Duloxetine (Cymbalta) Dosing Recommendations
The recommended 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, with specific adjustments based on the condition being treated. 1, 2
Initial Dosing and Titration
- Start with 30 mg once daily for 1 week before increasing to 60 mg once daily to reduce the risk of nausea and improve initial tolerability 2
- Taking duloxetine with food can further improve tolerability, particularly when starting at higher doses 3
- For most indications, 60 mg once daily is the standard effective therapeutic dose 1, 2
Condition-Specific Dosing
Diabetic Peripheral Neuropathic Pain
- Standard dose: 60 mg once daily 1, 2
- There is no evidence that doses higher than 60 mg daily provide additional benefit for neuropathic pain 1, 4
- Duration of adequate trial: 4 weeks 2
Fibromyalgia
- Start with 30 mg once daily for 1 week, then increase to 60 mg once daily 1
- Maximum dose: 60 mg once daily (higher doses don't confer additional benefits but increase adverse effects) 1, 4
Chronic Musculoskeletal Pain
- Start with 30 mg once daily for 1 week, then increase to 60 mg once daily 1
- Maximum dose: 60 mg once daily 1, 4
Major Depressive Disorder and Generalized Anxiety Disorder
- Target dose: 60 mg once daily 1, 5
- Some patients may require up to 120 mg daily (in divided doses) 1, 5
- For geriatric patients, start with 30 mg once daily for 2 weeks before considering an increase 1
Special Populations
Renal Impairment
- For patients with renal insufficiency, consider a lower starting dose and gradual titration 1, 2
- Avoid use in severe renal impairment (GFR <30 mL/minute) 1
Hepatic Impairment
- Avoid use in patients with chronic liver disease or cirrhosis 1
Geriatric Patients
- Start with 30 mg once daily for 2 weeks before considering dose increases 1
- Titrate more slowly in elderly patients 2
Discontinuation
- Gradual dose reduction rather than abrupt discontinuation is recommended to minimize withdrawal symptoms 1
- Common discontinuation symptoms include dizziness, headache, nausea, paresthesia, irritability, anxiety, and fatigue 1, 6
Drug Interactions and Precautions
- Do not use with MAOIs - allow at least 14 days between discontinuing an MAOI and starting duloxetine 1
- Allow at least 5 days after stopping duloxetine before starting an MAOI 1
- Avoid concomitant use with potent CYP1A2 inhibitors 1, 6
- Use with caution in patients taking medications metabolized by CYP2D6, particularly those with narrow therapeutic indices 6
Common Adverse Effects
- Most common: nausea, dry mouth, headache, constipation, dizziness, and fatigue 5, 7
- Most adverse effects are mild to moderate in severity 6
- Nausea is the most common side effect but occurs less frequently when treatment is initiated at 30 mg daily and gradually titrated 7
Clinical Pearls
- Pain relief can begin within one week at the 60 mg daily dose 7
- Duloxetine does not typically produce clinically important electrocardiographic or blood pressure changes 2
- Routine aminotransferase monitoring is generally unnecessary 2
- Duloxetine has a generally favorable side effect profile compared to other medications used for neuropathic pain 7, 4