Pharmacology · Serotonin-norepinephrine reuptake inhibitors (SNRIs)
Duloxetine !
An SNRI used for depression and anxiety and also for chronic pain: diabetic neuropathy, fibromyalgia and chronic musculoskeletal pain.
Updated 2026-11-01
The figure shows levomilnacipran, another SNRI, bound to human NET; no structure with duloxetine is available.
Mechanism of action
Duloxetine blocks the serotonin and norepinephrine transporters, raising both monoamines in the synapse. In the spinal cord, stronger descending serotonergic and noradrenergic pathways from the brainstem dampen pain signals, which is thought to explain its effect in neuropathic and chronic musculoskeletal pain.
- Duloxetine binds SERT and NET
- Serotonin and norepinephrine reuptake is blocked
- Descending pain-inhibiting pathways are strengthened
- Mood, anxiety and chronic pain improve over weeks
Pharmacokinetics
- Absorption
- Delayed-release (enteric-coated) capsule, so absorption starts later
- Metabolism
- In the liver by CYP1A2 and CYP2D6; duloxetine is a moderate CYP2D6 inhibitor
- Half-life
- About 12 hours (range 8 to 17)
Indications
- Major depressive disorder
- Generalised anxiety disorder
- Diabetic peripheral neuropathic pain
- Fibromyalgia
- Chronic musculoskeletal pain, including chronic low back pain Mechanical low back pain →
Adverse effects
Common
- Nausea, dry mouth, constipation
- Somnolence, fatigue, insomnia, dizziness
- Sweating and decreased appetite
- Sexual dysfunction
Contraindications
- MAO inhibitors for psychiatric use: not started within 5 days of stopping duloxetine, and duloxetine not started within 14 days of stopping an MAOI
- Starting duloxetine during linezolid or intravenous methylene blue
- Substantial alcohol use or chronic liver disease (label: not prescribed)
Key interactions
- Potent CYP1A2 inhibitors (fluvoxamine, some quinolone antibiotics)
- Much higher duloxetine levels; the combination is avoided
- CYP2D6 substrates with a narrow margin (tricyclics, phenothiazines, flecainide, propafenone)
- Higher levels of those drugs; thioridazine is not co-administered (ventricular arrhythmias)
- MAO inhibitors, triptans, tramadol, other serotonergic drugs
- Serotonin syndrome
- Alcohol
- Possible liver injury
- NSAIDs, aspirin, warfarin
- Higher bleeding risk
What is monitored
- Liver tests if symptoms of liver injury appear (jaundice, dark urine, right upper abdominal pain)
- Blood pressure, including orthostatic
- Mood and suicidal thoughts
- Sodium in older adults
Administration and safety
- Capsules are swallowed whole: not chewed, crushed or opened and sprinkled on food, because that can affect the enteric coating
- Not used with heavy alcohol intake
- Stopped by gradual tapering
Nursing care
- Ask about alcohol intake and liver disease before the first dose
- Teach the signs of liver injury and of low blood pressure on standing; fall precautions in older adults
- Check blood pressure at follow-up
- Assess suicidal thoughts early in treatment and after dose changes
- Teach that abrupt stopping causes dizziness, nausea and irritability
Pregnancy and breastfeeding
Used in pregnancy after weighing risks and benefits; exposure late in pregnancy is linked to neonatal adaptation problems and postpartum haemorrhage.
Test yourself
Think of the answer, then tap the question to see it.
Which antidepressant has approved indications for diabetic peripheral neuropathic pain, fibromyalgia and chronic musculoskeletal pain?
Duloxetine.
Why is duloxetine avoided in people with heavy alcohol use or chronic liver disease?
It can cause hepatotoxicity, including rare fatal liver failure, and alcohol may add to the liver injury.
Why should duloxetine capsules not be opened, crushed or sprinkled on food?
They are delayed-release capsules with an enteric coating; the label warns that breaking them can affect that coating.
Which antidepressant should not be combined with duloxetine because of CYP1A2 inhibition?
Fluvoxamine, a strong CYP1A2 inhibitor that markedly raises duloxetine levels.
Related drugs
Related conditions
← Back to the class: Serotonin-norepinephrine reuptake inhibitors (SNRIs)
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - DULOXETINE capsule, delayed release (DailyMed (U.S. National Library of Medicine), 2026); Duloxetine: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2025); 9KDM: Cryo-EM structure of LIPID-mediated human norepinephrine transporter NET in the presence of Levomilnacipran in an inward-open state at resolution of 2.46 angstrom. (RCSB Protein Data Bank, 2025).
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Representative model, for educational purposes only.