Nagamine T. Beyond analgesia: A comprehensive opinion review on the dual-action strategy of celecoxib and duloxetine in knee osteoarthritis. World J Psychiatry 2026; 16(8): 116224 [DOI: 10.5498/wjp.116224]
Corresponding Author of This Article
Takahiko Nagamine, MD, PhD, Department of Psychiatric Internal Medicine, Sunlight Brain Research Center, 4-13-18 Jiyugaoka, Hofu 7470066, Yamaguchi, Japan. tnagamine@outlook.com
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Psychiatry
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Nagamine T. Beyond analgesia: A comprehensive opinion review on the dual-action strategy of celecoxib and duloxetine in knee osteoarthritis. World J Psychiatry 2026; 16(8): 116224 [DOI: 10.5498/wjp.116224]
World J Psychiatry. Aug 19, 2026; 16(8): 116224 Published online Aug 19, 2026. doi: 10.5498/wjp.116224
Beyond analgesia: A comprehensive opinion review on the dual-action strategy of celecoxib and duloxetine in knee osteoarthritis
Takahiko Nagamine
Takahiko Nagamine, Department of Psychiatric Internal Medicine, Sunlight Brain Research Center, Hofu 7470066, Yamaguchi, Japan
Author contributions: All aspects of this work were carried out by the sole author, Nagamine T.
Conflict-of-interest statement: The author reports no relevant conflicts of interest for this article.
Corresponding author: Takahiko Nagamine, MD, PhD, Department of Psychiatric Internal Medicine, Sunlight Brain Research Center, 4-13-18 Jiyugaoka, Hofu 7470066, Yamaguchi, Japan. tnagamine@outlook.com
Received: November 6, 2025 Revised: December 20, 2025 Accepted: February 5, 2026 Published online: August 19, 2026 Processing time: 258 Days and 3.8 Hours
Abstract
Knee osteoarthritis is no longer viewed solely as a peripheral joint disease but as a complex biopsychosocial condition involving central sensitization and psychological distress. Recently, the combination of celecoxib (a cyclooxygenase-2 inhibitor) and duloxetine (a serotonin-norepinephrine reuptake inhibitor) has gained traction for addressing this “pain-depression-anxiety” triad. This opinion review evaluates the synergistic efficacy and antagonistic risks of dual-action therapy. We aim to move beyond short-term retrospective data to provide a long-term pharmacovigilance perspective. The combination offers superior analgesia and “opioid-sparing” potential by targeting both peripheral inflammation and descending inhibitory pathways. However, this synergy of efficacy is matched by a “synergy of toxicity”. Risks include exacerbated hypertension, increased gastrointestinal bleeding due to serotonin-platelet interactions, and a “fall-risk paradox” where drug-induced dizziness offsets the functional gains of pain relief. While promising for the “centralized-distressed” knee osteoarthritis phenotype, this regimen requires rigorous patient screening and a pre-defined exit strategy. Clinicians must balance the promise of psychological restoration against the formidable physiological risks of the aging patient.
Core Tip: Combining celecoxib and duloxetine is more effective than celecoxib alone for pain, depression, and anxiety in patients with knee osteoarthritis. However, its assertion of safety after only eight weeks is overly optimistic. Prescribers must be warned about the serious long-term risks that were not adequately covered. Celecoxib carries established cardiovascular and gastrointestinal risks, while duloxetine poses significant risks for hepatotoxicity, central nervous system side effects (like dizziness and falls), and a severe discontinuation syndrome. Given that typical knee osteoarthritis patients are often older and present with comorbidies, the combination requires thorough cardiovascular and hepatic screening, meticulous review for drug-drug interactions, and informed consent regarding the mandatory slow tapering of duloxetine. The evidence is preliminary; this dual-action treatment should be reserved for patients who have failed simpler strategies.
