Serotonergic Antidepressant Use and Risk of Clinically Significant Bleeding in Thrombocytopenic Hematologic Malignancy Patients

Background: Serotonin reuptake inhibitor (SRI) antidepressants have known antiplatelet properties. Patients with hematologic malignancies (HMs) are at an increased risk of bleeding complications due to their malignancy and treatment-induced thrombocytopenia. Objective: The purpose of this study was to evaluate the risk of clinically significant bleeding (CSB) in patients with HM and thrombocytopenia who are prescribed SRIs. Methods: This retrospective cohort study included adult patients admitted to the hospital with HM and thrombocytopenia. Patients were stratified into SRI-exposed and SRI-unexposed groups. Patients were followed up until resolution of thrombocytopenia, hospital discharge, death, or SRI therapy interruption. The primary outcome was the incidence of CSB. Results: A total of the 324 patients were included in the study (119 SRI exposed vs 205 SRI unexposed). The median baseline platelet value was 35 × 10⁹/L and 31 × 10⁹/L, respectively. The median platelet nadir was 6 × 10⁹/L, and the median duration of study inclusion was 12 days in both groups. No difference was seen in the incidence of CSB between groups (16% vs 13%, P = 0.487). Hospital length of stay (LOS) (20 vs 19 days, P = 0.227) and intensive care unit (ICU) LOS (3.9 vs 3.9 days, P = 0.996) were similar between groups. On multivariable analysis, SRI exposure was not independently associated with CSB (adjusted odds ratio [aOR] = 1.46, 95% confidence interval [CI] 0.75-2.86). Conclusion and Relevance: In patients with HM and thrombocytopenia, SRI exposure was not associated with an increased risk of CSB. Given the small study size, assessment of patient-specific risks versus benefits should still be considered when prescribing SRI therapy in this patient population.