pain is the leading symptom of osteoarthritis (OA) and is often chronic in nature, leading to significant morbidity and decreased quality of life. Duloxetine, a selective serotonin norepinephrine reuptake inhibitor has been demonstrated to have a centrally acting analgesic effect. the aim of the present study was to investigate the efficacy of duloxetine in reducing pain in older adults with knee OA. totally, 288 patients aged 65 years and above with primary knee OA were enrolled in this study. Patients were randomised 1:1. Totally, 144 received 60 mg/day of duloxetine HCL and 144 received placebo for 16 weeks. Outcome measures included pain reduction and improvement in physical functioning scores. Pain was assessed using the visual analogue pain scale (VAS; 0-100 mm). The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were used to assess function. two-hundred and seventy four of the 288 patients completed the study. There was a statistically significant reduction in pain and a significant improvement in WOMAC scores at 16 weeks in the duloxetine group versus the placebo group. No serious side effects were reported. the findings of the present study provide evidence for the efficacy and tolerability of duloxetine in reducing pain and subsequently improving function in older adults with knee OA. NCT01425827.