What is the recommended dosing for duloxetine (Cymbalta) for osteoarthritis?

From the Guidelines

The recommended dosing for duloxetine (Cymbalta) for osteoarthritis is 60 mg once daily, with treatment typically beginning at 30 mg daily for one week before increasing to the target dose to improve tolerability. This recommendation is based on the most recent and highest quality study, which suggests that duloxetine is effective in reducing chronic pain associated with osteoarthritis 1.

Key Considerations

• Duloxetine should be taken at the same time each day, with or without food, and the capsule should be swallowed whole without crushing or chewing.
• The medication works by inhibiting the reuptake of serotonin and norepinephrine in the central nervous system, which helps modulate pain signals and can reduce chronic pain associated with osteoarthritis.
• Patients should be aware that it may take several weeks to experience the full benefit of duloxetine for pain relief.
• Common side effects include nausea, dry mouth, constipation, fatigue, and dizziness, which often improve over time.
• Duloxetine should not be stopped abruptly but rather tapered gradually to avoid discontinuation symptoms, as recommended by the 2020 VA/DoD Clinical Practice Guideline for the Non-Surgical Management of Hip & Knee Osteoarthritis 1.

Special Populations

• Patients with severe renal impairment (creatinine clearance <30 mL/min) or hepatic insufficiency should use lower doses or avoid the medication altogether, as suggested by the evidence 1.
• The use of duloxetine in older adults (>65 years) and in patients with knee osteoarthritis may be more effective, as noted in the CDC Clinical Practice Guideline for Prescribing Opioids for Pain - United States, 2022 1.

Evidence Summary

The evidence from the 2020 VA/DoD Clinical Practice Guideline for the Non-Surgical Management of Hip & Knee Osteoarthritis 1 and the CDC Clinical Practice Guideline for Prescribing Opioids for Pain - United States, 2022 1 supports the use of duloxetine for osteoarthritis, with a recommended dosing of 60 mg once daily. The American College of Rheumatology/Arthritis Foundation guideline for the management of osteoarthritis of the hand, hip, and knee also conditionally recommends duloxetine for patients with knee, hip, and/or hand OA 1.

From the FDA Drug Label

The recommended duloxetine delayed-release capsules dosage is 60 mg once daily in adults with chronic musculoskeletal pain, which includes osteoarthritis. Begin treatment at 30 mg once daily for one week, to allow patients to adjust to duloxetine delayed-release capsules before increasing to 60 mg once daily

The recommended dosing for duloxetine (Cymbalta) for osteoarthritis is 60 mg once daily, starting with 30 mg once daily for one week.

• The dose can be increased to 60 mg once daily after one week.
• There is no evidence that higher dosages confer additional benefit, even in patients who do not respond to a 60 mg once daily dosage, and higher dosages are associated with a higher rate of adverse reactions 2.

From the Research

Dosing for Duloxetine in Osteoarthritis

• The recommended dosing for duloxetine (Cymbalta) in the treatment of osteoarthritis is 60 mg once-daily, as indicated in studies 3, 4, 5.
• This dosing has been shown to be effective in managing chronic musculoskeletal pain due to chronic osteoarthritis pain and chronic low back pain 3.
• A post hoc analysis of two randomized, placebo-controlled trials found that duloxetine 60 mg/day was efficacious and generally well tolerated for the management of symptomatic knee OA in both older and younger patients 4.
• Another study found that duloxetine was superior to placebo on the primary efficacy measure of weekly mean 24-h pain scores, beginning at Week 1 and continuing through the treatment period 5.

Alternative Dosing

• Some studies have explored the efficacy of increasing the dose to 120 mg in non-responding patients, but this has not been found to provide additional benefit 4, 6.
• A systematic review of duloxetine for osteoarthritic pain found that the number needed to treat (NNT) for pain relief was 7, and the number needed to harm (NNH) for relevant dichotomous adverse outcomes was 16-19 6.

Safety and Efficacy

• Duloxetine has been found to be generally well tolerated, with common adverse reactions including nausea, fatigue, and constipation 4, 5, 6.
• The likelihood to be helped or harmed (LHH) has been found to be consistently greater than 1, indicating that duloxetine is efficacious and tolerable for the treatment of chronic pain associated with OA 6.