Antidepressant Agent Use and Risk of Bleeding in Patients with Cancer: Results from the Vienna CAT-BLED study

Introduction The coagulation system is dysregulated in cancer, leading to an increased risk of thrombosis and bleeding. Risk factors for bleeding in patients with cancer are poorly defined, limiting individual risk stratification. Antidepressant use is common in patients with cancer and has been linked to bleeding in non-cancer populations. We therefore aimed to assess bleeding risk associated with antidepressant use in patients with cancer. Method This analysis was conducted within the Vienna Cancer, Thrombosis and Bleeding (CAT-BLED) study, a prospective, single-center cohort study of cancer patients receiving systemic treatment at the Medical University of Vienna, Austria. At inclusion, electronic health records were reviewed for current medications; patients on therapeutic anticoagulation were excluded. Patients were followed for bleeding events, defined as major bleeding (MB), clinically relevant bleeding (CRB), and gastrointestinal CRB (GI-CRB), adjudicated by an independent expert committee. Twelve-month cumulative incidences were estimated with death as a competing event. Adjusted Fine-Gray models were used to evaluate associations between antidepressant use and bleeding. Results One-thousand-one-hundred-sixty-one patients were analyzed (median age 61 years [IQR: 53–69]; 52.7% female; [ Fig 2 ]). The most common cancers were lung (20.9%), breast (15.1%), and pancreatic (10.3%); 56.1% had metastatic disease, and 61.9% had newly diagnosed cancer. Most received chemotherapy (49.1%), chemotherapy with immune checkpoint inhibitors (17.7%), or chemotherapy with targeted agents (13.4%). At inclusion, 218 patients (18.8%) were receiving antidepressants: SSRIs in 91 (7.8%), SARIs in 75 (6.5%), other agents in 68 (5.9%), and SNRIs in 13 (1.1%); 16.6% received antiplatelet therapy, including 41 with concurrent antidepressant use. Median follow-up was 258 days (IQR: 126–506). During follow-up, 113 patients experienced CRB, 60 MB, and 50 GI-CRB, with 12-month cumulative incidences of 10.4% (95% confidence interval [CI]: 8.3-12.4), 6.5% (95% CI: 4.9-8.1), and 5.0% (95% CI: 3.6–6.5), respectively. Incidences were higher in antidepressant users than non-users (CRB: 12.3% vs 9.8%; MB: 11.7% vs 6.0%; GI-CRB: 13.2% vs 4.3%), driven by SSRI users (CRB: 18.6%, MB: 11.7%, GI-CRB: 13.2%; [ Fig. 1A-C ]). Fig. 1 12-month cumulative incidences of CRB (A), GI-CRB (B) and MB (C) stratified by SSRI use Twelve-month cumulative incidence of (A) clinically relevant bleeding (CRB), (B) gastrointestinal CRB (GI-CRB), and (C) major bleeding (MB) among patients receiving anticancer therapy, stratified by selective serotonin reuptake inhibitor (SSRI) use. Red curves represent patients receiving SSRIs; blue curves represent those not receiving SSRIs. Numbers at risk at each time point are shown below each panel. Fig. 2 Baseline characteristics In multivariable analysis (adjusted for age, sex, cancer type, stage, disease status, and antiplatelet therapy), SSRI use was associated with increased risk of CRB (SHR 2.11 [95% CI: 1.15–3.85]), MB (SHR 2.53 [95% CI: 1.24–5.54]), and GI-CRB (SHR 3.81 [95% CI: 1.78–8.17]). No significant associations were seen for other antidepressant classes. Concomitant SSRI and antiplatelet use further increased CRB risk (SHR 4.73 [95% CI: 1.72–12.97]). Conclusion Cancer patients receiving antidepressants, particularly SSRIs, had an increased bleeding risk. Concomitant antidepressant and antiplatelet use further heightened this risk, warranting further studies. Publication History Article published online: 17 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany