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

Duloxetine Titration

Start duloxetine at 30 mg once daily for 1 week, then increase to the therapeutic dose of 60 mg once daily. This approach significantly reduces treatment-emergent nausea while producing only a transient delay in therapeutic effect compared to starting at 60 mg daily 1, 2, 3.

Standard Titration Schedule

Week 1: Initial Dosing

• Begin at 30 mg once daily for the first week to allow patients to adjust to the medication before reaching therapeutic dose 1, 2, 3
• This starting approach reduces nausea incidence (16.4% vs 32.9% when starting at 60 mg) and overall nausea rates throughout treatment 4
• Taking duloxetine with food further improves tolerability, particularly if considering a 60 mg starting dose 5

Week 2 and Beyond: Therapeutic Dosing

• Increase to 60 mg once daily after the first week, which is the target therapeutic dose for most indications 1, 3
• The 60 mg daily dose can be given as a single daily dose or split into 30 mg twice daily 3
• For major depressive disorder, some patients may start at 40 mg/day (20 mg twice daily), though 60 mg/day is more common 3

Dose Escalation Above 60 mg (When Needed)

• If 60 mg daily provides inadequate response after 4 weeks, consider increasing in 30 mg increments 1, 3
• Maximum studied dose is 120 mg daily, though evidence does not consistently support additional benefit above 60 mg/day 1, 3
• When escalating from 60 mg to 120 mg once daily, the majority of adverse events occur at initial 60 mg dosing; subsequent escalations produce few additional adverse events 6
• Allow at least 1 week at each dose level before further increases 2

Indication-Specific Considerations

Diabetic Peripheral Neuropathic Pain

• Use 60 mg once daily as the standard dose 3
• No evidence supports doses higher than 60 mg/day for this indication 3
• Consider lower starting dose (30 mg daily) in patients with renal impairment, as diabetes frequently complicates renal function 3

Generalized Anxiety Disorder

• Adults <65 years: Start 30 mg daily for 1 week, then increase to 60 mg daily 3
• Geriatric patients ≥65 years: Start 30 mg daily for 2 weeks before increasing to 60 mg daily 3
• Pediatric patients 7-17 years: Start 30 mg daily for 2 weeks before considering increase to 60-120 mg daily 3

Fibromyalgia

• Begin at 30 mg once daily for 1 week, then increase to 60 mg once daily 3
• Some patients may respond to the 30 mg starting dose 3
• No evidence supports doses >60 mg/day even in non-responders 3

Osteoarthritis Pain

• Initiate at 30 mg/day or more, with a goal of 60 mg/day 1
• Must be taken daily (not as needed) 1

Special Populations

Renal Impairment

• Contraindicated in patients with creatinine clearance <30 mL/min 2
• Use lower starting doses and slower titration in patients with any degree of renal impairment 3

Hepatic Impairment

• Dose reduction required; avoid duloxetine in hepatic disease 2

Geriatric Patients

• Use lower starting doses and slower titration 1
• For GAD specifically, maintain 30 mg daily for 2 weeks before escalation 3

Discontinuation Protocol

Taper duloxetine gradually over at least 2-4 weeks when discontinuing after >3 weeks of treatment 1. For patients with history of withdrawal symptoms, use an even slower taper over 3-4 weeks with smaller decrements (e.g., 120 mg → 100 mg → 80 mg → 60 mg → 30 mg) 2.

Monitoring Requirements

• Assess for adverse effects at each follow-up visit, particularly with higher doses 2
• Monitor blood pressure as duloxetine can cause modest hypertension 2
• Evaluate therapeutic response using standardized pain or depression scales 2
• Watch closely for mood changes, particularly in young adults during first few months 1

Common Pitfalls to Avoid

• Do not start at 60 mg daily without food in tolerability-sensitive patients, as this produces the highest rate of nausea and discontinuation 5
• Do not open, crush, or chew delayed-release capsules, as this affects the enteric coating 3
• Do not abruptly discontinue after prolonged use; always taper to minimize withdrawal symptoms 1, 2
• Do not exceed 60 mg/day for diabetic neuropathy or fibromyalgia, as higher doses increase adverse effects without additional benefit 3