Duloxetine
Duloxetine is a serotonin-norepinephrine reuptake inhibitor (SNRI) approved for depression, generalised anxiety, diabetic peripheral neuropathic pain and chronic musculoskeletal pain. It is widely used as a first-line option when both mood and pain are concerns.
- Chemical formula
- C18H19NOS
- CAS number
- 116539-59-4
- ATC code
- N06AX21
- Molecular weight
- 297.41 g/mol
- Drug class
- Serotonin-norepinephrine reuptake inhibitor (SNRI)
- Also known as
- Cymbalta, Yentreve
What is it?
Duloxetine is a serotonin-norepinephrine reuptake inhibitor (SNRI) approved by the FDA in 2004, marketed primarily as Cymbalta by Eli Lilly. It is on the WHO Essential Medicines List and is widely available as authorised generic. The molecule occupies a useful niche where mood and pain symptoms overlap, since SNRIs treat both via the same mechanism more effectively than SSRIs.
Mechanism of action
Duloxetine inhibits the reuptake of both serotonin and norepinephrine at the synapse, with weaker effect on dopamine. The dual monoamine action distinguishes it from SSRIs and contributes to its analgesic effect in neuropathic and musculoskeletal pain — a property thought to reflect descending pain modulation pathways in the spinal cord. Antidepressant effect develops over weeks; pain relief can appear within 1–2 weeks.
Pharmacokinetics
Duloxetine is well absorbed after oral administration with bioavailability of approximately 50%. Peak plasma levels occur 6 hours post-dose. The terminal half-life is about 12 hours, supporting once or twice daily dosing. Hepatic metabolism is via CYP1A2 and CYP2D6 with multiple metabolites. Steady state is reached within several days. Excretion is primarily renal as metabolites.
Indications
Duloxetine is approved for major depressive disorder, generalised anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia, chronic musculoskeletal pain (back pain, osteoarthritis) and stress urinary incontinence (in some regions, marketed as Yentreve). It is generally considered first-line for depression with comorbid pain or for chronic pain syndromes where antidepressant pain modulation is preferred.
Safety profile
Common adverse effects include nausea (most prominent in the first 1–2 weeks), dry mouth, headache, fatigue, sleep disturbance and sexual dysfunction. Serious risks include hepatotoxicity (warnings about heavy alcohol use and pre-existing liver disease), serotonin syndrome with co-administered serotonergic agents, and SNRI discontinuation syndrome on abrupt cessation. Mild blood pressure increase can occur.
Products containing this ingredient
Frequently asked questions
How is duloxetine different from an SSRI? ▾
Duloxetine is an SNRI — it inhibits reuptake of both serotonin and norepinephrine, while SSRIs target only serotonin. The dual action gives it an analgesic effect on neuropathic and musculoskeletal pain that SSRIs largely lack, making it preferred when depression and pain coexist. According to clinical guidelines, it is first-line for fibromyalgia and diabetic neuropathy.
How long does duloxetine take to work? ▾
For depression and anxiety, partial response within 2 weeks and fuller response over 4–6 weeks. For pain indications (neuropathic, fibromyalgia), pain relief typically appears within 1–2 weeks even before mood improves. The medication should not be judged ineffective before 4–6 weeks at an adequate dose.
Can duloxetine cause liver problems? ▾
Duloxetine carries a label warning about hepatotoxicity, particularly with heavy alcohol use, pre-existing liver disease or hepatic impairment. According to the prescribing information, baseline and periodic liver function tests are reasonable in users with risk factors, and persistent jaundice or new abdominal pain warrants prompt evaluation.
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