Fluoxetine and Paroxetine Exhibit a Protective Effect Against Total Joint Arthroplasty in Patients With Osteoarthritis.

Background Recent research has elucidated the biochemical mechanism by which some selective serotonin reuptake inhibitor (SSRI) drugs, fluoxetine and paroxetine, slow osteoarthritis (OA) disease progression. This novel study aimed to evaluate the impact of fluoxetine and paroxetine on the risk of undergoing primary total hip (THA) or knee arthroplasty (TKA) among OA patients.  Methods A retrospective cohort study using the TriNetX network compared OA patients prescribed fluoxetine (n=2478) or paroxetine (n=1500) to matched controls without SSRI exposure. Outcomes were assessed via risk analysis, Kaplan-Meier survival analysis, and hazard ratios (HR).  Results The absolute risk of needing THA or TKA was significantly lower in both SSRI cohorts compared to matched controls. In the fluoxetine cohort, the relative risk (RR) of undergoing THA or TKA was 0.678 (95% CI: 0.645-0.713), while in the paroxetine cohort, it was 0.791 (95% CI: 0.740-0.845). The fluoxetine cohort had an 8.22% chance of requiring total joint arthroplasty (TJA), compared to 14.15% in controls. The paroxetine cohort had an 8.14% chance versus 8.46% in controls. This corresponds to a 1.1% absolute reduction in risk for fluoxetine (95% CI: 1.0-1.3%, p<0.0001) and a 0.7% reduction for paroxetine (95% CI: 0.5-0.9%, p<0.0001). The fluoxetine cohort had a hazard ratio (HR) of 0.675 (95% CI: 0.642-0.711, p<0.0001), while the paroxetine cohort had an HR of 0.742 (95% CI: 0.694-0.794, p<0.0001). Conclusion Patients prescribed either paroxetine or fluoxetine had a statistically significant decrease in risk of undergoing THA or TKA; however, further research is needed to explore other clinical outcomes and therapeutic benefits of SSRIs in OA management.