What is the recommended dose of Cymbalta (duloxetine) for an adult patient with depression, anxiety, or chronic pain?

Cymbalta (Duloxetine) Dosing Recommendations

For adult patients with depression, anxiety, or chronic pain, start Cymbalta at 30 mg once daily for one week, then increase to the target dose of 60 mg once daily, which is the most effective and well-tolerated dose across all indications. 1

Indication-Specific Dosing

Major Depressive Disorder

• Start at 40 mg/day (20 mg twice daily) or 60 mg/day (once daily or 30 mg twice daily) 1
• For patients who need gradual adjustment, begin with 30 mg once daily for 1 week before increasing to 60 mg once daily 1
• Target dose: 60 mg once daily - doses above 60 mg/day provide no additional benefit despite being studied up to 120 mg/day 1, 2

Generalized Anxiety Disorder

• Adults <65 years: Start at 60 mg once daily 1
• For tolerability concerns, start at 30 mg once daily for 1 week, then increase to 60 mg once daily 1
• Geriatric patients (≥65 years): Start at 30 mg once daily for 2 weeks before increasing to 60 mg once daily 1
• Maximum studied dose is 120 mg/day, but no evidence supports doses above 60 mg/day 1, 3

Chronic Pain Conditions

Diabetic Peripheral Neuropathic Pain

• Administer 60 mg once daily 1
• For tolerability concerns, consider starting lower 1
• No benefit from doses higher than 60 mg/day, and higher doses are less well tolerated 1, 4
• In patients with renal impairment (common in diabetes), use lower starting dose with gradual titration 1

Fibromyalgia

• Start at 30 mg once daily for 1 week, then increase to 60 mg once daily 1
• Target dose: 60 mg once daily 1
• Some patients respond to the 30 mg starting dose 1
• Doses above 60 mg/day provide no additional benefit and increase adverse reactions 1, 5, 4

Chronic Musculoskeletal Pain (including osteoarthritis and low back pain)

• Start at 30 mg once daily for 1 week, then increase to 60 mg once daily 1
• Target dose: 60 mg once daily 1
• Higher doses offer no additional benefit and increase adverse reactions 1, 4

Neuropathic Pain (General)

• Starting dose: 30-60 mg daily; increase to 60-120 mg daily 5
• Duloxetine is recommended as a first-line coanalgesic for neuropathic pain 5
• FDA-approved for diabetic peripheral neuropathy at 60 mg once daily 5

Critical Dosing Strategy for Tolerability

The Mayo Clinic approach is optimal: start at 30 mg once daily for 1 week before increasing to 60 mg once daily to reduce nausea, with only transitory impact on effectiveness during the first week 6. This strategy is particularly important because:

• Nausea is the most common adverse event and the primary reason for discontinuation 3, 7
• Starting at 30 mg significantly reduces nausea without compromising long-term efficacy 7
• Pain relief can occur within one week at the 60 mg dose 7

Special Populations

Geriatric Patients

• For GAD: Start at 30 mg once daily for 2 weeks, then increase to 60 mg once daily 1
• Use slower titration due to increased sensitivity 5

Hepatic Impairment

• Avoid use in patients with chronic liver disease or cirrhosis 1

Renal Impairment

• Avoid use in severe renal impairment (GFR <30 mL/min) 1
• For diabetic patients with renal disease: use lower starting dose with gradual titration 1

Evidence Quality and Ranking

Duloxetine is the only antidepressant with high-certainty evidence for chronic pain management 8. A 2023 Cochrane network meta-analysis of 176 studies (28,664 participants) found:

• Duloxetine at standard dose (60 mg) showed small to moderate effects for substantial pain relief (OR 1.91,95% CI 1.69-2.17) 8
• Standard dose (60 mg) was equally efficacious as high dose across all outcomes 8
• Moderate-certainty evidence supports duloxetine for pain intensity, physical function, sleep, quality of life, and patient global impression of change 8

Discontinuation Protocol

Never stop abruptly - gradual dose reduction is essential to prevent discontinuation syndrome 1. Discontinuation symptoms include:

• Dizziness, headache, nausea, diarrhea 1
• Paresthesia, irritability, vomiting, insomnia 1
• Anxiety, hyperhidrosis, fatigue 1

Common Pitfalls to Avoid

• Do not start at 60 mg in patients concerned about tolerability - the 30 mg starting dose for one week significantly reduces nausea 6, 7
• Do not exceed 60 mg/day expecting better results - no evidence supports additional benefit, and adverse events increase 1, 8
• Do not use in combination with CYP1A2 inhibitors 7
• Do not combine with MAOIs - allow 14 days between MAOI discontinuation and duloxetine initiation, and 5 days between duloxetine discontinuation and MAOI initiation 1