Duloxetine (Cymbalta)

Pharmacokinetics of Duloxetine

Duloxetine: Cytochrome P450 Metabolism

Substrate of (Metabolized by) 1A2
  • Major depressive disorder
  • Diabetic peripheral neuropathy
  • Neuropathic pain
    • Duloxetine is one of two antidepressants that treats neuropathic pain (other is amitriptyline).[1]
    • The noradrengergic effects from duloxetine are thought to modulate pain pathways, hence why duloxetine is used for neuropathic pain.

Dosing for Duloxetine

Starting 30 mg PO daily
Titration Increase by 30 mg every 1-2 weeks
Maximum 120 mg PO daily
Taper Tapering/Switching Antidepressants
  • Duloxetine comes in oral formulation.
  • Individuals with pre-existing liver disease or alcohol use are at a greater risk of duloxetine-induced liver injury.[2][3][4]
    • The FDA has reported cases of hepatitis with abdominal pain, hepatomegaly, and elevation of transaminase levels (AST, ALT) to more than twenty times the upper limit of normal with or without jaundice, reflecting a mixed or hepatocellular pattern of liver injury.[5]
  • Duloxetine is relatively more anticholinergic than other SNRIs (e.g. - it is negligible in venlafaxine/desvenlafaxine)
  • Duloxetine also has a Health Canada approval for treatment of diabetic peripheral neuropathy
  • Duloxetine is much less activating than other SNRIs such as venlafaxine/desvenlafaxine
  • Duloxetine may even cause sedation for some individuals
  • The discontinuation/withdrawal syndrome from duloxetine can be quite challenging