What are the indications and dosing guidelines for Duloxetine (Cymbalta)?

Duloxetine (Cymbalta): Indications and Dosing Guidelines

Duloxetine is FDA-approved for five major indications: major depressive disorder in adults, generalized anxiety disorder in adults and pediatric patients 7 years and older, diabetic peripheral neuropathic pain in adults, fibromyalgia in adults, and chronic musculoskeletal pain in adults. 1

FDA-Approved Indications

• Major Depressive Disorder (MDD): Recommended starting dose is 40-60 mg/day (given as 20 mg twice daily or 60 mg once daily). For some patients, starting at 30 mg once daily for 1 week before increasing to 60 mg once daily may improve tolerability. Maximum effective dose is 60 mg/day. 1

• Generalized Anxiety Disorder (GAD):

  • Adults <65 years: 60 mg once daily. May start at 30 mg once daily for 1 week before increasing. 1
  • Geriatric patients: 30 mg once daily for 2 weeks before considering increase to 60 mg/day. 1
  • Pediatric patients (7-17 years): 30 mg once daily for 2 weeks before considering increase to 60 mg once daily. Recommended range is 30-60 mg once daily. 1, 2

• Diabetic Peripheral Neuropathic Pain: 60 mg once daily. No evidence that higher doses provide additional benefit. For patients with tolerability concerns, a lower starting dose may be considered. 1, 3

• Fibromyalgia: 60 mg once daily. Begin at 30 mg once daily for 1 week before increasing to 60 mg once daily. No evidence that doses above 60 mg/day provide additional benefit. 1, 3

• Chronic Musculoskeletal Pain (including chronic low back pain and osteoarthritis pain): 60 mg once daily. Begin at 30 mg once daily for 1 week before increasing to 60 mg once daily. 2, 4

Administration Guidelines

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

Efficacy Evidence

• Diabetic Peripheral Neuropathy: Duloxetine 60 mg daily has demonstrated efficacy with a Number Needed to Treat (NNT) of 5 for achieving ≥50% pain reduction at 12 weeks. 5

• Fibromyalgia: Effective at 60 mg daily with an NNT of 8 for ≥50% pain reduction over 12 weeks. 5, 3

• Chronic Low Back Pain: Moderate-quality evidence demonstrates small improvements in chronic low back pain. 3

• Osteoarthritis Pain: Effective particularly in older patients (>65 years) and in patients with knee osteoarthritis. 3

Special Populations and Dosing Considerations

• Renal Impairment: Consider lower starting dosage and gradual increase for patients with renal impairment, especially for diabetic peripheral neuropathic pain. 1

• Hepatic Impairment: Use with caution; duloxetine is not recommended for patients with hepatic insufficiency. 6

• Elderly Patients: Start at lower doses (30 mg once daily) and titrate more slowly. 1

Common Adverse Effects

• Most common: nausea, dry mouth, headache, constipation, dizziness, and fatigue 2, 7
• Nausea occurs less frequently if treatment is initiated at 30 mg daily and titrated after one week to 60 mg daily 7
• Approximately 16% of patients discontinue treatment due to adverse effects 5

Drug Interactions

• CYP1A2 inhibitors (e.g., fluvoxamine): Can increase duloxetine exposure by up to 460%; concomitant use should be avoided 6

• CYP2D6 substrates: Duloxetine may increase exposure of drugs metabolized by CYP2D6 6

• Smoking: Associated with approximately 30% decrease in duloxetine concentration 6

• MAOIs: Do not use duloxetine with nonselective, irreversible monoamine oxidase inhibitors 7

Discontinuation

• Duloxetine should be tapered when discontinuing, especially after treatment longer than 3 weeks, to prevent withdrawal symptoms 2

Clinical Pearls

• For pain conditions, pain relief may begin within one week of treatment at the 60 mg daily dose 7
• When treating osteoarthritis pain, duloxetine is more effective in older patients (>65 years) than younger patients 3
• For diabetic neuropathy, duloxetine at 60 mg and 120 mg daily are efficacious, but 20 mg daily is not effective 8
• Duloxetine may be particularly beneficial for patients with comorbid pain and depression 3