Abstract Body (Do not enter title and authors here): Background: Selective serotonin/serotonin-norepinephrine reuptake inhibitors (SSRI/SNRIs) are associated with improved stroke recovery. Some clinicians withhold SSRI/SNRIs over bleeding risk concerns. Our objectives were: 1) Quantify the association between early initiation of SSRI/SNRIs and adverse bleeding events among acute ischemic stroke (IS) patients, 2) Determine bleeding risks among patients receiving anticoagulation (AC) or dual antiplatelet therapy (DAPT), and 3) Evaluate bleeding risks between anti-depressant (AD) classes.
Methods: Medication naïve first-time IS patients were identified from Electronic Medical Records of 70 healthcare organizations (2003-2023). Patients without ADs were considered “No AD”. Patients started on ADs within 3 months of the indexed stroke were classified as "SSRI/SNRI" or "Other AD" (i.e., Mirtazapine, bupropion, trazodone, or tricyclic ADs). The primary outcome was 1-year risk of major bleeding events (e.g., gastrointestinal/intracranial or shock). Secondary outcomes were hemorrhagic stroke (HS), fall and death. Baseline differences were adjusted for using 1:1 matched propensity scores.
Results: A total of n=666,150 patients were included [No AD (n=607,278), SSRI/SNRI (n=35,631), Other AD (n=23,241)]. Early use of SSRI/SNRIs (vs. No ADs) was not associated with an increased risk of a major bleed for all patients (n=35,557 matched pairs) or among patients on AC (n=7,672 matched pairs). However, concurrent use of SSRI/SNRIs and DAPT was associated with a 29% increased risk of HS (RR:1.29, 95% CI: 1.11-1.50, n=8,381 matched pairs). Among patients on ADs, bleed risks were higher for use of “Other ADs” vs. "SSRI/SNRIs" (n=21,810 matched pairs).
Discussion: SSRI/SNRIs treat post-stroke depression, promote functional recovery and are generally safe to start during the early stages of recovery for patients with IS. However, an increased risk of HS should be considered when starting ADs among patients on DAPT.