Selective serotonin reuptake inhibitors may reduce risk of total joint arthroplasty in osteoarthritis

1. Initiation of centrally acting analgesics in patients with osteoarthritis (OA) was associated with a higher long-term risk of total joint arthroplasty compared with SSRI initiation.

2. Management of comorbid depression may play an important role in OA symptom progression and surgical outcomes, potentially exceeding the benefit of centrally mediated analgesic effects alone.

Evidence Rating Level: 3 (Average)

This population-based cohort study evaluated whether centrally acting analgesics (CAAs), including tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, and gabapentinoids, were associated with reduced progression of osteoarthritis (OA) compared with selective serotonin reuptake inhibitors (SSRIs). Using the UK IQVIA Medical Research Database, investigators conducted a propensity score–matched, new-user, active-comparator cohort study of adults aged 40–89 years with knee or hip OA between 2000 and 2021. A total of 11,734 incident CAA users were matched 1:1 with 11,734 SSRI initiators and followed for development of total joint arthroplasty (TJA), a surrogate marker of advanced OA progression. Median follow-up was approximately 9 years. Contrary to the study hypothesis, CAA initiation was associated with a significantly increased risk of TJA compared with SSRI initiation (HR 1.81, 95% CI 1.59–2.07). The association persisted after adjustment for confounders, competing risk of death, and treatment discontinuation (adjusted HR 1.48, 95% CI 1.22–1.80). Similar findings were observed in analyses of tricyclic antidepressants and gabapentinoids individually. In patients with both OA and depression, the association was attenuated and no longer statistically significant after full adjustment. The findings suggest that SSRIs, potentially through improved management of comorbid depression, may confer benefits on OA outcomes beyond direct analgesic mechanisms.

Click here to read the study in BMC Medicine

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