Maximum Recommended Dose of Duloxetine (Cymbalta)
The maximum recommended dose of duloxetine is 120 mg per day, though there is no evidence that doses greater than 60 mg per day confer additional benefits for most indications. 1
Dosing Guidelines by Indication
Diabetic Peripheral Neuropathic Pain
- Recommended dose: 60 mg once daily 1
- No evidence that doses higher than 60 mg once daily provide additional significant benefit 1
- Lower starting doses may be considered for patients with tolerability concerns 1
Fibromyalgia
- Recommended dose: 60 mg once daily 1
- Start at 30 mg once daily for 1 week to allow adjustment 1
- No evidence that doses greater than 60 mg/day confer additional benefit 1
Major Depressive Disorder
- Starting dose: 40-60 mg/day (given as 20 mg twice daily or 60 mg once daily) 1
- While 120 mg/day was shown to be effective, there is no evidence that doses greater than 60 mg/day confer additional benefits 1
Generalized Anxiety Disorder
- Adults <65 years: 60 mg once daily 1
- May start at 30 mg once daily for 1 week for adjustment 1
- Maximum studied dose: 120 mg per day 1
- Geriatric patients: Start at 30 mg once daily for 2 weeks before considering increase 1
Important Administration Considerations
Administration Method
- Take orally (with or without meals)
- Swallow capsules whole
- Do not chew, crush, open, or sprinkle contents 1
Dose Adjustments for Special Populations
- Renal impairment: Consider lower starting dose and gradual increase 1
- Elderly patients: Start with lower doses and titrate more slowly 2
Safety Considerations with Maximum Dosing
Adverse Effects
- Higher doses (120 mg) are associated with increased adverse reactions 1
- Common side effects include nausea, dry mouth, headache, decreased libido, dizziness, somnolence, and insomnia 3
- Nausea is commonly cited as the primary reason for discontinuation 4
Overdose Risk
- Fatal outcomes have been reported with acute overdoses, primarily with mixed overdoses but also with duloxetine alone 1
- 1000 mg (approximately 8.3 times the maximum recommended dose) has been associated with fatal outcomes 1
Evidence for Efficacy at Different Doses
- For diabetic peripheral neuropathy: 60 mg daily is effective with a risk ratio for 50% pain reduction of 1.65 (NNT 6) 5
- For fibromyalgia: 60 mg daily is effective over 12 weeks (RR 1.57, NNT 8) 5
- 20 mg daily is not efficacious for treating pain in diabetic peripheral neuropathy 6
Clinical Pearls
- Duloxetine 60 mg once-daily dosing is effective for managing diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain 7
- When increasing beyond 60 mg/day, increase in increments of 30 mg once daily 1
- Monitor patients closely when initiating treatment or changing doses, particularly for signs of worsening depression or suicidal thoughts
- Avoid abrupt discontinuation; taper gradually to minimize withdrawal symptoms
Remember that while 120 mg/day is the maximum dose studied and approved, most patients achieve optimal benefit at 60 mg/day with fewer side effects.