Maximum Recommended Dose of Duloxetine (Cymbalta)
The maximum recommended dose of duloxetine is 120 mg per day, though for most indications 60 mg daily 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 1
- No evidence that doses higher than 60 mg provide additional significant benefit 1, 3
- Higher dosages are less well tolerated 1
- For patients with tolerability concerns, a lower starting dose may be considered 1
Fibromyalgia
- Recommended dose: 60 mg once daily 1
- Start at 30 mg once daily for 1 week to improve tolerability 1
- No evidence that doses greater than 60 mg/day confer additional benefit 1, 4
- Higher dosages associated with higher rates of adverse reactions 1
Generalized Anxiety Disorder
- Adults under 65: 60 mg once daily 1
- 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, 5
- Geriatric patients: Start at 30 mg once daily for 2 weeks before considering increase to 60 mg/day 1
- Pediatric patients (7-17 years): 30-60 mg once daily 1
Major Depressive Disorder
- Recommended starting dose: 40-60 mg/day (given as 20 mg twice daily or 60 mg once daily) 1
- While 120 mg/day dose was shown to be effective, there is no evidence that doses greater than 60 mg/day confer additional benefits 1
Dose Titration Considerations
- For most indications, starting at a lower dose (30 mg daily) for 1 week may improve tolerability 2
- The most common adverse effect is nausea, which can be reduced by starting at 30 mg once daily before increasing to 60 mg 2
- For patients with renal impairment, consider a lower starting dose and gradual increase 1
- Duloxetine is contraindicated in patients with severe hepatic and renal impairment 2
Adverse Effects and Tolerability
- Adverse events are dose-dependent, with higher rates at 120 mg compared to 60 mg daily 4
- Common side effects include nausea, dry mouth, headache, constipation, dizziness, somnolence, and fatigue 2, 6
- Most adverse events are mild to moderate in severity 5, 4
- Approximately 16% of patients discontinue treatment due to adverse effects 4
- Serious adverse events are rare 4
Important Clinical Considerations
- Duloxetine does not seem to produce clinically important electrocardiographic or blood pressure changes 2
- Unlike tricyclic antidepressants, duloxetine does not have the same cardiac toxicity concerns 2
- Duloxetine should not be used in combination with CYP1A2 inhibitors or nonselective, irreversible monoamine oxidase inhibitors 6
- For neuropathic pain management, duloxetine 60 mg daily has demonstrated efficacy with a number needed to treat of 5 for diabetic peripheral neuropathy 4
In summary, while duloxetine can be prescribed up to 120 mg daily, the optimal therapeutic dose for most indications is 60 mg daily, as higher doses generally do not provide additional benefits but do increase the risk of adverse effects.