Antidepressant Use and Risk of Reoperation After Distal Radius Open Reduction and Internal Fixation: A Propensity Score-Matched Cohort Study.

PURPOSE: Antidepressant use is common and has been linked to impaired bone remodeling, but its effect on fracture healing after fixation remains unclear. The purpose of this study was to examine whether selective serotonin reuptake inhibitors (SSRIs) and, separately, agents that modulate serotonergic signaling but are not SSRIs (non-SSRI serotonergic antidepressants) were associated with unplanned return to the operating room (RTOR) after open reduction and internal fixation (ORIF) of distal radius fractures.

METHODS

We performed a retrospective, propensity score-matched cohort study using TriNetX, a global federated research network that aggregates deidentified electronic health record data from large health care organizations. Adults who underwent surgery within 14 days of distal radius fracture diagnosis were included and the ORIF date served as the index. Two mutually exclusive exposure comparisons were analyzed: SSRI users versus nonusers and non-SSRI serotonergic users (serotonin-norepinephrine reuptake inhibitors), tricyclic antidepressants, serotonergic monoamine oxidase inhibitors, vortioxetine, or vilazodone versus nonusers, defined by ≥2 prescriptions in the 180 days preindex. Cohorts were balanced using 1:1 greedy nearest-neighbor propensity-score matching (caliper 0.10). The primary outcome was unplanned RTOR 30-365 days postindex, defined as nonunion repair or repeat fixation. We estimated absolute risk differences, risk ratios (RRs), and Cox hazard ratios (HRs) with 95% confidence intervals (CIs).

RESULTS

After matching, 2,657 SSRI users and 2,197 non-SSRI serotonergic users were compared with equal numbers of nonusers. Unplanned RTOR occurred in 47 (1.8%) SSRI users versus 20 (0.8%) nonusers (ARD 1.0%, RR 2.35, HR 2.25; 95% CI 1.33-3.79). Non-SSRI serotonergic users had 52 events (2.4%) versus 14 (0.6%) in nonusers (ARD 1.7%, RR 3.71, HR 3.62; 95% CI 2.01-6.54). Findings were consistent across absolute risk comparisons and time-to-event analyses.

CONCLUSIONS

Preoperative antidepressant exposure to SSRIs or non-SSRI serotonergic agents was associated with a small but clinically relevant increase in unplanned reoperation after distal radius ORIF.

TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic III.