Baseline Dosing for Duloxetine (Cymbalta)
The baseline dosing for duloxetine is 30 mg once daily for one week, then increasing to 60 mg once daily as the standard therapeutic dose for most indications. 1
Initial Dosing by Indication
Diabetic Peripheral Neuropathic Pain
- Standard dose: 60 mg once daily 1
- For patients with tolerability concerns: Start at 30 mg once daily for one week before increasing to 60 mg once daily 1
- No evidence that doses higher than 60 mg provide additional benefit 1, 2
Major Depressive Disorder
- Starting dose: 40 mg/day (given as 20 mg twice daily) to 60 mg/day (given either once daily or as 30 mg twice daily) 1
- Alternative approach: Start at 30 mg once daily for 1 week, then increase to 60 mg once daily 1
- Maximum effective dose: 60 mg/day (doses up to 120 mg/day were studied but showed no additional benefit) 1, 3
Generalized Anxiety Disorder
- Adults <65 years: 60 mg once daily 1
- For tolerability: Start at 30 mg once daily for 1 week before increasing to 60 mg 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
Fibromyalgia
- Recommended dose: 60 mg once daily 1
- Start at 30 mg once daily for 1 week before increasing to 60 mg 1, 2
Administration Guidelines
- Take orally with or without food 1
- Swallow capsules whole - do not chew, crush, or open the capsules 1
- If a dose is missed, take it as soon as remembered unless it's almost time for the next dose 1
- Do not take two doses at the same time 1
Dose Adjustments
Renal Impairment
Adjust dose based on creatinine clearance 4:
- CrCl ≥60 mL/min: 300-600 mg/day (standard dosing)
- CrCl 30-59 mL/min: 150-300 mg/day
- CrCl 15-29 mL/min: 75-150 mg/day
- CrCl <15 mL/min: 25-75 mg/day
Common Side Effects
- Most common: Nausea, dry mouth, headache, constipation, dizziness, and fatigue 5
- Most side effects are mild to moderate in severity 5, 6
- Nausea is the most common reason for discontinuation 5
- Side effects are dose-dependent, with higher incidence at 120 mg compared to 60 mg 6
Important Considerations
- Duloxetine is a serotonin and norepinephrine reuptake inhibitor (SNRI) 5, 3
- For neuropathic pain, duloxetine 60 mg daily has demonstrated efficacy with an NNT of 5 6
- Monitor for development or worsening of neuropsychiatric issues (depression, suicidal ideation) 7
- Avoid abrupt discontinuation - taper gradually to prevent discontinuation symptoms 5
- Contraindicated in patients taking MAOIs 7
Efficacy Evidence
- In diabetic peripheral neuropathy, 60 mg daily is effective with a risk ratio for ≥50% pain reduction of 1.73 (95% CI 1.44 to 2.08) 6
- For fibromyalgia, 60 mg daily shows efficacy with a risk ratio for ≥50% pain reduction of 1.57 (95% CI 1.20 to 2.06) 6
- Duloxetine demonstrates linear, dose-dependent pharmacokinetics across the 40-60 mg/day range 3
Remember that while higher doses (up to 120 mg/day) have been studied, there is generally no evidence of additional benefit beyond 60 mg/day for most indications, and higher doses are associated with increased side effects 1, 2, 6.