What is the starting dose of duloxetine (Serotonin-Norepinephrine Reuptake Inhibitor - SNRI)?

Starting Dose of Duloxetine

Start duloxetine at 30 mg once daily for 1 week before increasing to the therapeutic dose of 60 mg once daily, which significantly reduces treatment-emergent nausea while producing only a transient delay in therapeutic effect. 1

Standard Dosing Protocol

The FDA-approved starting approach varies by indication, but the most tolerable strategy across conditions is to begin at 30 mg once daily 2:

Major Depressive Disorder

• Recommended starting dose: 30 mg once daily for 1 week, then increase to 60 mg once daily 1, 3
• Alternative FDA-approved approach: 40 mg/day (20 mg twice daily) to 60 mg/day can be used, but starting at 60 mg is associated with higher discontinuation rates due to nausea 2
• The 30 mg starting dose allows patients to adjust to the medication before reaching therapeutic levels 1

Generalized Anxiety Disorder

• Adults <65 years: Start at 30 mg once daily for 1 week, then increase to 60 mg once daily 2
• Geriatric patients (≥65 years): Start at 30 mg once daily for 2 weeks before increasing to 60 mg once daily 2
• Pediatric patients (7-17 years): Start at 30 mg once daily for 2 weeks before considering increase to 60 mg once daily 2

Diabetic Peripheral Neuropathic Pain

• Standard dose: 60 mg once daily 2
• For patients with tolerability concerns, consider starting at a lower dose 2
• Renal impairment requires lower starting dose and gradual titration 2

Fibromyalgia

• Start at 30 mg once daily for 1 week, then increase to 60 mg once daily 2
• Some patients may respond to the 30 mg starting dose 2

Chemotherapy-Induced Peripheral Neuropathy

• Start at 30 mg daily for 1 week, then increase to 60 mg daily 1

Critical Tolerability Considerations

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

• Starting at 30 mg once daily without food results in only 3.6% discontinuation due to adverse events, compared to 10.2% when starting at 60 mg without food 4
• When taken with food, discontinuation rates are similar across starting doses (5.4% vs 7.4%) 4
• Nausea is the most common adverse effect and the primary reason for discontinuation 1

Administration Guidelines

• Swallow capsules whole; do not chew, crush, or open the delayed-release capsule 2
• Can be taken with or without meals 2
• If a dose is missed, take as soon as remembered unless it's almost time for the next dose; never double dose 2

Special Population Adjustments

Hepatic Impairment

• Dose reduction is required 1
• Duloxetine is contraindicated in severe hepatic impairment 2

Renal Impairment

• Not recommended for creatinine clearance <30 mL/min 1
• Consider lower starting dose and gradual titration for any degree of renal impairment 2

Geriatric Patients

• Require lower starting doses (30 mg once daily) and slower titration 1, 3
• For GAD specifically, maintain 30 mg for 2 weeks before increasing 2

Monitoring Requirements

• Assess for adverse effects at each follow-up visit, particularly nausea in the first week 1
• Monitor blood pressure as duloxetine can cause modest hypertension 1
• Watch closely for mood changes in young adults during the first few months of treatment 1

Common Pitfall to Avoid

Do not start at 60 mg once daily without either (1) planning to take with food or (2) accepting higher discontinuation rates. The data clearly show that starting at 30 mg once daily for 1 week, regardless of food timing, produces the lowest discontinuation rate (3.6%) and allows patients to adjust before reaching therapeutic levels. 4 While the FDA label permits starting at 60 mg for some indications, the American College of Physicians and other guideline societies consistently recommend the 30 mg starting approach to optimize tolerability. 1, 3