Duloxetine Does Not Improve Pain in Patients With Knee Osteoarthritis

While investigators were hopeful that duloxetine, an SNRI, would reduce chronic pain in patients with knee osteoarthritis, results were lackluster and clinically insignificant.

Concomitant duloxetine, a serotonin and norepinephrine reuptake inhibitor (SNRI), did not have added benefits for patients with chronic osteoarthritis (OA), according to a study published in Arthritis & Rheumatology.1

“OA is one of the major chronic pain conditions of the musculoskeletal system and approximately 15% of the population suffers from OA. Persistent pain and loss of function are two important complaints of patients with OA,” investigators explained. “Duloxetine is hypothesized to reduce chronic pain by central inhibition of pain and acts by modulation of descending (inhibitory) pain pathways in the central nervous system.”

In this open-label, cluster randomized trial, investigators enrolled patients from general practices who had OA and were experiencing chronic hip or knee pain with an insufficient response or adverse reactions to paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs). Patients were randomized to either receive duloxetine 60 mg/day or continue with usual care alone. Patients were started at a 30 mg/day dose to minimize adverse events. Effects were analyzed at 2 weeks, and then 1, 3, 6, 9, and 12 months. Usual care included diet, physiotherapy, analgesics, lifestyle advice, and education.

Patients completed questionnaires at week 6 and then at 3, 6, 9, and 12 months. Patient-reported adverse events and co-interventions were reported. Satisfaction of treatment was measured on a scale of 0 to 10 and improvement was evaluated via a 7-point Likertscale.

Primary outcome was the Western Ontario Mc Master Universities (WOMAC) Osteoarthritis Index for pain (0-20) at the 3-month mark. The goal was to identify a difference between groups of a clinically significant effect of 1.9. A painDETECT score of >12, the secondary outcome, was used to categorize centralized pain.

A linear mixed model evaluated the data.

A total of 132 patients, 66 receiving duloxetine and 66 receiving usual care, were included in the study. The 12-month follow-up was completed by 80.3% of patients (53 in each cohort). The duloxetine cohort had fewer women when compared with the control group (59.1% vs 75.8%, respectively), were younger (63.2 years vs 65.4 years, respectively), and had fewer comorbidities (15.2% vs 33.2% with 2 or more comorbidities, respectively). Participants with centralized pain (40%) had higher WOMAC pain scores.

No significant differences were detected between the groups for WOMAC pain at 3 months (adjusted difference -0.58 95% CI) or at 12 months (adjusted difference -0.26 95% CI. Analyses were adjusted for comorbidities, age, sex, depression scores, and a modified painDETECT score.

The duloxetine subgroup reported no effect on symptoms or pain with the inclusion of the drug (-0.32 95% CI). Quality of life and patient satisfaction showed small, clinically insignificant differences between both cohorts.

For those chosen to receive duloxetine, 15% opted to not begin duloxetine for fear of adverse events. By the 3-month follow-up, 61% of patients were still being treated with the drug, which further reduced to 35% at 1 year. Reasons for discontinuing the medication included side effects (49%), no effect (24%), or a combination of side effects and no effect (18%). At 3 months, 75.2% of patients in the usual care cohort reported 1 or more adverse events, compared with 89.3% of those in the duloxetine cohort. Common side effects included nausea, constipation, hyperhidrosis, weight loss, and yawning for those receiving the drug. Additionally, the duloxetine group contacted their physician significantly more than those receiving usual care treatment (51.8% vs 30.8%, respectively).

The study was strengthened by its cluster design, which allowed for evaluating implementation of the drug in a “real-life” setting. Unfortunately, investigators were unable to recruit the number of patients they initially desired. However, results were still deemed clinically relevant.

“There was no clinically relevant effect of duloxetine added to usual care compared to usual care alone for chronic OA pain and it should not be implemented,” investigators concluded. “For patients with symptoms of centralized pain an effect cannot be ruled out and future research in this subgroup is needed to confirm our results.”


van den Driest JJ, Schiphof D, Koffeman AR, Koopmanschap MA, Bindels PJE, Bierma-Zeinstra SMA. No added value of duloxetine for patients with chronic pain due to hip or knee osteoarthritis: a cluster randomised trial [published online ahead of print, 2022 Jan 6]. Arthritis Rheumatol. 2022;10.1002/art.42040. doi:10.1002/art.42040