S1384 Invisible Risk: Gastrointestinal Bleeding Linked to SSRI Use—A Literature Review

Introduction: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for depression and anxiety, but growing evidence suggests a potential risk of gastrointestinal (GI) bleeding associated with their use. Serotonin is a key mediator in platelet aggregation, and SSRIs may impair hemostasis by depleting platelet serotonin. This review explores current findings on the relationship between SSRI use and GI bleeding to guide safer prescribing practices. Methods: A systematic literature search was conducted across medical databases and curated sources. Of 192 initially identified articles, 13 met inclusion criteria for qualitative review. Studies were selected based on relevance, inclusion of human subjects, focus on SSRI-related bleeding risk, and availability of clinical or quantitative outcomes. Exclusion criteria included non-English language, animal studies, and lack of bleeding-related endpoints. Results: The 13 included studies consistently identified an increased risk of upper GI bleeding with SSRI use. Several found a dose-response relationship, while others highlighted amplified risk when SSRIs were taken concurrently with nonsteroidal anti-inflammatory drugs (NSAIDs) or anticoagulants. One study demonstrated that the risk was specific to SSRIs and not shared by SNRIs. A few reports showed that co-administration of proton pump inhibitors (PPIs) reduced the incidence of GI bleeding. Notably, SSRIs independently increased bleeding risk even without other contributing medications, reinforcing serotonin’s role in platelet dysfunction. Conclusion: This review supports a clinically significant association between SSRIs and GI bleeding. The effect is biologically plausible and appears dose-related, with additive risk from common medications such as NSAIDs. Co-prescribing gastroprotective agents like PPIs may mitigate harm. Clinicians should weigh benefits against bleeding risks, especially in high-risk populations, and consider the lowest effective SSRI dose when possible. More prospective studies are needed to refine risk stratification and preventive strategies.