Introduction Several small studies have reported inconsistent findings about the safety of selective serotonin reuptake inhibitors (SSRIs) among patients undergoing coronary artery bypass grafting (CABG). We sought to investigate post-CABG bleeding and mortality outcomes related to antidepressant exposure. Methods We identified patients who underwent CABG between 2004 and 2008 in the Premier Perspective Comparative Database. We determined whether they received SSRIs, other antidepressants, or no antidepressants on any pre-CABG hospital day and used Cox proportional hazards models to compare bleeding and mortality rates among the exposure groups while adjusting for potential confounders based on administrative data, pre-CABG charge codes, and discharge diagnosis codes. Results We identified 132,686 eligible patients: 7112 exposed to SSRIs, 1905 exposed to other antidepressants, and 123,668 unexposed. As compared with no exposure, neither SSRIs (hazard ratio [HR] 0.98; 95 % confidence interval [CI] 0.90–1.07) nor other antidepressants (HR 1.11; 95 % CI 0.96–1.28) increased major bleeds, and neither SSRIs (HR 0.93; 95 % CI 0.80–1.07) nor other antidepressants (HR 0.84; 95 % CI 0.62–1.14) increased mortality. Both SSRIs (HR 1.14; 95 % CI 1.10–1.18) and other antidepressants (HR 1.11; 95 % CI 1.03–1.19) were associated with a slight increase in receipt of one or more packed red blood cell (pRBC) units, but neither were associated with substantial increases in receipt of three or more pRBC units (HR 1.06; 95 % CI 0.96–1.17 for SSRIs; HR 1.09; 95 % CI 0.91–1.31 for other antidepressants). Conclusion In this large cohort study, neither SSRIs nor other antidepressants were associated with elevated rates of major bleed, or in-hospital mortality.
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