What is the role of duloxetine in managing pain?

From the Guidelines

Duloxetine is a recommended medication for managing chronic pain, particularly neuropathic pain, due to its efficacy in reducing pain intensity and improving quality of life, as shown in the most recent and highest quality study 1.

Key Points

• Duloxetine works by increasing serotonin and norepinephrine levels in the central nervous system, which helps inhibit pain signals.
• The typical starting dose is 30 mg once daily for one week, then increasing to 60 mg once daily if needed, with some patients requiring up to 120 mg daily, divided into two doses.
• Treatment duration varies based on the condition but is often continued for at least 3-6 months with periodic reassessment.
• Common side effects include nausea, dry mouth, constipation, decreased appetite, fatigue, and dizziness, which often improve over time.
• Duloxetine should be taken with food to reduce stomach upset and should not be stopped abruptly to avoid withdrawal symptoms.

Important Considerations

• Duloxetine is contraindicated with MAOIs and caution is needed in patients with liver disease, alcohol use, or bleeding disorders.
• Full pain relief may take 2-4 weeks to develop, so patience with treatment is important.
• The most recent study 1 found that duloxetine improved neuropathy-related quality of life and reduced pain intensity in patients with diabetic peripheral neuropathy.

Comparison with Other Medications

• Compared to other medications, such as tapentadol, duloxetine has a more favorable risk-benefit profile and is generally recommended as a first- or second-line therapy for chronic neuropathic pain 1.
• Pregabalin and gabapentin are also effective for pain control in diabetic neuropathy, but may have more severe adverse effects in older patients 1.

From the FDA Drug Label

The efficacy of duloxetine delayed-release capsules for the management of neuropathic pain associated with diabetic peripheral neuropathy in adults was established in 2 randomized, 12-week, double-blind, placebo-controlled, fixed-dose trials in adult patients having diabetic peripheral neuropathic pain (DPNP) for at least 6 months (Study DPNP-1 and Study DPNP-2).

The efficacy of duloxetine delayed-release capsules for the management of fibromyalgia in adults was established in two randomized, double-blind, placebo-controlled, fixed-dose trials in adult patients meeting the American College of Rheumatology criteria for fibromyalgia (a history of widespread pain for 3 months, and pain present at 11 or more of the 18 specific tender point sites).

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

Duloxetine's role in managing pain is to treat various types of pain, including:

• Diabetic Peripheral Neuropathic Pain (DPNP): duloxetine has been shown to statistically significantly improve endpoint mean pain scores from baseline and increase the proportion of patients with at least a 50% reduction in pain scores from baseline 2
• Fibromyalgia: duloxetine has been shown to statistically significantly improve the endpoint mean pain scores from baseline and increase the proportion of patients with at least a 50% reduction in pain score from baseline 2, 2
• Chronic Musculoskeletal Pain: duloxetine is indicated for the treatment of chronic musculoskeletal pain in adults, including chronic low back pain and chronic pain due to osteoarthritis 2, 2

From the Research

Role of Duloxetine in Managing Pain

Duloxetine is a balanced serotonin and noradrenaline reuptake inhibitor that has been licensed for the treatment of major depressive disorders, urinary stress incontinence, and the management of neuropathic pain associated with diabetic peripheral neuropathy 3, 4. The evidence suggests that duloxetine is effective in treating painful diabetic peripheral neuropathy, fibromyalgia, and chronic musculoskeletal pain due to chronic osteoarthritis pain and low back pain 3, 5, 4, 6, 7.

Efficacy of Duloxetine

• Duloxetine at 60 mg daily is effective in treating painful diabetic peripheral neuropathy in the short term, with a risk ratio for ≥ 50% pain reduction at 12 weeks of 1.73 (95% CI 1.44 to 2.08) 3.
• Duloxetine at 60 mg daily is also effective for fibromyalgia over 12 weeks (RR for ≥ 50% reduction in pain 1.57,95% CI 1.20 to 2.06) and over 28 weeks (RR 1.58,95% CI 1.10 to 2.27) 3, 4, 6.
• Duloxetine has been shown to significantly improve the symptoms of chronic pain associated with fibromyalgia and diabetic neuropathy, as measured by various outcome measures in several placebo-controlled, randomized, double-blind, multicenter studies 6.

Safety and Tolerability

• Adverse events were common in both treatment and placebo arms but more common in the treatment arm, with a dose-dependent effect 3, 4.
• Most adverse effects were minor, but 16% of participants stopped the drug due to adverse effects 3, 4.
• Serious adverse events were rare 3, 4.
• Treatment-emergent adverse events are generally mild to moderate in severity, and tend to occur early and transiently 7.