What is the maximum recommended dose of duloxetine (Cymbalta)?

Maximum Recommended Dose of Duloxetine

The maximum recommended dose of duloxetine is 120 mg per day, although there is no evidence that doses greater than 60 mg per day confer additional benefits in most indications. 1

Dosing Guidelines by Indication

• For Major Depressive Disorder (MDD):

  • Starting dose: 40-60 mg/day (given as 20 mg twice daily or 60 mg once daily) 1
  • While 120 mg/day was shown to be effective, there is no evidence that doses greater than 60 mg/day provide additional benefits 1

• For Generalized Anxiety Disorder (GAD):

  • Adults under 65: 60 mg once daily (initial dose) 1
  • While 120 mg once daily was shown to be effective, there is no evidence that doses greater than 60 mg/day provide additional benefits 1
  • If increasing beyond 60 mg, do so in increments of 30 mg once daily 1
  • Maximum studied dose: 120 mg per day 1

• For Diabetic Peripheral Neuropathic Pain:

  • Recommended dose: 60 mg once daily 1
  • No evidence that doses higher than 60 mg once daily confer additional significant benefit 1
  • Higher dosages are clearly less well tolerated 1

• For Fibromyalgia:

  • Recommended dose: 60 mg once daily 1
  • No evidence that dosages greater than 60 mg/day confer additional benefit 1
  • Higher dosages were associated with a higher rate of adverse reactions 1

Improving Tolerability

• Starting at a lower dose (30 mg daily) for 1 week before increasing to 60 mg may improve tolerability 2, 1
• The most common adverse effect is nausea, which can be reduced by this gradual titration approach 2, 3
• For patients with renal insufficiency, consider a lower starting dose and gradual titration 4, 1

Safety Considerations

• Duloxetine is generally well tolerated with few reported serious side effects 3, 5
• Common adverse events are mainly gastrointestinal and nervous system related 5
• Unlike tricyclic antidepressants, duloxetine does not have the same cardiac toxicity concerns 2
• Duloxetine is contraindicated in patients with severe hepatic and renal impairment 2
• Serious adverse events are rare, even with long-term use 6

Efficacy at Different Doses

• For diabetic peripheral neuropathy, 60 mg and 120 mg daily are efficacious, but lower daily doses are not 7
• In fibromyalgia, similar doses (60-120 mg) are effective with similar magnitude of effect 7
• Higher doses (120 mg) are associated with more adverse effects in a dose-dependent manner 7

Clinical Pearls

• Duloxetine does not typically produce clinically important electrocardiographic or blood pressure changes 2, 4
• The studied dose range extends up to 400 mg/day, but the maximum approved dose is 120 mg/day 5
• In long-term studies, duloxetine has demonstrated consistent safety profiles with no new safety signals emerging 6
• Pregabalin, duloxetine, or gabapentin are recommended as initial pharmacologic treatments for neuropathic pain in diabetes 8