Perioperative selective serotonin reuptake inhibitor and serotonin-norepinephrine reuptake inhibitor use and 30-day bleeding after elective colectomy.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) impair platelet hemostasis, but their effect on bleeding after elective colectomy is unknown. METHODS: Using the TriNetX US Collaborative Network (2017-2024), adults undergoing elective colectomy were compared across six 1:1 propensity score-matched contrasts, each prespecified to address a distinct source of confounding: primary (SSRI/SNRI vs non-users), active-comparator (high-vs low-SERT affinity, for confounding by indication), class-specific (SSRI-only and SNRI-only vs non-users) and head-to-head (SNRI vs SSRI, for agent pooling), and incident new-user (for prevalent-user bias). The primary outcome was a 30-day bleeding composite. RESULTS: After matching, 8738 patients per arm comprised the primary cohort (all SMDs <0.10). SSRI/SNRI use raised 30-day bleeding (RR 1.29, 95% CI 1.11-1.50; NNH 104). Findings were consistent in SSRI-only (RR 1.22, 1.02-1.45), SNRI-only (RR 1.53, 1.15-2.04), and incident users (RR 1.29, 1.05-1.60). Active-comparator and head-to-head contrasts were non-significant. CONCLUSION: Perioperative SSRI/SNRI use is associated with a modest, bleeding-specific 30-day risk increase that persists in new initiators, supporting perioperative bleeding awareness without routine discontinuation.