What is the recommended dose for duloxetine (Cymbalta)?

Duloxetine Dosing Recommendations

For most indications, start duloxetine at 30 mg once daily for 1 week to improve tolerability and reduce nausea, then increase to the target dose of 60 mg once daily. 1, 2

Standard Dosing by Indication

Major Depressive Disorder (MDD)

• Starting dose: 40-60 mg/day (can give as 20 mg twice daily, 30 mg twice daily, or 60 mg once daily) 3
• Preferred approach: Begin at 30 mg once daily for 1 week before increasing to 60 mg once daily to allow adjustment and minimize nausea 3
• Target dose: 60 mg once daily 3
• Maximum dose: While 120 mg/day has shown efficacy, there is no evidence that doses above 60 mg/day provide additional benefit 3

Generalized Anxiety Disorder (GAD)

• Adults <65 years: Start at 60 mg once daily (or 30 mg once daily for 1 week if tolerability is a concern), target 60 mg once daily 3
• Geriatric patients (≥65 years): Start at 30 mg once daily for 2 weeks before increasing to 60 mg/day 3
• Pediatric patients (7-17 years): Start at 30 mg once daily for 2 weeks, then consider increasing to 60 mg once daily; dosage range 30-60 mg once daily 3
• Dose escalation: If needed beyond 60 mg once daily, increase in 30 mg increments (maximum studied: 120 mg/day) 3

Diabetic Peripheral Neuropathic Pain

• Dose: 60 mg once daily 3
• Important: No evidence that doses >60 mg/day provide additional benefit, and higher doses are less well tolerated 3
• Renal considerations: Since diabetes frequently involves renal disease, consider lower starting dose with gradual titration in patients with renal impairment 3

Fibromyalgia

• Starting dose: 30 mg once daily for 1 week 3
• Target dose: 60 mg once daily 3
• Key point: Some patients respond to the 30 mg starting dose; no evidence that doses >60 mg/day provide additional benefit, and higher doses increase adverse reactions 3

Chronic Musculoskeletal Pain

• Starting dose: 30 mg once daily for 1 week 2, 3
• Target dose: 60 mg once daily 2, 3
• Evidence: Higher doses do not confer additional benefit and are associated with higher adverse reaction rates 2, 3

Administration Guidelines

How to Take

• Swallow capsules whole with or without food 3
• Do not chew, crush, open, or sprinkle contents on food or mix with liquids, as this affects the enteric coating 3
• Missed dose: Take as soon as remembered unless it's almost time for the next dose; never double dose 3

Special Populations

Renal Impairment

• Severe renal impairment (GFR <30 mL/min): Avoid use 3
• Mild-moderate renal impairment: Consider lower starting dose with gradual titration 2, 3

Hepatic Impairment

• Chronic liver disease or cirrhosis: Avoid use 3

Elderly Patients

• Start with lower doses (30 mg once daily) and titrate more slowly 1, 2
• For GAD specifically, use 30 mg once daily for 2 weeks before considering increase to 60 mg/day 3

Critical Safety Considerations

Discontinuation

• After >3 weeks of treatment: Taper over at least 2-4 weeks to minimize discontinuation symptoms 2
• Discontinuation symptoms include: Dizziness, headache, nausea, diarrhea, paresthesia, irritability, vomiting, insomnia, anxiety, hyperhidrosis, and fatigue 3

Common Adverse Effects

• Nausea, dry mouth, constipation, dizziness, and fatigue are most common 1
• Nausea is the primary reason for discontinuation in clinical trials 1
• Most adverse events occur with initial dosing at 60 mg; subsequent dose escalations produce fewer additional adverse events 4

Drug Interactions

• Contraindicated with MAOIs due to serotonin syndrome risk 1
• Avoid concomitant use with potent CYP1A2 inhibitors 5
• Use caution with drugs extensively metabolized by CYP2D6, particularly those with narrow therapeutic index 5

Monitoring

• Routine aminotransferase monitoring is generally unnecessary 2
• Blood pressure changes are typically not clinically significant 2

Clinical Pearls

The 30 mg starting dose for 1 week is crucial for tolerability — this approach significantly reduces nausea and improves treatment adherence compared to starting at 60 mg directly 1, 2, 3. The majority of adverse events occur during the first week at 60 mg, not with subsequent dose escalations 4.