What are the indications and dosing recommendations for Cymbalta (duloxetine)?

Indications and Dosing Recommendations for Cymbalta (Duloxetine)

Duloxetine (Cymbalta) is FDA-approved for major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain (including osteoarthritis pain and chronic low back pain), with specific dosing regimens for each indication.

FDA-Approved Indications

Major Depressive Disorder (MDD)

• Starting dose: 40 mg/day (given as 20 mg twice daily) to 60 mg/day (given either once daily or as 30 mg twice daily)
• Maintenance dose: 60 mg/day
• Maximum dose: 120 mg/day (though no additional benefit beyond 60 mg/day has been demonstrated) 1

Generalized Anxiety Disorder (GAD)

• Adults <65 years:
  • Starting dose: 60 mg once daily (may start at 30 mg once daily for 1 week to improve tolerability)
  • Maximum dose: 120 mg/day 1
• Geriatric patients:
  • Starting dose: 30 mg once daily for 2 weeks
  • Target dose: 60 mg/day
  • Maximum dose studied: 120 mg/day 1
• Pediatric patients (7-17 years):
  • Starting dose: 30 mg once daily for 2 weeks
  • Target dose: 30-60 mg once daily
  • Maximum dose studied: 120 mg/day 1, 2

Diabetic Peripheral Neuropathic Pain

• Dose: 60 mg once daily
• Note: No evidence that doses higher than 60 mg provide additional benefit
• For patients with tolerability concerns: Lower starting dose with gradual increase 1, 3

Fibromyalgia

• Starting dose: 30 mg once daily for 1 week
• Target dose: 60 mg once daily
• Note: No evidence that doses higher than 60 mg provide additional benefit 1, 4

Chronic Musculoskeletal Pain (Osteoarthritis and Low Back Pain)

• Starting dose: 30 mg once daily for 1 week
• Target dose: 60 mg once daily
• Note: No evidence that higher doses confer additional benefit 1, 4

Administration Guidelines

• Administer orally with or without food
• Swallow capsules whole - do not chew, crush, or open the capsule
• If a dose is missed, take it as soon as remembered unless it's almost time for the next dose 1

Efficacy Evidence

• Diabetic neuropathic pain: Duloxetine at 60 mg and 120 mg daily is effective with an NNT of 5 (95% CI 4 to 7) for ≥50% pain reduction 5
• Fibromyalgia: Effective at 60 mg daily with an NNT of 8 for ≥50% pain reduction 5, 4
• GAD: Significantly improves anxiety symptoms compared to placebo, with efficacy similar to other SSRIs and SNRIs 6
• MDD: Effective for core emotional symptoms and painful physical symptoms associated with depression 7

Special Populations and Dosing Considerations

Renal Impairment

• Severe renal impairment (GFR <30 mL/minute): Avoid use 1
• Moderate renal impairment: Consider lower starting dose with gradual titration 3, 1

Hepatic Impairment

• Chronic liver disease or cirrhosis: Avoid use 1
• Avoid duloxetine in patients with hepatic disease 3

Common Adverse Effects

• Nausea, dry mouth, headache, constipation, dizziness, fatigue, somnolence
• Diaphoresis, decreased appetite, weight loss
• Increased blood pressure and pulse 2, 1

Serious Adverse Effects (Uncommon)

• Suicidal thinking and behavior (through age 24 years)
• Behavioral activation/agitation
• Hypomania/mania
• Sexual dysfunction
• Seizures
• Abnormal bleeding
• Serotonin syndrome
• Hepatic failure (for duloxetine specifically) 2, 1

Discontinuation

• Gradual tapering recommended to prevent discontinuation symptoms
• Discontinuation symptoms may include: dizziness, headache, nausea, diarrhea, paresthesia, irritability, vomiting, insomnia, anxiety, hyperhidrosis, and fatigue 1

Important Drug Interactions

• Avoid concomitant use with potent CYP1A2 inhibitors
• Use with caution in patients receiving drugs extensively metabolized by CYP2D6 1

Duloxetine provides a versatile treatment option for multiple conditions, with the 60 mg once-daily dose being the most commonly recommended effective dose across indications, balancing efficacy and tolerability.