Maximum Recommended Dose of Duloxetine
The maximum recommended dose of duloxetine is 120 mg per day, though for most indications 60 mg per day is considered the optimal therapeutic dose with no additional benefit demonstrated at higher doses. 1, 2
Dosing Guidelines by Indication
Diabetic Peripheral Neuropathic Pain
- Recommended dose: 60 mg once daily
- No evidence that doses higher than 60 mg confer additional benefit 1, 2
- For patients with tolerability concerns, a lower starting dose may be considered
- For patients with renal impairment, consider lower starting dose with gradual increase 1
Major Depressive Disorder
- Starting dose: 40-60 mg/day (given as 20 mg twice daily or 60 mg once daily)
- For some patients, starting at 30 mg once daily for 1 week may improve tolerability
- Maximum dose: 120 mg/day
- 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 under 65: 60 mg once daily (may start at 30 mg for 1 week for better tolerability)
- Geriatric patients: Start at 30 mg once daily for 2 weeks before considering increase to 60 mg
- Maximum dose studied: 120 mg per day
- While 120 mg once daily was shown to be effective, there is no evidence that doses greater than 60 mg/day confer additional benefit 1
Fibromyalgia
- Recommended dose: 60 mg once daily
- Start at 30 mg once daily for 1 week
- No evidence that doses greater than 60 mg/day confer additional benefit 1, 2
Important Clinical Considerations
Efficacy vs. Dose
- For most indications, 60 mg/day appears to be the optimal therapeutic dose
- Higher doses (up to 120 mg/day) do not consistently show additional benefit 2, 3
- In painful diabetic peripheral neuropathy, the NNT for 60 mg/day (5.2) is similar to 120 mg/day (4.9) 2
Safety Considerations
- Adverse effects are dose-dependent 4, 3
- Common side effects include nausea, somnolence, dizziness, constipation, dry mouth, and decreased appetite 2
- At higher doses, discontinuation rates due to adverse events increase 4
- Avoid use in patients with:
- Chronic liver disease or cirrhosis
- Severe renal impairment (GFR <30 mL/minute) 1
Dosing Schedule
- Once-daily dosing is generally recommended for 60 mg doses
- For higher doses (>60 mg), twice-daily dosing may be considered to improve tolerability 4
Discontinuation Protocol
- Gradual reduction in dosage rather than abrupt cessation is recommended to minimize withdrawal symptoms 1
- Common withdrawal symptoms include dizziness, headache, nausea, diarrhea, paresthesia, irritability, vomiting, insomnia, anxiety, hyperhidrosis, and fatigue
Special Populations
- Geriatric patients: Start at lower doses (30 mg/day) and titrate more slowly
- Renal impairment: Lower starting dose with gradual increase
- Hepatic impairment: Avoid use 1
While the absolute maximum dose studied is 120 mg per day, clinicians should carefully weigh the minimal additional benefit against the increased risk of adverse effects when considering doses above 60 mg per day for most indications.