Antidepressants and Postoperative Complications in Breast Reduction Surgery: A Retrospective Association Study

Abstract Background The impact of antidepressant use on surgical outcomes remains uncertain, particularly in breast reduction surgery, where risks of infection, wound complications, and bleeding may influence decision-making. Objectives To evaluate the association between preoperative antidepressant use and postoperative complications following breast reduction surgery. Methods We performed a retrospective multicenter cohort study using the TriNetX Research Network. Adults undergoing bilateral breast reduction between 2010 and 2025 were stratified by recent antidepressant exposure. Propensity score matching balanced demographics, comorbidities, and laboratory values. Outcomes within 90 days included surgical-site infection, wound dehiscence, hematoma, seroma, sepsis, thromboembolism, composite complications, readmission, emergency-room visit, and opioid prescriptions. Results After matching, 7,411 patients with antidepressant use were compared with 7,411 controls. Antidepressant exposure was associated with increased risks of infection (5.1% vs 4.1%; p=0.006), wound dehiscence (4.1% vs 2.8%; p < 0.001), and sepsis (0.4% vs 0.2%; p=0.031). Hematoma/seroma rates did not differ. Opioid prescribing was higher in antidepressant users (29.1% vs 23.8%; p < 0.001). Class specific analyses indicated that selective serotonin reuptake inhibitors carried a slightly higher risk than serotonin norepinephrine reuptake inhibitors. Patients with prescriptions for two or more antidepressants had higher rates of infection and overall complications than those on a single agent. Conclusions Preoperative antidepressant exposure was associated with modest increases in infection, wound dehiscence, sepsis, and postoperative opioid prescribing after breast reduction surgery, while bleeding complications were not increased. These observational findings are hypothesis-generating and warrant further validation.