Duloxetine (Cymbalta) Dosing Recommendations
The recommended starting dose 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
Dosing by Indication
Major Depressive Disorder
- Starting dose: 30 mg once daily for 1 week
- Target dose: 60 mg once daily
- Maximum dose: While 120 mg/day has been studied, there is no evidence that doses higher than 60 mg/day confer additional benefit 1, 2
Generalized Anxiety Disorder
- Adults <65 years: Start at 30 mg once daily for 1 week, then increase to 60 mg once daily
- Geriatric patients: Start at 30 mg once daily for 2 weeks before considering increase to 60 mg once daily
- Pediatric patients (7-17 years): Start at 30 mg once daily for 2 weeks before considering increase to 60 mg once daily 1, 3
Diabetic Peripheral Neuropathic Pain
- Standard dose: 60 mg once daily
- Lower starting dose may be considered for patients with tolerability concerns
- No evidence that doses higher than 60 mg confer additional benefit 1, 4
Fibromyalgia
- Starting dose: 30 mg once daily for 1 week
- Target dose: 60 mg once daily
- No evidence that doses higher than 60 mg/day confer additional benefit 1, 4
Chronic Musculoskeletal Pain
- Starting dose: 30 mg once daily for 1 week
- Target dose: 60 mg once daily
- No evidence that higher doses confer additional benefit 1, 4
Administration Considerations
Food Effect
- Duloxetine may be administered without regard to food or time of day 3
- Taking duloxetine with food can improve initial tolerability, particularly when starting at 60 mg once daily 5
Dose Adjustment for Special Populations
Renal Impairment
- GFR ≥60 mL/min: 300-600 mg/day (standard dosing)
- GFR 30-59 mL/min: 150-300 mg/day
- GFR 15-29 mL/min: 75-150 mg/day
- GFR <15 mL/min: 25-75 mg/day
- Avoid use in severe renal impairment (GFR <30 mL/min) 6, 1
Hepatic Impairment
- Avoid use in chronic liver disease or cirrhosis 1
Elderly Patients
- Start at 30 mg once daily and titrate more slowly
- For GAD, maintain 30 mg once daily for 2 weeks before considering increase 1, 6
Discontinuation
- Gradual reduction rather than abrupt cessation is recommended
- Common discontinuation symptoms include dizziness, headache, nausea, diarrhea, paresthesia, irritability, vomiting, insomnia, anxiety, hyperhidrosis, and fatigue 1
Common Side Effects to Monitor
- Most common: nausea, dry mouth, headache, constipation, dizziness, and fatigue
- Most side effects are mild to moderate in severity
- Nausea is the most common reason for early discontinuation 3, 7
Important Precautions
- Allow at least 14 days between discontinuation of an MAOI and initiation of duloxetine
- Allow at least 5 days after stopping duloxetine before starting an MAOI
- Do not use with linezolid or intravenous methylene blue due to risk of serotonin syndrome 1
Clinical Pearls
- Starting at 30 mg once daily for one week before increasing to 60 mg significantly improves tolerability 5, 7
- Taking duloxetine with food can reduce initial nausea, particularly when starting at 60 mg 5
- For most indications, there is no evidence that doses higher than 60 mg/day provide additional benefit, but they may increase side effects 1, 2, 7
- Steady state is typically reached by day 3 of administration 3