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Background <p>Centrally acting analgesics (CAAs) are first-line therapy for neuropathic pain, while selective serotonin reuptake inhibitors (SSRIs) are first-line agents for managing depression, but their effects on osteoarthritis (OA) are unclear. We aimed to evaluate the relation of CAA versus SSRI use to risk of total joint arthroplasty (TJA) among people with OA in a population-based cohort.</p> Methods <p>We conducted a propensity score-matched, new-user design, active comparator, population-based cohort study using data from IQVIA Medical Record Database (IMRD), limited to people with OA aged between 40 and 89. We identified incident CAA and SSRI users and propensity-score matched them 1:1 using one-year cohort accrual blocks. We compared the risk of TJA among CAA initiators to SSRI initiators using Cox proportional hazards regression. We conducted subgroup analyses limited to those with both OA and depression. We repeated analyses accounting for the competing risk of death using a Fine-Gray model.</p> Results <p>CAA initiators (<i>n</i> = 11,734) had a higher risk of knee/hip arthroplasty compared with SSRI initiators (<i>n</i> = 11,734), with the propensity score–matched hazard ratio (HR) of 1.81 (95% CI 1.59, 2.07). When additionally adjusted for confounders and when accounting for competing risk of death and drug discontinuation, the effect estimate was slightly reduced (HR 1.48; 95% CI 1.22, 1.80). Subgroup analysis limited to those with both OA and depression demonstrated a positive but non-significant effect estimate.</p> Conclusions <p>CAA initiation was associated with higher risk of TJA compared with SSRI initiation. These results may suggest that agents that predominantly impact depression may also have beneficial effects on knee OA progression.</p>

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Associations of centrally acting analgesic use with total joint arthroplasty compared to selective serotonin reuptake inhibitor among osteoarthritis patients in a large prospective cohort

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月13日

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  • Zhiqiang Wang,
  • Maggie Westerland,
  • Christine Peloquin,
  • Michael LaValley,
  • Eva Petrow,
  • Margaret Clancy,
  • Wei Hu,
  • Changhai Ding,
  • Tuhina Neogi

摘要

Background

Centrally acting analgesics (CAAs) are first-line therapy for neuropathic pain, while selective serotonin reuptake inhibitors (SSRIs) are first-line agents for managing depression, but their effects on osteoarthritis (OA) are unclear. We aimed to evaluate the relation of CAA versus SSRI use to risk of total joint arthroplasty (TJA) among people with OA in a population-based cohort.

Methods

We conducted a propensity score-matched, new-user design, active comparator, population-based cohort study using data from IQVIA Medical Record Database (IMRD), limited to people with OA aged between 40 and 89. We identified incident CAA and SSRI users and propensity-score matched them 1:1 using one-year cohort accrual blocks. We compared the risk of TJA among CAA initiators to SSRI initiators using Cox proportional hazards regression. We conducted subgroup analyses limited to those with both OA and depression. We repeated analyses accounting for the competing risk of death using a Fine-Gray model.

Results

CAA initiators (n = 11,734) had a higher risk of knee/hip arthroplasty compared with SSRI initiators (n = 11,734), with the propensity score–matched hazard ratio (HR) of 1.81 (95% CI 1.59, 2.07). When additionally adjusted for confounders and when accounting for competing risk of death and drug discontinuation, the effect estimate was slightly reduced (HR 1.48; 95% CI 1.22, 1.80). Subgroup analysis limited to those with both OA and depression demonstrated a positive but non-significant effect estimate.

Conclusions

CAA initiation was associated with higher risk of TJA compared with SSRI initiation. These results may suggest that agents that predominantly impact depression may also have beneficial effects on knee OA progression.