A Double-blind, Randomized, Placebo-controlled Study of the Efficacy and Safety of Duloxetine for the Treatment of Chronic Pain Due to Osteoarthritis of the Knee


  • Disclosure: This study was sponsored by Eli Lilly and Company, Indianapolis, IN, USA. Drs Chappell, Skljarevski, Desaiah, Liu-Seifert, and Ms. Zhang are employees and stockholders of Eli Lilly and Company. Drs Belenkov and Brown were participating investigators in the conduct of this study and received funding from Eli Lilly and Company.

Durisala Desaiah, PhD, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, U.S.A. E-mail: desaiahdu@lilly.com.


Objective:  To evaluate the efficacy and safety of duloxetine in the treatment of chronic pain due to osteoarthritis of the knee.

Methods:  This was a 13-week, randomized, double-blind, placebo-controlled trial in patients meeting American College of Rheumatology clinical and radiographic criteria for osteoarthritis of the knee. At baseline, patients were required to have a ≥ 4 weekly mean of the 24-hour average pain ratings. Patients were randomized to either duloxetine 60 mg once daily (QD) or placebo. At week 7, the duloxetine dosage was increased, in a blinded fashion, to 120-mg QD in patients reporting < 30% pain reduction. The primary efficacy measure was Brief Pain Inventory (BPI) 24-hour average pain. Secondary efficacy measures included Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); Clinical Global Impressions of Severity (CGI-S). Safety and tolerability was also assessed.

Results:  Of the total (n = 256) patients, 111 (86.7%) in placebo group and 93 (72.7%) in duloxetine group completed the study. Patients treated with duloxetine had significantly (P ≤ 0.001) greater improvement at all time points on BPI average pain and had significantly greater improvement on BPI pain severity ratings (P ≤ 0.05), WOMAC total (P = 0.044) and physical functioning scores (P = 0.016), and CGI-S (P = 0.009) at the study endpoint. Frequency of treatment-emergent nausea, constipation, and hyperhidrosis were significantly higher in the duloxetine group (P ≤ 0.05). Significantly more duloxetine-treated patients discontinued the trial because of adverse events (P = 0.002).

Conclusions:  Treatment with duloxetine 60 mg to 120 mg QD was associated with significant pain reduction and improved function in patients with pain due to osteoarthritis of the knee.