[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Serotonin-norepinephrine reuptake inhibitors (SNRIs)](https://durgical.com/en/pharmacology/classes/serotonin-norepinephrine-reuptake-inhibitors/) › Duloxetine

[Pharmacology](https://durgical.com/en/pharmacology/) · [Serotonin-norepinephrine reuptake inhibitors (SNRIs)](https://durgical.com/en/pharmacology/classes/serotonin-norepinephrine-reuptake-inhibitors/)

# Duloxetine

An SNRI used for depression and anxiety and also for chronic pain: diabetic neuropathy, fibromyalgia and chronic musculoskeletal pain.

Updated 2026-11-01

- Class: [Serotonin-norepinephrine reuptake inhibitors (SNRIs)](https://durgical.com/en/pharmacology/classes/serotonin-norepinephrine-reuptake-inhibitors/)
- Transporter: Serotonin transporter (SERT) and norepinephrine transporter (NET)
- ATC code: N06AX21

⇄**Serotonin transporter (SERT) and norepinephrine transporter (NET)**Duloxetine

ⓘ The figure shows levomilnacipran, another SNRI, bound to human NET; no structure with duloxetine is available.

**Target in 3D:** Serotonin transporter (SERT) and norepinephrine transporter (NET). PDB structure 9KDM (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/9KDM) · Drag to rotate · pinch to zoom

## 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 →](https://durgical.com/en/conditions/mechanical-low-back-pain/)

## Adverse effects

### Common

- Nausea, dry mouth, constipation
- Somnolence, fatigue, insomnia, dizziness
- Sweating and decreased appetite
- Sexual dysfunction

### Serious (rare, important)

- Suicidal thoughts and behaviour in young people (boxed warning)
- Hepatotoxicity, occasionally fatal liver failure
- Orthostatic hypotension, falls and syncope
- Serotonin syndrome
- Bleeding
- Severe skin reactions
- Rise in blood pressure
- Urinary hesitation and retention
- Hyponatraemia

## 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.

## Memory aid

DULoxetine DULls pain: depression, anxiety, diabetic nerve pain, fibromyalgia and the aching back, but spare the liver.

## 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.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/pharmacology/duloxetine/)

## Related drugs

- [Venlafaxine](https://durgical.com/en/pharmacology/venlafaxine/)
- [Amitriptyline](https://durgical.com/en/pharmacology/amitriptyline/)

## Related conditions

- [Mechanical low back pain](https://durgical.com/en/conditions/mechanical-low-back-pain/)

[← Back to the class: Serotonin-norepinephrine reuptake inhibitors (SNRIs)](https://durgical.com/en/pharmacology/classes/serotonin-norepinephrine-reuptake-inhibitors/)

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](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fb37745f-fb40-4f7f-8143-ea1874c38e1b) (DailyMed (U.S. National Library of Medicine), 2026); [Duloxetine: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a604030.html) (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.](https://www.rcsb.org/structure/9KDM) (RCSB Protein Data Bank, 2025).

## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake

Representative model, for educational purposes only.

---
Source: https://durgical.com/en/pharmacology/duloxetine/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/duloxetine/