Impact of Antidepressant Use on Complications Following Ankle Fracture Management: A Multi-institutional Propensity-Matched Cohort Analysis

Background: This study evaluated the relationship between antidepressant prescription (ADP) and postoperative complications in patients undergoing ankle open reduction internal fixation (ORIF). Methods: A retrospective cohort study that uses multi-institutional data from the Trinetx research platform identified patients who underwent ankle ORIF on or before December 10, 2024, with at least 2 ADP doses and 2 years of follow-up using Current Procedural Terminology ( CPT ) and International Classification of Diseases, Tenth Revision ( ICD-10 ) codes. Outcomes were grouped into 90-day systemic and 2-year mechanical complication families. The false discovery rate was controlled at 5% using the Benjamini-Hochberg procedure, and results are reported as risk ratios with 95% CIs. Results: Of 70 813 patients, 13 610 (19.2%) used antidepressants. After matching (11.071 per group), antidepressant use was associated with significantly higher rates of short-term complications, including infection, wound disruption, and hospital readmission. At 2-year follow-up, use of antidepressants was significantly associated with increased rates of mechanical complications, including higher rates of hardware failure, osteoarthritis, removal, nonunion, and amputation. The outcomes remained significant after multiple-testing adjustment. Conclusion: Preoperative antidepressant prescription was associated with increased postoperative and long-term complications after ankle ORIF. These observational findings support tailored perioperative management and monitoring, particularly for patients with preoperative antidepressant prescriptions.