What is the recommended starting dose of Cymbalta (duloxetine) for adults?

Cymbalta (Duloxetine) Dosing for Adults

Start duloxetine at 30 mg once daily for 1 week, then increase to 60 mg once daily for most indications. 1

Standard Dosing by Indication

Major Depressive Disorder

• Starting dose: 40 mg/day (20 mg twice daily) to 60 mg/day (once daily or 30 mg twice daily) 1
• Alternative approach: Begin at 30 mg once daily for 1 week to improve tolerability before increasing to 60 mg once daily 2, 1
• Maximum dose: 60 mg/day is the recommended target; while 120 mg/day has shown efficacy, no evidence supports additional benefit beyond 60 mg/day 1

Generalized Anxiety Disorder

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

Diabetic Peripheral Neuropathic Pain

• Recommended dose: 60 mg once daily 1
• Key point: No evidence that doses >60 mg/day provide additional significant benefit, and higher doses are clearly less well tolerated 3, 1
• For tolerability concerns: Consider lower starting dose, particularly in patients with renal impairment 1

Fibromyalgia

• Starting dose: 30 mg once daily for 1 week 1
• Target dose: 60 mg once daily 1
• Important: No evidence that doses >60 mg/day confer additional benefit; higher doses associated with increased adverse reactions 1

Chemotherapy-Induced Peripheral Neuropathy

• Dosing: 30 mg daily for 1 week, then 60 mg daily 2, 4
• Evidence quality: Reduction of neuropathic pain demonstrated, with better response in cisplatin-treated patients than taxane-treated patients 2

Administration Guidelines

How to Take

• Swallow capsules whole with or without food 1
• Do not chew, crush, or open capsules and mix contents with food/liquids (affects enteric coating) 1
• Missed dose: Take as soon as remembered unless almost time for next dose; never double dose 1

Tolerability Strategy

• Starting at 30 mg for 1 week reduces nausea, the most common adverse effect 5
• This approach allows patients to adjust before reaching therapeutic dose 2, 1

Special Populations

Renal Impairment

• Not recommended for creatinine clearance <30 mL/min 4
• Consider lower starting dose and gradual titration in patients with renal disease 1

Hepatic Impairment

• Contraindicated in severe hepatic impairment 5
• Dose reduction required in hepatic disease 2

Monitoring Requirements

• Blood pressure monitoring necessary as duloxetine can cause modest hypertension 4
• Assess for adverse effects at each follow-up visit, particularly with higher doses 4
• Evaluate therapeutic response using standardized pain or depression scales 4

Common Adverse Effects

The most frequent treatment-emergent adverse events include 5, 6:

• Nausea (most common, dose-related)
• Dry mouth
• Headache
• Constipation
• Dizziness
• Somnolence
• Fatigue

Nausea is significantly reduced by starting at 30 mg daily before escalating to 60 mg 5

Discontinuation

• Taper gradually over 3-4 weeks to minimize withdrawal symptoms 4
• Use small dose decrements (e.g., 120→100→80→60 mg) at weekly intervals for patients with history of withdrawal symptoms 4
• Discontinuation-emergent adverse events (commonly nausea and dizziness) occur in up to one-third of patients 6

Key Clinical Pitfalls

• Avoid exceeding 60 mg/day for diabetic neuropathy and fibromyalgia - no additional benefit and worse tolerability 3, 1
• Do not use with potent CYP1A2 inhibitors (duloxetine is a substrate) 6
• Use caution with CYP2D6-metabolized drugs with narrow therapeutic index (duloxetine is moderate CYP2D6 inhibitor) 6
• Unlike tricyclic antidepressants, duloxetine does not cause clinically important ECG changes or cardiac toxicity 5