No Added Value of Duloxetine in Patients With Chronic Pain due to Hip or Knee Osteoarthritis: A Cluster-Randomized Trial

Abstract

Objective: To assess the effectiveness of duloxetine in addition to usual care in patients with chronic osteoarthritis (OA) pain. The cost-effectiveness and whether the presence of symptoms of centralized pain alters the response to duloxetine were secondary objectives.

Methods: We conducted an open-label, cluster-randomized trial. Patients with chronic hip or knee OA pain who had an insufficient response to acetaminophen and nonsteroidal antiinflammatory drugs were included. Randomization took place at the general practice level, and patients received duloxetine (60 mg/day) in addition to usual care or usual care alone. The presence of centralized pain was defined as a modified PainDETECT Questionnaire score >12. The primary outcome measure was Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores (scale 0-20) at 3 months after the initiation of treatment. Our aim was to detect a difference between the groups of a clinically relevant effect of 1.9 points (effect size 0.4). We used a linear mixed model with repeated measurements to analyze the data.

Results: In total, 133 patients were included, and 132 patients were randomized into treatment groups. A total of 66 patients (at 31 practices) were randomized to receive duloxetine in addition to usual care, and 66 patients (at 35 practices) were randomized to receive usual care alone. We found no differences in WOMAC pain scores between the groups at 3 months (adjusted difference -0.58 [95% confidence interval (95% CI) -1.80, 0.63]) or at 12 months (adjusted difference -0.26 [95% CI -1.86, 1.34]). In the subgroup of patients with centralized pain symptoms, we also found no effect of duloxetine compared to usual care alone (adjusted difference -0.32 [95% CI -2.32, 1.67]).

Conclusion: We found no effect of duloxetine added to usual care compared to usual care alone in patients with chronic knee or hip OA pain. Another trial including patients with centralized pain symptoms should be conducted to validate our results.

Figure 1

Flow chart of the study design showing that general practitioners were invited to participate and either declined or accepted. General practice records of patients with knee or hip OA were reviewed for exclusion criteria, and included patients were randomized to receive either duloxetine in addition to usual care or usual care alone.

Figure 2

Course of WOMAC scores for for pain (A) and function (B) over time in OA patients receiving duloxetine in addition to usual care compared to those receiving usual care alone. Results are the mean ± SD, in which circles represent the mean for the indicated group and bars represent the SD.

Figure 3

Number of patients with chronic hip or knee osteoarthritis pain who were receiving treatment with duloxetine at baseline (BL) and at months 3, 6, 9, and 12 of follow‐up.