What is the recommended starting dose of Cymbalta (duloxetine) for an adult patient with major depressive disorder, generalized anxiety disorder, or chronic pain?

Starting Dose of Cymbalta (Duloxetine)

Start duloxetine at 30 mg once daily for most patients, regardless of indication, to optimize tolerability before increasing to the therapeutic dose of 60 mg once daily after one week. 1

Indication-Specific Dosing Recommendations

Major Depressive Disorder

• Initial dose: 30 mg once daily for 1 week, then increase to 60 mg once daily 1
• Alternative approach: 40 mg/day (20 mg twice daily) to 60 mg/day can be used as starting doses, though the lower initial dose improves tolerability 1
• Maximum dose is 120 mg/day, but no evidence supports additional benefit beyond 60 mg/day 1

Generalized Anxiety Disorder

• Adults <65 years: Start 30 mg once daily for 1 week, then increase to 60 mg once daily 1
• Geriatric patients (≥65 years): Start 30 mg once daily for 2 weeks before increasing to 60 mg/day 1
• Pediatric patients (7-17 years): Start 30 mg once daily for 2 weeks before considering increase to 60 mg 1
• The recommended dosage range is 30-60 mg once daily, with maximum studied dose of 120 mg/day 1

Diabetic Peripheral Neuropathic Pain

• Standard dose: 60 mg once daily 1
• For tolerability concerns: Consider lower starting dose 1
• No evidence supports doses higher than 60 mg/day for this indication, and higher doses are clearly less well tolerated 1
• This aligns with guideline recommendations of 60-120 mg/day for painful diabetic neuropathy, though 60 mg is the FDA-approved dose 2, 3

Chronic Pain Conditions (Fibromyalgia, Chronic Musculoskeletal Pain)

• Start 30-60 mg daily, increase to 60-120 mg daily as needed 3
• The National Comprehensive Cancer Network recommends this approach for neuropathic pain as a first-line coanalgesic 3

Gastrointestinal Pain (Disorders of Gut-Brain Interaction)

• Start 30 mg once daily, titrate according to response and tolerability to maximum of 60 mg once daily 2
• This lower starting dose with gradual titration minimizes common side effects including sedation, dry mouth, constipation, diarrhea, anxiety, reduced appetite, nausea, headache, and fatigue 2

Critical Tolerability Strategy

Taking duloxetine with food significantly improves tolerability, especially when starting at 60 mg once daily. 4

• Starting at 30 mg once daily without food or 60 mg once daily with food both improve initial tolerability 4
• The food-by-dose interaction shows that taking medication with food provides greatest benefit for patients starting at 60 mg once daily 4
• Patients starting at 30 mg twice daily or 60 mg once daily without food had significantly higher discontinuation rates due to adverse events (14.0% and 10.2% respectively) compared to 30 mg once daily without food (3.6%) 4
• When taken with food, discontinuation rates were similar across all starting doses (5.4-7.5%) 4

Common Pitfalls and How to Avoid Them

Nausea is the most common reason for treatment discontinuation. 5, 4

• Most adverse events are mild to moderate in severity 5, 6
• Nausea, dry mouth, headache, constipation, dizziness, and fatigue are the most common treatment-emergent adverse events 5
• The adverse event profile does not differ with treatment duration 5
• Starting at 30 mg once daily for one week reduces early discontinuation rates 4

Special Population Considerations

Geriatric patients require slower titration due to increased sensitivity. 3, 1

• Use 30 mg once daily for 2 weeks before increasing to 60 mg/day in elderly patients with GAD 1
• This extended initial period allows better adjustment to the medication 3

Discontinuation Protocol

Never stop duloxetine abruptly—always taper gradually to avoid discontinuation syndrome. 3

• Discontinuation symptoms include dizziness, headache, nausea, diarrhea, paresthesia, irritability, vomiting, insomnia, anxiety, hyperhidrosis, and fatigue 3
• Discontinuation-emergent adverse events occurred in up to one-third of patients in short-term trials, most commonly nausea and dizziness 5

Administration Guidelines

• Swallow capsules whole—do not chew, crush, or open the delayed-release capsule 1
• Can be taken with or without meals, though with food improves tolerability when starting at higher doses 1, 4
• If a dose is missed, take as soon as remembered unless it's almost time for the next dose; never double dose 1