SNRIs) can treat post-stroke depression and improve recovery but may be withheld for acute ischemic stroke (AIS) patients over bleeding risk concerns. Study objectives were: 1) Quantify the association between early SSRI/SNRI initiation and adverse bleeding events 2) Assess bleeding risk among patients receiving concurrent anticoagulants (AC) or dual antiplatelet therapy (DAPT) and 3) Evaluate if bleeding risks were specific to SSRI/SNRIs. Methods AIS patients were identified from Electronic Medical Records of 76 healthcare organizations (2004-2024). Patients were assigned to one of three groups within 3 months of the indexed stroke – (1) No antidepressant (No AD), (2) SSRI/SNRI, (3) Other AD (i.e., mirtazapine, bupropion, trazodone, or tricyclic ADs). The primary outcome was 1-year risk of a major bleeding event. Secondary outcomes included hemorrhagic stroke (HS), fall/fracture and death. Baseline differences were adjusted for using 1:1 matched propensity scores. Results 679,532 patients were included [No AD (n=612,868), SSRI/SNRI (n=40,136), Other AD (n=26,528)]. Early SSRI/SNRIs use (vs. No ADs) was not associated with an increased risk of a major bleed among all patients (n=36,838 pairs) or patients on anticoagulants (n=7,942 pairs). Concurrent use of SSRI/SNRIs and DAPT was associated with an 11% increased risk of a major bleed (RR: 1.11, 95% CI: 1.00 -1.24, n=7,536 pairs). Bleed risks were higher (RR: 1.10; 95 CI% 1.05, 1.14) for use of Other AD vs. SSRI/SNRI (n=22,789 pairs). Discussion SSRI/SNRIs treat post-stroke depression, promote recovery and are generally safe, however, bleed risks among patients on current DAPT should be considered.