[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Selective serotonin reuptake inhibitors (SSRIs)](https://durgical.com/en/pharmacology/classes/selective-serotonin-reuptake-inhibitors/) › Fluoxetine

[Pharmacology](https://durgical.com/en/pharmacology/) · [Selective serotonin reuptake inhibitors (SSRIs)](https://durgical.com/en/pharmacology/classes/selective-serotonin-reuptake-inhibitors/)

# Fluoxetine

The classic SSRI antidepressant, on the WHO essential list. It and its active metabolite last for weeks, so it is slow to leave the body.

Updated 2026-11-01

- Class: [Selective serotonin reuptake inhibitors (SSRIs)](https://durgical.com/en/pharmacology/classes/selective-serotonin-reuptake-inhibitors/)
- Transporter: Serotonin transporter (SERT)
- ATC code: N06AB03
- WHO Model List of Essential Medicines

⇄**Serotonin transporter (SERT)**Fluoxetine

ⓘ The figure shows paroxetine, another SSRI that occupies the same central site of human SERT; no human SERT structure with fluoxetine is available.

**Target in 3D:** Serotonin transporter (SERT). PDB structure 5I6X (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/5I6X) · Drag to rotate · pinch to zoom

## Mechanism of action

Fluoxetine blocks the serotonin transporter on the presynaptic neuron, so serotonin released into the synapse is taken back more slowly and acts longer. Its active metabolite norfluoxetine does the same. The mood effect appears over weeks, as serotonin receptors and circuits adapt.

- Fluoxetine binds the central site of the serotonin transporter
- Serotonin reuptake into the presynaptic neuron is blocked
- Serotonin stays longer in the synapse
- Over weeks, receptors adapt and mood and anxiety improve

## Pharmacokinetics

**Absorption**
Well absorbed by mouth, with or without food

**Metabolism**
In the liver to norfluoxetine, also active; fluoxetine is a potent inhibitor of CYP2D6

**Half-life**
Long: 4 to 6 days for fluoxetine with chronic use and 4 to 16 days for norfluoxetine, so dose changes take weeks to show in plasma

**Onset and duration**
The antidepressant effect builds over several weeks

## Indications

- Major depressive disorder
- Obsessive-compulsive disorder
- Bulimia nervosa (binge eating and vomiting)
- Panic disorder

## Adverse effects

### Common

- Nausea, diarrhoea, loss of appetite
- Insomnia, anxiety and nervousness, especially early on
- Sexual dysfunction (low libido, delayed orgasm)
- Tremor, sweating, headache

### Serious (rare, important)

- Suicidal thoughts and behaviour in children, adolescents and young adults (boxed warning)
- Serotonin syndrome
- Hyponatraemia (SIADH)
- Bleeding, especially with NSAIDs, aspirin or warfarin
- Switch to mania in bipolar disorder
- QT prolongation

## Contraindications

- MAO inhibitors for psychiatric use: not started within 5 weeks of stopping fluoxetine, and fluoxetine not started within 14 days of stopping an MAOI
- Starting fluoxetine during treatment with linezolid or intravenous methylene blue
- Pimozide or thioridazine (QT prolongation and higher levels of these drugs)

## Key interactions

**MAO inhibitors, linezolid, triptans, tramadol, fentanyl, lithium, St John's wort**
Serotonin syndrome

**Drugs metabolised by CYP2D6 (tricyclics, some antipsychotics, flecainide)**
Much higher levels of those drugs, because fluoxetine inhibits CYP2D6

**NSAIDs, aspirin, warfarin**
Higher bleeding risk

**Other drugs that prolong the QT interval**
Additive risk of arrhythmia

## What is monitored

- Mood, suicidal thoughts and unusual behaviour, especially in the first months and after dose changes
- Signs of mania or hypomania
- Sodium in older adults or people on diuretics
- Weight and appetite

## Administration and safety

- Given by mouth; food does not matter for absorption
- Because of the very long half-life, effects of a change and interactions persist for weeks
- Switching to an MAOI needs the long washout set on the label

## Nursing care

- Ask about and record suicidal thoughts at the start and at each dose change; families watch for agitation, insomnia or new impulsiveness
- Explain that improvement takes weeks and that the medicine is not stopped suddenly without the prescriber
- Teach the signs of serotonin syndrome: agitation, sweating, tremor, muscle jerks, fever
- Check for bleeding or bruising when NSAIDs, aspirin or anticoagulants are also used
- Watch for confusion or falls in older adults (low sodium)

## Pregnancy and breastfeeding

Used in pregnancy after weighing risks and benefits; SSRI exposure late in pregnancy is linked to persistent pulmonary hypertension and poor adaptation in the newborn.

## Memory aid

FLUoxetine FLows out slowly: weeks to go, so it is the SSRI least likely to cause withdrawal and the slowest to wash out before an MAOI.

## Test yourself

Think of the answer, then tap the question to see it.

## Why must a person wait longer after stopping fluoxetine than after other SSRIs before starting an MAOI?

Fluoxetine and norfluoxetine have very long half-lives, so serotonergic activity persists for weeks. The label sets a longer interval (5 weeks) to avoid serotonin syndrome.

## Why is fluoxetine the SSRI least likely to cause a discontinuation syndrome?

Its long half-life and active metabolite mean levels fall slowly, acting as a built-in taper.

## A patient on a tricyclic starts fluoxetine and develops tricyclic toxicity. Why?

Fluoxetine is a potent CYP2D6 inhibitor, and CYP2D6 metabolises tricyclics, so their levels rise.

## Which eating disorder is an approved indication for fluoxetine?

Bulimia nervosa (binge eating and vomiting behaviours).

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

## Related drugs

- [Sertraline](https://durgical.com/en/pharmacology/sertraline/)
- [Escitalopram](https://durgical.com/en/pharmacology/escitalopram/)

[← Back to the class: Selective serotonin reuptake inhibitors (SSRIs)](https://durgical.com/en/pharmacology/classes/selective-serotonin-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 - FLUOXETINE capsule](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6f4e4e9f-9ded-452f-b3ef-ab6aa9c72952) (DailyMed (U.S. National Library of Medicine), 2026); [Fluoxetine: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a689006.html) (MedlinePlus (U.S. National Library of Medicine), 2025); [eEML - Electronic Essential Medicines List](https://list.essentialmeds.org/?query=fluoxetine) (World Health Organization, 2025); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=N06AB) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.

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