What is the role of duloxetine (Cymbalta) in the management of arthritis or chronic musculoskeletal (MSK) pain?

From the Guidelines

Duloxetine is a recommended option for managing chronic musculoskeletal pain, including osteoarthritis pain, due to its effectiveness in reducing pain intensity and improving function, as shown in recent studies 1.

Key Points to Consider

• The typical starting dose of duloxetine is 30 mg once daily for one week, then increasing to 60 mg once daily as the maintenance dose, with some patients requiring up to 120 mg daily 1.
• Treatment duration is typically long-term for chronic pain conditions, with regular reassessment every 3-6 months.
• Duloxetine works by inhibiting the reuptake of serotonin and norepinephrine, neurotransmitters that help regulate pain signals in the central nervous system, providing a dual action to reduce pain perception and improve pain thresholds.
• Common side effects include nausea, dry mouth, constipation, decreased appetite, fatigue, drowsiness, and increased sweating, which often improve after the first few weeks of treatment 1.
• Patients should be aware that duloxetine should not be stopped abruptly but tapered gradually to avoid discontinuation symptoms.

Benefits and Considerations

• Duloxetine is particularly useful for patients who cannot take NSAIDs due to gastrointestinal, renal, or cardiovascular concerns, and it may provide additional benefit for those with comorbid depression or anxiety alongside their pain condition 1.
• The evidence suggests that duloxetine is associated with small to moderate, primarily short-term effects on pain, and improvements in function are generally smaller 1.
• Recent studies have shown that duloxetine achieved significant reductions in pain outcomes for patients with OA, and a statistically significant improvement in physical function for patients taking duloxetine 1.

Important Recommendations

• Duloxetine should be initiated at doses 30 mg/d or more and increased to a goal of 60 mg/d, with patients educated to take it daily and not as needed, and to discontinue only after consultation with their prescribing provider 1.
• When discontinuing duloxetine, it should be tapered over at least 2 to 4 weeks for those treated with therapy longer than 3 weeks to avoid discontinuation symptoms 1.

From the FDA Drug Label

A total of 354 patients (234 duloxetine delayed-release capsules, 120 placebo) were enrolled in Study FM-1 and a total of 520 patients (376 duloxetine delayed-release capsules, 144 placebo) were enrolled in Study FM-2 (5% male, 95% female). The patients had a baseline pain score of 6. 5 on an 11-point scale ranging from 0 (no pain) to 10 (worse possible pain). Studies FM-1 and FM-2 compared duloxetine delayed-release capsules 60 mg once daily or 120 mg daily (given in divided doses in Study FM-1 and as a single daily dose in Study FM-2) with placebo Study FM-2 additionally compared duloxetine delayed-release capsules 20 mg with placebo during the initial three months of a six-month trial. Treatment with duloxetine delayed-release capsules 60 mg or 120 mg daily statistically significantly improved the endpoint mean pain scores from baseline and increased the proportion of patients with at least a 50% reduction in pain score from baseline Pain reduction was observed in patients both with and without comorbid MDD. However, the degree of pain reduction may be greater in patients with comorbid MDD. 14. 6 Chronic Musculoskeletal Pain in Adults Duloxetine delayed-release capsules are indicated for the treatment of chronic musculoskeletal pain in adults. This has been established in trials in adult patients with chronic low back pain and chronic pain due to osteoarthritis Trials in Chronic Low Back Pain in Adults The efficacy of duloxetine delayed-release capsules in chronic low back pain (CLBP) in adults was assessed in two double-blind, placebo-controlled, randomized clinical trials of 13-weeks duration (Studies CLBP-1 and CLBP-2), and one of 12-weeks duration (CLBP-3) Studies CLBP-1 and CLBP-3 demonstrated efficacy of duloxetine delayed-release capsules in the treatment of CLBP. Patients in all trials had no signs of radiculopathy or spinal stenosis. Study CLBP-1: Two hundred thirty-six adult patients (N=115 on duloxetine delayed-release capsules, N=121 on placebo) enrolled and 182 (77%) completed 13-week treatment phase After 7 weeks of treatment, duloxetine delayed-release capsules-treated patients with less than 30% reduction in average daily pain and who were able to tolerate 60 mg once daily had their duloxetine delayed-release capsules dosage, in a double-blinded fashion, increased to 120 mg once daily for the remainder of the trial Patients had a mean baseline pain rating of 6 on a numerical rating scale ranging from 0 (no pain) to 10 (worst possible pain). After 13 weeks of treatment, patients taking duloxetine delayed-release capsules 60 to 120 mg daily had a significantly greater pain reduction compared to patients taking placebo. Randomization was stratified by the patients’ baseline NSAIDs use status Subgroup analyses did not indicate that there were differences in treatment outcomes as a function of NSAIDs use Study CLBP-2: Four hundred and four patients were randomized to receive fixed dosages of duloxetine delayed-release capsules daily or a matching placebo (N=59 on duloxetine delayed-release capsules 20 mg, N=116 on duloxetine delayed-release capsules 60 mg, N=112 on duloxetine delayed-release capsules 120 mg, N=117 on placebo) and 267 (66%) completed the entire 13-week trial After 13 weeks of treatment, none of the three duloxetine delayed-release capsules dosages showed a statistically significant difference in pain reduction compared to placebo Study CLBP-3: Four hundred and one patients were randomized to receive fixed doses of duloxetine delayed-release capsules 60 mg daily or placebo (N=198 on duloxetine delayed-release capsules, N=203 on placebo), and 303 (76%) completed the trial. Patients had a mean baseline pain rating of 6 on a numerical rating scale ranging from 0 (no pain) to 10 (worst possible pain) After 12 weeks of treatment, patients taking duloxetine delayed-release capsules 60 mg daily had significantly greater pain reduction compared to patients taking placebo.

