[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Atypical antidepressants](https://durgical.com/en/pharmacology/classes/atypical-antidepressants/) › Nefazodone

# Nefazodone

## Atypical antidepressants?

Atypical antidepressants

A 5-HT2 antagonist antidepressant related to trazodone. A strong CYP3A4 inhibitor with a boxed warning for life-threatening liver failure.

Updated Nov 1, 2026

## Quick facts

**Group**
[Atypical antidepressants](https://durgical.com/en/pharmacology/classes/atypical-antidepressants/)

**Target**
Serotonin 5-HT2A receptor (antagonist); weak serotonin and noradrenaline reuptake inhibition

**Used for**
Major depressive disorder

**Key effects**
Drowsiness and difficulty concentrating · Dry mouth

**Monitor**
Liver tests · Mood and suicidal thoughts

**ATC**
N06AX06

No doses: the clinician sets them by the current guideline.

On this page

- The basics Mechanism of action
- Indications
- Adverse effects
- Pharmacokinetics
- Memory aid

- Safety Contraindications
- Key interactions
- What is monitored
- Administration and safety
- Pregnancy and breastfeeding
- Nursing care

- Study Test yourself

- Connections Connections

## Mechanism of action

Nefazodone is a phenylpiperazine that blocks central 5-HT2 receptors and inhibits the reuptake of serotonin and noradrenaline. It also blocks alpha-1 adrenergic receptors, which explains postural hypotension. It strongly inhibits CYP3A4, so it raises the levels of many drugs, and it can cause rare but fatal liver failure.

- Nefazodone blocks 5-HT2 receptors
- Weakly blocks serotonin and noradrenaline reuptake
- Alpha-1 block: dizziness on standing
- Strong CYP3A4 inhibition and rare liver failure

## Indications

- Major depressive disorder [Major depressive disorder →](https://durgical.com/en/conditions/major-depressive-disorder/)

## Adverse effects

### Common

- Drowsiness and difficulty concentrating
- Dry mouth, nausea, constipation
- Dizziness and light-headedness
- Weakness

### Serious (rare, important)

- Life-threatening hepatic failure (boxed warning)
- Suicidal thoughts in children, adolescents and young adults (boxed warning)
- Serotonin syndrome-like reactions with MAO inhibitors
- Priapism (rare reports)

## Contraindications

- Use with pimozide, carbamazepine, cisapride, terfenadine or astemizole
- Patients previously withdrawn from nefazodone because of liver injury
- Hypersensitivity to nefazodone or other phenylpiperazine antidepressants
- MAO inhibitors within the previous 14 days

## Key interactions

**Triazolam**
Much higher triazolam levels and sedation (CYP3A4 inhibition); the combination is avoided

**Pimozide and cisapride**
Higher levels, QT prolongation and torsades de pointes: contraindicated

**MAO inhibitors**
Serious, sometimes fatal reactions; 14 days are left after an MAOI and at least 7 days after nefazodone before an MAOI

## What is monitored

- Liver tests (AST, ALT) and signs of liver injury
- Mood and suicidal thoughts
- Blood pressure on standing

## Administration and safety

- Not started in active liver disease or with raised transaminases
- Stopped if signs of liver injury appear, and never restarted after liver injury

## Pregnancy and breastfeeding

Human data are limited; use weighs benefit and risk.

## Nursing care

- Teaches the patient to report yellow skin or eyes, dark urine, loss of appetite, nausea or malaise at once
- Reviews every other medicine for CYP3A4 interactions, especially benzodiazepines
- Watches for drowsiness and dizziness on standing
- Asks about mood and suicidal thoughts

## Pharmacokinetics

**Absorption**
By mouth, with low and variable bioavailability (about 20%)

**Metabolism**
Extensive liver metabolism, with active metabolites

**Half-life**
Short: 2 to 4 hours for the parent drug

## Memory aid

«NefazoDONE with the liver»: think Liver failure, 3A4 inhibition and trazodone's relative.

## Test yourself

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

## What is the boxed warning unique to nefazodone among antidepressants?

Life-threatening hepatic failure.

## Why is nefazodone contraindicated with pimozide?

It strongly inhibits CYP3A4, raising pimozide levels and the risk of QT prolongation and torsades.

## Which receptor block explains postural hypotension with nefazodone?

Alpha-1 adrenergic blockade.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/pharmacology/nefazodone/)

[More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology)

## Connections

## Related drugs 2

- [Trazodone](https://durgical.com/en/pharmacology/trazodone/)
- [Pimozide](https://durgical.com/en/pharmacology/pimozide/)

## Related conditions 1

- [Major depressive disorder](https://durgical.com/en/conditions/major-depressive-disorder/)

[← Back to the class: Atypical antidepressants](https://durgical.com/en/pharmacology/classes/atypical-antidepressants/)

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 - NEFAZODONE HYDROCHLORIDE tablet](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51ff7db5-aaf9-4c3c-86e6-958ebf16b60f) (DailyMed (U.S. National Library of Medicine), 2026); [Nefazodone: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a695005.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=N06AX06) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.

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