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Perioperative Selective Serotonin Reuptake Inhibitor (SSRI) Use and Postoperative Fracture Fixation Outcomes: A Multi-institutional Retrospective Cohort Study
Journal article   Open access   Peer reviewed

Perioperative Selective Serotonin Reuptake Inhibitor (SSRI) Use and Postoperative Fracture Fixation Outcomes: A Multi-institutional Retrospective Cohort Study

Anish Ponna, Shreyas Soma, Zachary J Demetriou, Alec Giakas and Asif Ilyas
Curēus (Palo Alto, CA), v 18(8), e114976
22 Aug 2026
DOI: https://doi.org/10.7759/cureus.114976
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https://doi.org/10.7759/cureus.114976View
Published, Version of Record (VoR) Open

Abstract

Introduction: Selective serotonin reuptake inhibitors (SSRIs) have been implicated in impaired bone metabolism and delayed fracture healing. This study evaluates the association between perioperative SSRI use and complications following open reduction and internal fixation (ORIF) and intramedullary nailing (IMN) of various long bone shaft fractures. The study hypothesis is that perioperative SSRI use negatively affects fracture healing and increases adverse postoperative outcomes across fixation constructs. Methods: The TriNetX database was used to identify patients (≥18 years) undergoing humeral, clavicular, or ulna shaft ORIF and humeral, femoral, or tibial shaft IMN. Patients were stratified by SSRI use within one month of the index surgery; controls had no documented SSRI history. Propensity score matching controlled for demographics and relevant comorbidities. Outcomes were assessed at one-year after surgery. Measures of association, including risk ratios (RRs), 95% confidence intervals (CIs), and p-values, were used to compare outcomes between cohorts. Results: In the humeral shaft ORIF cohort (n=1,576), SSRI exposure was associated with significantly higher rates of nonunion (RR=1.51, 95% CI: 1.14-2.01; p=0.004) and infection-related implant failure (RR=2.03, 95% CI: 1.31-3.16; p=0.001). In the ulna shaft ORIF cohort (n=567), SSRI use was associated with increased infection-related implant failure (RR=1.94, 95% CI: 1.12-3.39; p=0.017) and mechanical implant failure (RR=1.91, 95% CI: 1.14-3.19; p=0.012). No significant associations were identified in the clavicle shaft ORIF cohort or in any IMN cohort (p>0.05). Conclusion: The study hypothesis was not upheld. While significant adverse associations were observed in select ORIF cohorts, there were no significant differences in adverse outcomes in IMN cohorts. This discrepancy limits the ability to draw an association between SSRI use and impaired fracture healing. Given the higher baseline nonunion rates associated with IMN, the observed differences between cohorts appear inconsistent and likely reflect confounding rather than a true effect of SSRI use.

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