Duloxetine for Arthritis or Chronic MSK Pain

• Indication: Duloxetine delayed-release capsules are indicated for the treatment of chronic musculoskeletal pain in adults, including chronic low back pain and chronic pain due to osteoarthritis.
• Efficacy: Studies have demonstrated the efficacy of duloxetine delayed-release capsules in the treatment of chronic low back pain and chronic pain due to osteoarthritis.
• Dosage: The recommended dosage is 60 mg daily, with some patients benefiting from an increase to 120 mg daily.
• Key Findings:
  • Patients taking duloxetine delayed-release capsules 60 to 120 mg daily had a significantly greater pain reduction compared to patients taking placebo.
  • Subgroup analyses did not indicate that there were differences in treatment outcomes as a function of NSAIDs use.
  • After 12 weeks of treatment, patients taking duloxetine delayed-release capsules 60 mg daily had significantly greater pain reduction compared to patients taking placebo. 2

From the Research

Duloxetine for Arthritis or Chronic MSK Pain

• Duloxetine is a serotonin-norepinephrine reuptake inhibitor that has been studied for its effectiveness in treating chronic musculoskeletal pain, including arthritis and chronic low back pain 3, 4, 5, 6.
• A systematic review and meta-analysis found that duloxetine was effective in reducing pain and improving quality of life in patients with chronic musculoskeletal pain, with no significant difference in serious adverse events compared to placebo 5.
• Another study found that duloxetine was moderately efficacious in reducing pain intensity and improving mood in patients with chronic pain, including musculoskeletal pain, with moderate-certainty evidence 4.
• A study protocol for a randomized controlled trial found that combination treatment with duloxetine and cognitive behavioral therapy with phone-based support may be effective in treating chronic musculoskeletal pain, and that phone-based motivational interviewing may enhance treatment outcomes 7.
• The role of duloxetine in managing chronic musculoskeletal pain is still evolving, but it may be a useful treatment option for patients who have not responded to other treatments 6.

Efficacy of Duloxetine

• Duloxetine has been shown to be effective in reducing pain intensity and improving quality of life in patients with chronic musculoskeletal pain 5.
• The efficacy of duloxetine in reducing pain intensity and improving mood has been found to be moderate, with moderate-certainty evidence 4.
• Duloxetine has been found to be effective in improving physical function and reducing pain interference in patients with chronic musculoskeletal pain 5.

Safety of Duloxetine

• The safety of duloxetine in patients with chronic musculoskeletal pain has been found to be similar to that of placebo, with no significant difference in serious adverse events 5.
• The certainty of evidence for the safety of duloxetine is low, and further studies are needed to fully understand its safety profile 4.