What is the use of duloxetine (Cymbalta)?

From the Guidelines

Duloxetine is recommended for the treatment of osteoarthritis (OA) pain, as it has been shown to achieve significant reductions in pain outcomes and improve physical function in patients with OA 1.

Key Points to Consider

• Duloxetine is a selective serotonin and norepinephrine reuptake inhibitor that is commonly used to treat depression, anxiety, and pain.
• The recommended dose of duloxetine for OA pain is 30 mg/d or more, increased to a goal of 60 mg/d 1.
• Patients should be educated to take duloxetine daily, not as needed, and to discontinue it only after consultation with their prescribing provider, with a tapering period of at least 2 to 4 weeks for those treated with therapy longer than 3 weeks 1.
• Common side effects of duloxetine include nausea, dry mouth, constipation, decreased appetite, fatigue, drowsiness, increased sweating, and dizziness, which often improve over time as the body adjusts to the medication.

Comparison with Other Treatments

• Duloxetine has been shown to be effective in reducing pain associated with OA, whereas opioids, including tramadol, have been found to have limited benefit with a high risk of adverse effects and are not recommended for the management of OA pain 1.
• Other treatments for OA pain, such as topical agents, acetaminophen, and nonsteroidal anti-inflammatory drugs (NSAIDs), may also be considered, but duloxetine is a viable option for patients who do not respond to these treatments or have contraindications to their use.

Special Considerations

• Patients with liver or kidney problems, glaucoma, or a history of seizures should be cautious when taking duloxetine, and their dose may need to be adjusted or the medication avoided altogether 1.
• Older patients may experience more severe adverse events with duloxetine, but these can be attenuated with lower doses and slower titrations 1.

From the FDA Drug Label

Duloxetine delayed-release capsules are indicated for the treatment of: Major depressive disorder in adults Generalized anxiety disorder in adults and pediatric patients 7 years of age and older Diabetic peripheral neuropathic pain in adults Fibromyalgia in adults Chronic musculoskeletal pain in adults

The main uses of duloxetine are to treat:

• Major depressive disorder in adults
• Generalized anxiety disorder in adults and pediatric patients 7 years of age and older
• Diabetic peripheral neuropathic pain in adults
• Fibromyalgia in adults
• Chronic musculoskeletal pain in adults 2

From the Research

Overview of Duloxetine

• Duloxetine is a selective dual neuronal serotonin (5-Hydroxytryptamine, 5-HT) and norepinephrine reuptake inhibitor (SSNRI) 3
• It is indicated in the United States for treatment of major depressive disorder (MDD), generalized anxiety disorder (GAD), and several chronic pain conditions, including management of diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain due to chronic osteoarthritis (OA) pain and chronic low back pain (LBP) 3

Efficacy and Safety

• The literature suggests that duloxetine 60 mg once-daily dosing is an effective option for the management of diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain due to chronic OA pain and chronic LBP 3
• A systematic review of 85 studies confirmed the efficacy, safety, and tolerability of duloxetine in short- and long-term treatments for various clinical conditions, including MDD, GAD, neuropathic pain, fibromyalgia, and stress incontinence urinary 4
• Duloxetine has a more balanced profile of binding at about 10:1 for 5HT and NE transporter binding, and is also a moderate inhibitor of CYP2D6 5

Clinical Use

• Duloxetine is approved for MDD, GAD, diabetic peripheral neuropathic pain, fibromyalgia, and musculoskeletal pain 5
• It may be an effective treatment for mood spectrum disorders, panic disorder, several symptom clusters of borderline personality, and as add-on drug in schizophrenia 6
• A study examining the safety and tolerability of duloxetine during a dose escalation from 60 mg/day to 120 mg/day found that rapid dose escalation is safe and tolerable, with most adverse events being mild and transient 7

Adverse Effects

• Common side effects of duloxetine include nausea, dry mouth, dizziness, constipation, insomnia, asthenia, and hypertension 5
• Duloxetine may cause serotonin syndrome when combined with MAOIs, and may increase blood pressure and pulse, although this is infrequently observed at doses below 225 mg per day 5