What is the recommended initial dose and titration schedule for duloxetine (Serotonin-Norepinephrine Reuptake Inhibitor)?

How to Start and Titrate Duloxetine

Start duloxetine at 30 mg once daily for 1 week to reduce nausea and improve tolerability, then increase to the target dose of 60 mg once daily for most indications. 1, 2, 3

Initial Dosing Strategy

The standard approach is 30 mg once daily for 1 week, followed by escalation to 60 mg once daily. 1, 2, 3 This starting regimen significantly reduces the incidence of nausea—the most common adverse effect—from 32.9% to 16.4% in the first week compared to starting at 60 mg. 4 While starting at 60 mg once daily is FDA-approved for some indications, the 30 mg lead-in week allows patients to adjust before reaching therapeutic dose. 5, 3

Alternative Starting Approaches by Indication

• Major Depressive Disorder: Either 40 mg/day (20 mg twice daily) or 60 mg/day (once daily or 30 mg twice daily) can be used, though 30 mg once daily for 1 week before escalation improves tolerability. 3

• Generalized Anxiety Disorder (adults <65 years): Start at 60 mg once daily, or use 30 mg once daily for 1 week if tolerability is a concern. 3

• Diabetic Peripheral Neuropathy: 60 mg once daily is the standard dose; for patients with tolerability concerns, consider a lower starting dose. 3

• Fibromyalgia and Chronic Musculoskeletal Pain: Begin at 30 mg once daily for 1 week, then increase to 60 mg once daily. 3

• Chemotherapy-Induced Peripheral Neuropathy: Use 30 mg daily for 1 week, then 60 mg daily. 5

Titration Beyond 60 mg Daily

Most patients should remain at 60 mg once daily, as there is no consistent evidence that higher doses provide additional benefit. 3 However, if escalation is deemed necessary:

• Increase in 30 mg increments at intervals of at least 1 week. 2, 5
• Maximum studied dose is 120 mg once daily. 3
• Higher doses (>60 mg/day) are associated with increased adverse events without clear additional efficacy. 3, 6

Special Populations

Elderly Patients (≥65 years)

• Start at 30 mg once daily for 2 weeks before considering increase to 60 mg/day. 3
• Titrate more slowly than in younger adults. 1, 2

Pediatric Patients (7-17 years with GAD)

• Start at 30 mg once daily for 2 weeks before considering increase to 60 mg. 3
• Recommended range is 30-60 mg once daily. 3

Renal Impairment

• Consider lower starting dose and gradual titration for patients with renal insufficiency. 1, 2
• Avoid use entirely in severe renal impairment (GFR <30 mL/min). 5, 3

Hepatic Impairment

• Avoid use in chronic liver disease or cirrhosis. 3
• Dose reduction is required in hepatic disease. 5

Administration Instructions

• Swallow capsules whole—do not chew, crush, or open the delayed-release capsule. 3
• Can be taken with or without meals. 3
• If a dose is missed, take it as soon as remembered unless it's almost time for the next dose; never double dose. 3

Monitoring During Titration

• Assess for adverse effects at each follow-up visit, particularly nausea, dry mouth, constipation, dizziness, and fatigue. 1, 5
• Monitor blood pressure as duloxetine can cause modest hypertension. 5
• Evaluate therapeutic response using standardized pain or depression scales. 5
• Routine aminotransferase monitoring is generally unnecessary. 2

Common Pitfalls to Avoid

• Do not combine with MAOIs due to risk of serotonin syndrome. 1
• Do not start at 60 mg in patients with tolerability concerns—the higher initial dose is associated with increased discontinuation rates in some studies. 4
• Do not abruptly discontinue after more than 3 weeks of treatment; taper over at least 2-4 weeks to minimize withdrawal symptoms (dizziness, headache, nausea, paresthesia, irritability). 2, 3
• For patients with history of withdrawal symptoms, use a slower taper over 3-4 weeks with smaller decrements (e.g., 120→100→80→60 mg). 5