What is Cymbalta (duloxetine) used for and what are its dosing recommendations?

Duloxetine (Cymbalta): Uses and Dosing Recommendations

Duloxetine (Cymbalta) is FDA-approved for major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain in adults, with specific dosing recommendations for each condition. 1

FDA-Approved Indications

• Major depressive disorder (MDD) in adults 1
• Generalized anxiety disorder (GAD) in adults and pediatric patients 7 years and older 1
• Diabetic peripheral neuropathic pain in adults 1
• Fibromyalgia in adults 1
• Chronic musculoskeletal pain in adults (including chronic low back pain and osteoarthritis pain) 1, 2

Dosing Recommendations by Condition

Diabetic Peripheral Neuropathic Pain

• Recommended dose: 60 mg once daily 1
• No evidence that doses higher than 60 mg provide additional benefit 1
• For patients with tolerability concerns, a lower starting dose may be considered 1
• For patients with renal impairment, consider lower starting dose with gradual increase 1

Fibromyalgia

• Recommended dose: 60 mg once daily 1
• Begin treatment at 30 mg once daily for 1 week to improve tolerability 1
• No evidence that doses greater than 60 mg/day provide additional benefit 1, 3

Chronic Musculoskeletal Pain

• Recommended dose: 60 mg once daily 1
• Begin treatment at 30 mg once daily for 1 week 1
• Higher doses do not confer additional benefit and increase adverse reactions 1, 2

Major Depressive Disorder

• Recommended dose: 40-60 mg/day (typically 60 mg once daily) 4
• Starting at 30 mg for one week may improve tolerability 1
• Doses of 60-120 mg/day have shown efficacy in clinical trials 4

Generalized Anxiety Disorder

• Adults under 65: 60 mg once daily 1
• May start at 30 mg once daily for 1 week to improve tolerability 1
• Geriatric patients: Start at 30 mg once daily for 2 weeks before considering increase to 60 mg 1
• Pediatric patients (7-17 years): Start at 30 mg once daily for 2 weeks before considering increase to 60 mg 1

Evidence for Efficacy

Neuropathic Pain

• Duloxetine is recommended as a first-line medication for neuropathic pain 5
• In diabetic peripheral neuropathy, duloxetine 60 mg and 120 mg daily showed significantly higher pain reduction rates (59%) compared to placebo (38%) 5
• The effect appears more pronounced in platinum-based chemotherapy-induced neuropathy than taxane-induced neuropathy 5

Chronic Pain with Depression

• Duloxetine's dual mechanism targeting both serotonin and norepinephrine pathways makes it particularly effective for patients with co-occurring pain and depression 6
• Unlike some antidepressants, duloxetine does not typically produce clinically important electrocardiographic or blood pressure changes 6

Safety Considerations

• Most common adverse effect is nausea, which can be mitigated by starting at a lower dose 6, 1
• Other common side effects include dry mouth, headache, constipation, dizziness, and fatigue 7
• Rare adverse effects include acid reflux (reported in approximately 1.38% of patients) 8
• Avoid use in patients with chronic liver disease or cirrhosis 1
• Avoid use in patients with severe renal impairment (GFR <30 mL/minute) 1
• Gradual dose reduction rather than abrupt discontinuation is recommended to prevent withdrawal symptoms 1
• Allow at least 14 days between discontinuing an MAOI and starting duloxetine 1

Clinical Pearls

• For most conditions, starting at 30 mg once daily for one week before increasing to the target dose of 60 mg improves tolerability 1, 2
• Duloxetine may be administered without regard to food or time of day 7
• When switching from other antidepressants to duloxetine, a cross-taper approach is recommended to minimize discontinuation symptoms 6
• Duloxetine is safer than tricyclic antidepressants for patients with cardiac disease 6