What is the recommended duloxetine dosing regimen for adults, including initial dose, titration, maximum dose, and adjustments for hepatic or renal impairment?

Duloxetine Dosage for Adults

Standard Initial Dosing

For most adult indications, start duloxetine at 30 mg once daily for 1 week, then increase to the target dose of 60 mg once daily. 1

• The 30 mg starting dose for the first week allows patients to adjust to the medication and significantly reduces the incidence of nausea, which is the most common adverse effect and primary reason for treatment discontinuation. 2, 3
• After 1 week at 30 mg daily, increase to 60 mg once daily, which is the therapeutic dose for most indications. 1

Maximum Dose and Dose Escalation

Do not exceed 60 mg once daily for most indications, as higher doses provide no additional benefit and significantly increase adverse effects. 1

• For generalized anxiety disorder in adults under 65 years, while 120 mg once daily has been studied, there is no evidence that doses greater than 60 mg daily confer additional benefit. 1, 4
• If a clinical decision is made to exceed 60 mg daily (only for GAD), increase in 30 mg increments. 1
• For diabetic peripheral neuropathic pain, chronic musculoskeletal pain, and fibromyalgia, there is no evidence that doses higher than 60 mg once daily provide additional benefit, and higher doses are clearly less well tolerated. 1

Indication-Specific Dosing

Major Depressive Disorder

• Start at 40-60 mg daily; may give as 20-30 mg twice daily or 40-60 mg once daily. 1
• Maximum dose: 120 mg daily, though doses above 60 mg rarely provide additional benefit. 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. 1
• Target dose: 60 mg once daily. 1

Diabetic Peripheral Neuropathic Pain

• Target dose: 60 mg once daily. 1
• For patients with tolerability concerns, start at 30 mg once daily. 1
• Since diabetes frequently involves renal disease, use a lower starting dose and gradual titration in patients with renal impairment. 1

Fibromyalgia

• Start at 30 mg once daily for 1 week, then increase to 60 mg once daily. 1
• Some patients may respond to the 30 mg starting dose. 1
• Doses greater than 60 mg daily do not provide additional benefit and increase adverse reactions. 1

Chronic Musculoskeletal Pain

• Start at 30 mg once daily for 1 week, then increase to 60 mg once daily. 1
• Higher doses do not confer additional benefit and increase adverse reactions. 1

Geriatric Patients (≥65 years)

In patients 65 years and older with generalized anxiety disorder, start at 30 mg once daily for 2 weeks before increasing to the target dose of 60 mg daily. 1

• After 2 weeks at 30 mg, increase to 60 mg daily. 1
• Some geriatric patients may benefit from doses above 60 mg; if increasing beyond 60 mg, use 30 mg increments. 1
• Maximum studied dose: 120 mg daily. 1

Hepatic Impairment

Avoid duloxetine in patients with chronic liver disease or cirrhosis. 1

• Duloxetine is extensively metabolized in the liver by CYP1A2 and CYP2D6. 5
• No dose adjustment is possible; the drug should not be used in hepatic impairment. 1

Renal Impairment

Avoid duloxetine in patients with severe renal impairment (GFR <30 mL/min). 1

• For mild to moderate renal impairment (creatinine clearance ≥30 mL/min), no dose adjustment is necessary. 6
• In end-stage renal disease, duloxetine exposure (Cmax and AUC) increases approximately 2-fold, and metabolite exposure increases up to 9-fold. 6
• For diabetic patients with neuropathic pain who have renal impairment, consider a lower starting dose and gradual titration. 1

Discontinuation

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

• Common discontinuation symptoms include dizziness, headache, nausea, diarrhea, paresthesia, irritability, vomiting, insomnia, anxiety, hyperhidrosis, and fatigue. 1
• Gradual dose reduction is recommended whenever possible. 1

Drug Interactions Affecting Dosing

Avoid concomitant use with potent CYP1A2 inhibitors (e.g., fluvoxamine), as they increase duloxetine exposure by 460%. 5

• Fluvoxamine increases duloxetine AUC by 460% and Cmax by 141%, reaching clinically significant levels. 5
• Smoking decreases duloxetine concentration by approximately 30%. 5
• CYP2D6 inhibitors increase duloxetine exposure to a lesser extent and do not require dose adjustment. 5

MAOI Interactions

Allow at least 14 days between discontinuing an MAOI and starting duloxetine; allow at least 5 days after stopping duloxetine before starting an MAOI. 1

• Do not start duloxetine in patients receiving linezolid or intravenous methylene blue due to serotonin syndrome risk. 1

Common Adverse Effects

• Nausea is the most common adverse effect and the primary reason for discontinuation; starting at 30 mg daily for 1 week significantly reduces nausea incidence. 2, 3, 4
• Other common adverse effects include dry mouth, headache, constipation, dizziness, fatigue, hyperhidrosis, and insomnia. 4
• Mild increases in blood pressure may occur; use caution in patients with hypertension. 3