Duloxetine (Cymbalta)

Primer

Duloxetine (Trade name: Cymbalta) is an antidepressant in the serotonin norepinephrine reuptake inhibitor (SNRI) class used in the treatment of major depressive disorder and neuropathic pain..

Pharmacokinetics

Pharmacokinetics of Duloxetine

Absorption
Distribution
Metabolism
Elimination
Half-life

Duloxetine: Cytochrome P450 Metabolism

Substrate of (Metabolized by) 1A2
Induces
Inhibits

Pharmacodynamics

Mechanism of Action

Toxicity

Indications

  • 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

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

Formulations

  • Duloxetine comes in oral formulation.

Monitoring

Contraindications

Absolute

Relative

  • 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]

Drug-Drug Interactions

Side Effects

  • Duloxetine is relatively more anticholinergic than other SNRIs (e.g. - it is negligible in venlafaxine/desvenlafaxine)

Adverse Events

Clinical Pearls

  • 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

Special Populations

Geriatric

Pediatric

Obstetric and Fetal

Medically Ill

Resources

References

1) Lunn, M. P., Hughes, R. A., & Wiffen, P. J. (2014). Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. The Cochrane database of systematic reviews, (1), CD007115.
2) Kang, S. G., Park, Y. M., Lee, H. J., & Yoon, B. (2011). Duloxetine-induced liver injury in patients with major depressive disorder. Psychiatry investigation, 8(3), 269.
3) FDA Drug Monograph: Cymbalta (duloxetine)
4) McIntyre, R. S., Panjwani, Z. D., Nguyen, H. T., Woldeyohannes, H. O., Alsuwaidan, M., Soczynska, J. K., ... & Kennedy, S. H. (2008). The hepatic safety profile of duloxetine: a review. Expert opinion on drug metabolism & toxicology, 4(3), 281-285.
5) FDA Drug Monograph: Cymbalta (duloxetine)