What is the use of duloxetine (Cymbalta)?

From the Guidelines

Duloxetine is recommended as a first-line treatment for neuropathic pain, particularly for diabetic peripheral neuropathy, at a dose of 60 mg once daily. This recommendation is based on the most recent and highest quality study available, which demonstrated the efficacy and safety of duloxetine in reducing neuropathic pain and improving quality of life 1.

Key Points to Consider

• Duloxetine belongs to a class of drugs called serotonin-norepinephrine reuptake inhibitors (SNRIs), which work by increasing levels of serotonin and norepinephrine in the brain to help maintain mental balance and reduce pain signals.
• The typical starting dose for pain conditions is 30 mg once daily, which may be increased to 60 mg daily after one week.
• Common side effects include nausea, dry mouth, constipation, decreased appetite, fatigue, drowsiness, and increased sweating.
• Duloxetine should be taken at the same time each day, with or without food, and the capsules should be swallowed whole.
• It's essential to note that duloxetine shouldn't be stopped abruptly as this can cause withdrawal symptoms; dosage should be gradually reduced under medical supervision.

Monitoring and Follow-Up

• Patients should be monitored for worsening depression or suicidal thoughts, particularly when starting treatment or changing doses.
• The medication may take 2-4 weeks to show full therapeutic effects.
• Regular follow-up appointments are necessary to assess the effectiveness of duloxetine and adjust the treatment plan as needed.

Comparison with Other Treatments

• Duloxetine has been shown to be effective in reducing neuropathic pain and improving quality of life, with a relatively favorable safety profile compared to other treatments such as opioids 1.
• Other treatments, such as tapentadol, have been found to have inconclusive evidence supporting their effectiveness and carry a high risk of addiction and safety concerns 1.

Special Considerations

• Duloxetine may be used in combination with other medications, such as gabapentin or pregabalin, for patients with inadequate pain relief 2.
• Patients with cardiac disease or ventricular conduction abnormalities should be prescribed duloxetine with caution, and dosage adjustments may be necessary 2.

From the FDA Drug Label

1. Indications and Usage

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

• Duloxetine is used 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, and Chronic Musculoskeletal Pain in adults 3.
• The safety and effectiveness of duloxetine have been established for treatment of Generalized Anxiety Disorder (GAD) in patients 7 to 17 years of age, but not for Major Depressive Disorder (MDD), Diabetic Peripheral Neuropathic Pain, or Chronic Musculoskeletal Pain in pediatric patients 4.
• Antidepressants, including duloxetine, increased the risk of suicidal thoughts and behavior in pediatric patients, and all pediatric patients being treated with antidepressants should be monitored for clinical worsening and emergence of suicidal thoughts and behaviors 5.

From the Research

Overview of Duloxetine

• Duloxetine is a selective dual neuronal serotonin (5-Hydroxytryptamine, 5-HT) and norepinephrine reuptake inhibitor (SSNRI) 6.
• 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) 6, 7.

Efficacy of Duloxetine

• 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 6.
• Duloxetine has been shown to be effective in the short- and long-term treatment of MDD, with significant improvements in core emotional symptoms and painful physical symptoms associated with depression 8, 9.
• A systematic review of 85 studies confirmed the efficacy, safety, and tolerability of duloxetine in the treatment of MDD, GAD, neuropathic pain, fibromyalgia, and stress incontinence urinary 7.

Safety and Tolerability of Duloxetine

• Duloxetine is generally well tolerated, although it may be appropriate to avoid initiating treatment with the 60 mg/day dosage due to a higher discontinuation rate due to adverse events in some studies 8, 9.
• The most frequently reported treatment-emergent adverse events include nausea, headache, dry mouth, dizziness, and insomnia 9.
• The incidence of treatment-emergent nausea is higher among patients receiving duloxetine 60 mg QD compared to those receiving 20 mg BID 9.

Expansions Beyond Major Depression and Generalized Anxiety Disorder

• Duloxetine may be an effective treatment for mood spectrum disorders, panic disorder, several symptom clusters of borderline personality, and as add-on drug in schizophrenia 10.
• Modest or conflicting results have been found for the efficacy of duloxetine in obsessive-compulsive disorder, posttraumatic stress disorder, eating, and sexual disorders 10.