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

See also article: Introduction to Pharmacology

Pharmacokinetics of Duloxetine

Absorption
Distribution
Metabolism
Elimination
Half-life

See also article: Cytochrome (CYP) P450 Metabolism

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

Serotonin syndrome

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

See main article: Geriatric Pharmacology

Pediatric

See main article: Pediatric Pharmacology

Obstetric and Fetal

See main article: Obstetric and Fetal Pharmacology

Medically Ill

See main article: Psychotropic Dosing in the Medically Ill

Resources

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)

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