Duloxetine (Cymbalta) Dosing and Administration Guidelines
The recommended dose of duloxetine (Cymbalta) is 60 mg once daily for most indications, with specific dosing adjustments based on the condition being treated and patient factors. 1
Dosing by Indication
Diabetic Peripheral Neuropathic Pain
- Standard dose: 60 mg once daily 1
- No evidence that doses higher than 60 mg provide additional benefit 1
- For patients with tolerability concerns, may start at 30 mg once daily for 1 week before increasing to 60 mg 1
- Efficacy maintained throughout 12-week treatment periods with approximately 50% of patients achieving at least 50% pain reduction 2
Major Depressive Disorder
- Starting dose: 40-60 mg/day (given as 20 mg twice daily or 60 mg once daily) 1
- May start at 30 mg once daily for 1 week to allow adjustment before increasing to 60 mg once daily 1
- Maximum effective dose: 60 mg/day (no additional benefit at higher doses) 1
Generalized Anxiety Disorder
- Adults <65 years: 60 mg once daily 1
- May start at 30 mg once daily for 1 week before increasing to 60 mg once daily 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
- Begin at 30 mg once daily for 1 week before increasing to 60 mg 1
Administration Guidelines
- Take orally with or without food 1
- Swallow capsules whole; do not chew, crush, open, or sprinkle contents 1
- If a dose is missed, take as soon as remembered unless it's almost time for the next dose 1
- Do not take two doses at the same time 1
Special Populations
Renal Impairment
- Consider lower starting dose and gradual increase for patients with renal impairment 1
- Dosage adjustment based on creatinine clearance 3:
- ≥60 mL/min: 900-3600 mg/day (standard dosing)
- 30-59 mL/min: 400-1400 mg/day (reduced dosing)
- 15-29 mL/min: 200-700 mg/day (significantly reduced dosing)
- ≤15 mL/min: 100-300 mg/day (minimal dosing)
Elderly Patients
- Start at lower doses (30 mg once daily) and titrate more slowly 3
- Monitor closely for side effects, including cognitive impairment 3
Efficacy Considerations
- For diabetic neuropathic pain, the number needed to treat (NNT) to achieve at least 50% pain reduction is 4.9 for 120 mg/day and 5.2 for 60 mg/day 2
- For fibromyalgia, duloxetine shows efficacy at 60-120 mg daily with a risk ratio for ≥50% pain reduction of 1.57 (NNTB 8) 4
- Duloxetine 60 mg once daily has been shown effective for chronic musculoskeletal pain conditions 5
Common Side Effects and Monitoring
- Most common adverse effects: nausea, dry mouth, headache, constipation, dizziness, and fatigue 6
- Side effects are typically mild to moderate and often transient 6
- Discontinuation-emergent adverse events (most commonly nausea and dizziness) may occur in up to one-third of patients 6
- Monitor blood pressure regularly, especially at higher doses 3
Important Considerations
- Avoid concomitant use with potent CYP1A2 inhibitors (e.g., fluvoxamine) as they can increase duloxetine exposure by up to 460% 7
- Smoking may decrease duloxetine concentration by approximately 30% 7
- Duloxetine may increase the exposure of drugs metabolized by CYP2D6 7
- Do not abruptly discontinue - taper gradually to minimize withdrawal symptoms
Clinical Decision Algorithm
- Assess indication: Determine primary condition requiring treatment
- Evaluate patient factors: Age, renal function, hepatic function, concomitant medications
- Select initial dose:
- Standard: 60 mg once daily for most adults
- Conservative: 30 mg once daily for 1-2 weeks before increasing to 60 mg
- Evaluate response at 12 weeks:
- If <5% improvement in symptoms, consider discontinuation or alternative medication
- If ≥50% improvement, continue at current dose
- Monitor for side effects and adjust as needed
Duloxetine's once-daily dosing regimen enhances convenience and may improve adherence compared to medications requiring multiple daily doses.