What is the recommended dosage and treatment duration for duloxetine (Serotonin-Norepinephrine Reuptake Inhibitor) in patients with major depressive disorder, generalized anxiety disorder, fibromyalgia, and neuropathic pain?

Duloxetine Dosing and Treatment Duration

Major Depressive Disorder

Start duloxetine at 30 mg once daily for 1 week, then increase to 60 mg once daily, which is the target therapeutic dose for most patients. 1

• The recommended starting dosage is 40 mg/day (20 mg twice daily) to 60 mg/day (once daily or 30 mg twice daily) 1
• For tolerability, initiate at 30 mg once daily for 1 week before advancing to 60 mg once daily 1
• Maximum dose is 120 mg/day, though no evidence supports additional benefit beyond 60 mg/day 1
• Treatment duration should be reassessed periodically for continued need and appropriate maintenance dosing 1

Generalized Anxiety Disorder

For adults under 65 years, initiate at 60 mg once daily, with option to start at 30 mg once daily for 1 week if tolerability is a concern. 1

Adults <65 Years

• Standard initiation: 60 mg once daily 1
• Alternative initiation: 30 mg once daily for 1 week, then increase to 60 mg once daily 1
• Doses above 60 mg/day show no additional benefit, though 120 mg/day was studied 1

Geriatric Patients (≥65 Years)

• Start at 30 mg once daily for 2 weeks before increasing to target dose of 60 mg/day 1
• May increase beyond 60 mg in 30 mg increments if needed, maximum studied dose 120 mg/day 1

Pediatric Patients (7-17 Years)

• Initiate at 30 mg once daily for 2 weeks before considering increase to 60 mg once daily 1
• Recommended range: 30-60 mg once daily, maximum studied dose 120 mg/day 1

Neuropathic Pain (Diabetic Peripheral Neuropathy)

Administer 60 mg once daily as the standard dose; no evidence supports higher doses and they are less well tolerated. 1

• The target dose is 60 mg once daily 2, 1
• For tolerability concerns, consider starting at 30 mg once daily for 1 week before increasing to 60 mg once daily 2
• Doses higher than 60 mg/day provide no additional significant benefit and are clearly less well tolerated 1
• Duloxetine is a first-line medication for diabetic peripheral neuropathic pain alongside tricyclic antidepressants, gabapentin, and pregabalin 2
• An adequate trial requires 6-8 weeks, including at least 2 weeks at maximum tolerated dosage 2
• Efficacy is sustained for up to 1 year in open-label trials 2
• Number needed to treat (NNT) for 50% pain reduction at 12 weeks is approximately 6 3, 4

Important Caveats for Diabetic Patients

• Since diabetes frequently complicates renal disease, consider lower starting dosage and gradual titration in patients with renal impairment 1
• Avoid use in severe renal impairment (GFR <30 mL/min) 1

Fibromyalgia

Begin at 30 mg once daily for 1 week, then increase to 60 mg once daily, which is the recommended maintenance dose. 1

• Standard protocol: 30 mg once daily for 1 week, then 60 mg once daily 1
• Some patients respond to the 30 mg starting dosage 1
• No evidence supports doses >60 mg/day, even in non-responders, and higher doses increase adverse reactions 1
• Duloxetine is FDA-approved and recommended as first-line treatment for fibromyalgia 2
• Efficacy demonstrated at 12 weeks (NNT 8) and sustained through 28 weeks 3

Chronic Musculoskeletal Pain (Osteoarthritis, Low Back Pain)

Start at 30 mg once daily for 1 week, then increase to 60 mg once daily for maintenance. 1

• Initial dose: 30 mg once daily for 1 week to allow adjustment 1
• Target dose: 60 mg once daily 1
• Higher dosages show no additional benefit and increase adverse reactions 1
• Duloxetine demonstrates small improvements in chronic low back pain and is recommended after insufficient response to nonpharmacologic approaches like exercise 2
• For osteoarthritis with multiple joints or incomplete response to topical NSAIDs, duloxetine is an appropriate systemic option 2

Common Adverse Effects and Management

Nausea is the most common adverse effect and can be minimized by starting at 30 mg once daily for 1 week before increasing to 60 mg once daily. 2

• Most common adverse effects: nausea, somnolence, dizziness, constipation, dry mouth, reduced appetite 2
• Approximately 16% of patients discontinue due to side effects 3
• Adverse events may be more severe in older adults but can be attenuated with lower doses and slower titration 2
• Duloxetine does not produce clinically important electrocardiographic or blood pressure changes 2
• Aminotransferase monitoring is unnecessary 2

Discontinuation Protocol

Taper duloxetine gradually rather than stopping abruptly to minimize discontinuation symptoms. 1

• Abrupt discontinuation can cause: dizziness, headache, nausea, diarrhea, paresthesia, irritability, vomiting, insomnia, anxiety, hyperhidrosis, and fatigue 1
• Always use gradual dose reduction when discontinuing 1

Contraindications and Special Populations

• Avoid in chronic liver disease or cirrhosis 1
• Avoid in severe renal impairment (GFR <30 mL/min) 1
• Allow 14 days between discontinuing MAOIs and starting duloxetine 1
• Allow 5 days after stopping duloxetine before starting MAOIs 1

Treatment Duration Considerations

• For neuropathic pain: Assess response after 6-8 weeks with at least 2 weeks at maximum tolerated dose 2
• For all indications: Periodically reassess to determine continued need for maintenance treatment 1
• Long-term efficacy demonstrated up to 1 year in diabetic neuropathy 2
• Sustained efficacy through 28 weeks in fibromyalgia 3