The Relationship Between Selective Serotonin Reuptake Inhibitor Use and Delayed Bleeding After Colorectal Endoscopic Resection: A Nationwide Retrospective Cohort Study.

PURPOSE: Selective serotonin reuptake inhibitors (SSRIs) are associated with an increased risk of gastrointestinal bleeding. However, their effect on delayed bleeding after colorectal endoscopic resection (CER) remains unclear. We evaluated the association between SSRI Use and delayed bleeding risk in patients undergoing CER. METHODS: We conducted a retrospective cohort study using a nationwide Japanese database from January 2009 to August 2023. Patients undergoing CER were classified into SSRI and non-SSRI groups. The primary outcome was 30-day delayed bleeding. Inverse probability of treatment weighting (IPTW) targeting the average treatment effect among SSRI users (ATT-IPTW) was used to balance age, sex, dialysis, antithrombotic drug use, NSAID use, procedure type, liver disease, coagulation disorder, and platelet disorder. RESULTS: The final cohort included 169,995 patients (2454 SSRI users and 167,541 non-SSRI users). After ATT-IPTW, all included covariates had absolute standardized mean differences <0.10. Weighted delayed bleeding incidence was 0.77% in SSRI users and 0.69% in non-SSRI users (OR, 1.12; 95% CI, 0.71-1.77; P = 0.62). No statistically significant interaction was observed between SSRI and NSAID use (P for interaction = 0.71). Findings were similar across sensitivity analyses. CONCLUSION: No statistically significant association was detected between SSRI use and delayed bleeding after CER. However, the limited number of bleeding events and wide confidence interval preclude exclusion of a clinically meaningful moderate increase in risk, and these findings should not be interpreted as evidence of safety or equivalence. Further evidence is needed, particularly for ESD and resection of large lesions.