en روماتولوژی Rheumatology پژوهشی Research Article <div style="text-align: justify;"><span style="font-size:14px;"><span style="font-family:Tahoma;"><span style="line-height:2;"><strong>Background</strong>: Osteoarthritis (OA) is a degenerative joint disorder causing pain and disability. The present treatments are inadequate to improve the underlying pathogenesis of OA. Melatonin, because of its chondroprotective, anti-inflammatory, and antioxidant properties, may have a role in the management of OA. Duloxetine is presumed to modulate pain through serotonergic and noradrenergic pathways. In the present study, as a first study, melatonin has been compared with duloxetine for its efficacy in reducing OA-related knee pain.<br> <strong>Methods</strong>: This randomized controlled trial (RCT) study involved 60 knee OA patients treated at Imam Hossein Hospital in Tehran, Iran. Participants were randomly assigned to receive either melatonin, 3-10 mg per day, or duloxetine, 60-120 mg per day. The primary outcome measure was the 3-month change in the Western Ontario and McMaster universities OA index (WOMAC) score.<br> <strong>Results</strong>: Compared to the duloxetine group, a reduction in the total WOMAC score was noted in the melatonin group (P=0.001 and P=0.09, respectively). Changes in WOMAC pain score were significant in both groups (P=0.0001). Additionally, the need for naproxen for breakthrough pain was significantly lower in the melatonin group (318.33&plusmn;16 mg vs 810&plusmn;35 mg with a P<0.001).<br> <strong>Conclusion</strong>: Melatonin is more potent than duloxetine in pain reduction and functional improvement in patients with knee OA. Considering the ability of melatonin to reduce the usage of nonsteroidal anti-inflammatory drugs, melatonin may be a safer agent for managing pain in OA.&nbsp;</span></span></span></div> Osteoarthritis (OA), Melatonin, Duloxetine, Western Ontario and McMaster universities osteoarthritis index (WOMAC) 43 48 http://jros.iums.ac.ir/browse.php?a_code=A-10-1597-1&slc_lang=en&sid=1 Parisa Delkash parisa.delkash@yahoo.com 10031947532846007105 10031947532846007105 No Clinical Research Development Unit, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Minoo Heidari Almasi minoheidari.mh@gmail.com 10031947532846007106 10031947532846007106 No Clinical Research Development Unit, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Hamideh Moradi Shahrbabak hamidehmoradi05@gmail.com 10031947532846007107 10031947532846007107 No Clinical Research Development Unit, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Shideh Ariana shideh.ryn23@yahoo.com 10031947532846007108 10031947532846007108 No Perinatology Division, Department of Obstetrics and Gynecology, School of Medicine, Imam Hossein Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Roya Vaziri-Harami roya832003@yahoo.com 10031947532846007109 10031947532846007109 Yes Clinical Research Development Unit, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.