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Non-steroidal anti-inflammatory drugs (NSAIDs) are at the cornerstone of treatment for osteoarthritis (OA). In recent years, the widespread use of oral NSAIDs has been called into question due to the appearance of significant upper gastrointestinal (GI) complications and cardiovascular (CV) adverse events (AEs). However, NSAIDs are non-homogeneous, and there are noticeable differences between them in AE risk for GI and CV events. Nevertheless, if properly prescribed oral NSAIDs can provide an effective and safe treatment for OA in real-life situations. The identification of patients with significant CV and/or GI risk is critical, and the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) treatment algorithm provides guidance on appropriate treatments for OA patients with elevated risk. Among non-selective NSAIDs, ibuprofen and naproxen seem preferable to diclofenac, the latter being associated with higher CV risk. Recommendation has been made by some that naproxen may be the preferred agent in patients at high CV risk because of its lower risk of CV events. Low dose celecoxib (200mg/day) is also associated with a lower risk of CV events compared with other coxibs. In addition, drugs with a demonstrated low GI risk profile may be of benefit, such as coxibs and nabumetone. Among patients who fail to respond adequately to sequential ESCEO algorithm Step 1 and Step 2 treatments, the short-term use of weak opioids, such as tramadol, for severely symptomatic OA patients is recommended. Although studies exploring the efficacy of tramadol in OA are limited, there is good evidence that tramadol works if prescribed properly. The sustained-release (SR) formulation of tramadol is preferred as it avoids the peak plasma concentrations reached with immediate-release tramadol, and is believed to reduce the incidence of AEs. Furthermore, slow upwards titration of tramadol SR is recommended to improve tolerability and minimize treatment discontinuations.

Original publication




Journal article


Semin arthritis rheum

Publication Date





S22 - S27


Analgesics, Coxibs, Cyclo-oxygenase-2 (COX-2) inhibitors, Knee osteoarthritis, Oral non-steroidal anti-inflammatory drugs (NSAIDs), Tramadol, Analgesics, Anti-Inflammatory Agents, Non-Steroidal, Cardiovascular Diseases, Evidence-Based Medicine, Gastrointestinal Diseases, Humans, Osteoarthritis, Randomized Controlled Trials as Topic, Risk Factors