What are the on-label indications for duloxetine (Cymbalta)?

On-Label Indications for Duloxetine

Duloxetine is FDA-approved for five specific 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

Psychiatric Indications

• Major Depressive Disorder (MDD)

  • Approved for adults only
  • Effective dosage: 60 mg once daily (no evidence that doses greater than 60 mg/day provide additional benefits) 1
  • Demonstrated superiority over placebo in multiple randomized controlled trials

• Generalized Anxiety Disorder (GAD)

  • Approved for adults and pediatric patients 7 years and older
  • Effective dosage: 60-120 mg daily for adults 1
  • Demonstrated longer time to relapse compared to placebo

Pain Conditions

• Diabetic Peripheral Neuropathic Pain

  • Approved for adults only
  • Effective dosage: 60 mg daily 2, 1
  • SNRI mechanism provides effective analgesia at lower dosages than needed for depression 2

• Fibromyalgia

  • Approved for adults only
  • Effective dosage: 60 mg daily 2, 3, 1
  • Recommended as first-line or second-line treatment, particularly for patients with pain and depression, or pain and fatigue 3

• Chronic Musculoskeletal Pain

  • Approved for adults only
  • Includes conditions such as chronic low back pain and osteoarthritis pain 1

Clinical Considerations

Dosing Considerations

• Starting dose is typically 30 mg daily for 1-2 weeks before increasing to 60 mg daily to minimize side effects, particularly nausea 1, 4
• For most indications, 60 mg daily is the recommended therapeutic dose 1
• While 120 mg daily has shown efficacy in some conditions, there is limited evidence of additional benefit beyond 60 mg daily for most indications 1

Contraindications and Precautions

• Contraindicated in patients with:

  • Severe renal impairment (GFR <30 mL/min)
  • Chronic liver disease 3
  • Concomitant use with CYP1A2 inhibitors or nonselective, irreversible MAOIs 4

• Use with caution in:

  • Elderly patients (increased risk of CNS effects and falls)
  • Patients with cardiac disease (monitor for cardiovascular effects)
  • Patients taking CYP2D6 substrates with narrow therapeutic indices 3

Efficacy Evidence

• For diabetic neuropathy: Moderate-quality evidence supports efficacy at 60 mg and 120 mg daily doses 5
• For fibromyalgia: Lower quality evidence shows similar efficacy to diabetic neuropathy, with NNTB of 8 5
• For MDD: Multiple trials demonstrate superiority over placebo 1, 6
• For GAD: Demonstrated superiority over placebo in multiple trials 1, 6

Common Pitfalls

• Starting at full therapeutic dose (60 mg) rather than titrating from 30 mg can increase initial side effects, particularly nausea 4
• Using duloxetine in patients with severe renal impairment or hepatic disease can lead to increased adverse effects 3
• Failing to monitor for drug interactions, particularly with CYP1A2 inhibitors and CYP2D6 substrates 3, 4
• Abrupt discontinuation can lead to withdrawal symptoms; dose should be tapered gradually

Duloxetine's dual mechanism of action (inhibiting both serotonin and norepinephrine reuptake) makes it particularly useful for conditions with overlapping psychiatric and pain components, explaining its efficacy across multiple indications 6, 7.