CAA Use Tied to Higher Arthroplasty Risk

In a UK cohort, patients with osteoarthritis who initiated centrally acting analgesics had a higher hazard of knee or hip replacement than those who initiated SSRIs, though residual confounding by pain severity remains a key limitation.

By
Andrea Surnit
June 1, 2026
6 min

Conexiant

Overview

A population-based cohort study found that patients with knee or hip osteoarthritis who initiated centrally acting analgesics (CAA) had a significantly higher risk of total joint arthroplasty compared to those who initiated selective serotonin reuptake inhibitors (SSRIs).

Background

The management of knee and hip osteoarthritis is critical as it significantly impacts patient quality of life and may lead to surgical interventions such as joint replacement. Understanding the implications of different analgesic treatments on the progression of osteoarthritis is essential.

Data Highlights

Group	Patients	Joint Replacement Events	Hazard Ratio (HR)
Centrally Acting Analgesics	11,734	617 (5.3%)	1.81 (95% CI 1.59–2.07)
SSRIs	11,734	327 (2.8%)	1.00

Key Findings

Centrally acting analgesic initiation was associated with an 81% higher hazard of knee or hip replacement compared to SSRIs.
Over a median follow-up of 9.5 years, 5.3% of patients on CAAs underwent joint replacement versus 2.8% on SSRIs.
In a subgroup with both osteoarthritis and depression, the hazard was 59% higher for CAA initiation.
Tricyclic antidepressants and gabapentinoids were associated with a 34% and 50% higher hazard of joint replacement, respectively.

Clinical Implications

Clinicians should be aware of the increased risk of joint replacement associated with the use of centrally acting analgesics in patients with osteoarthritis.

Conclusion

The study's findings suggest that centrally acting analgesics do not provide a protective effect against joint replacement in osteoarthritis patients.