Duloxetine
Cymbalta · Duloxetine Delayed-Release · Irenka
Serotonin-Norepinephrine Reuptake InhibitorGeneric availableTDM data
Although the exact mechanisms of the antidepressant, central pain inhibitory and anxiolytic actions of duloxetine in humans are unknown, these actions are believed to be related to its potentiation of serotonergic and noradrenergic activity in the CNS.
Compare Duloxetine →FDA-Approved Indications
- Major depressive disorder (adults)
- Generalized anxiety disorder (adults; pediatric 7+)
- Diabetic peripheral neuropathic pain (adults)
- Fibromyalgia (adults; pediatric 13+)
- Chronic musculoskeletal pain (adults)
Common Off-Label Uses
- Stress urinary incontinence
- Chemotherapy-induced neuropathy
What Sets This Drug Apart
- Broadest pain indication set of any antidepressant: FDA-approved for diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain in addition to MDD and GAD
- Most balanced SERT:NET ratio among SNRIs (~10:1) with potent noradrenergic reuptake from the starting dose — no dose threshold needed for dual action
- Hepatotoxicity warning in FDA label; avoid in substantial alcohol use or pre-existing liver disease; mandatory LFT monitoring
- Moderate CYP2D6 inhibitor — increases levels of CYP2D6 substrates (TCAs, some antipsychotics); also a CYP1A2 and CYP2D6 substrate
- Delayed-release capsule must be swallowed whole (enteric coating); cannot be opened, crushed, or given via feeding tube in standard form
- Hypertension risk present but possibly lower than venlafaxine; still requires baseline and periodic BP monitoring
Boxed Warning
SUICIDAL THOUGHTS AND BEHAVIORS