[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/) › Trazodone

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

# Trazodone

An antidepressant that blocks 5-HT2A receptors and weakly blocks serotonin reuptake. Very sedating, often used for sleep; can cause priapism.

Updated 2026-11-01

- Class: [Atypical antidepressants](https://durgical.com/en/pharmacology/classes/atypical-antidepressants/)
- Receptor: Serotonin 5-HT2A receptor (also SERT, alpha-1 and H1 receptors)
- ATC code: N06AX05

## Mechanism of action

Trazodone blocks 5-HT2A receptors and, more weakly, the serotonin transporter, and is a partial agonist at 5-HT1A receptors. It also blocks alpha-1 adrenergic and H1 receptors, explaining its sedation and orthostatic hypotension. Its metabolite m-chlorophenylpiperazine (mCPP) is also active.

- Trazodone blocks 5-HT2A receptors
- It weakly blocks serotonin reuptake
- H1 and alpha-1 block cause sleepiness and low blood pressure
- Mood and sleep improve

## Pharmacokinetics

**Absorption**
By mouth; tablets can be split along the score line but are not chewed or crushed

**Metabolism**
CYP3A4 forms the active metabolite mCPP; strong CYP3A4 inhibitors raise trazodone levels

## Indications

- Major depressive disorder
- Sometimes used for insomnia (off-label)

## Adverse effects

### Common

- Sleepiness and fatigue
- Dizziness and orthostatic hypotension
- Dry mouth, nausea
- Headache, blurred vision

### Serious (rare, important)

- Priapism (prolonged erection, an emergency)
- QT prolongation and arrhythmias, including torsades de pointes
- Orthostatic hypotension and syncope
- Suicidal thoughts and behaviour in young people (boxed warning)
- Serotonin syndrome
- Bleeding
- Hyponatraemia

## Contraindications

- MAO inhibitors, or within 14 days of stopping one; not started during linezolid or intravenous methylene blue
- Avoided with known QT prolongation or a history of arrhythmias

## Key interactions

**Strong CYP3A4 inhibitors (clarithromycin, itraconazole, voriconazole)**
Higher trazodone levels, more sedation and arrhythmia risk

**CYP3A4 inducers (rifampicin, carbamazepine, phenytoin, St John's wort)**
Lower trazodone levels

**Other QT-prolonging drugs (class IA and III antiarrhythmics, some antipsychotics)**
Additive arrhythmia risk

**Alcohol and other CNS depressants**
Additive sedation

**Other serotonergic drugs**
Serotonin syndrome

## What is monitored

- Orthostatic blood pressure and falls
- ECG with heart disease or other QT-prolonging drugs
- Mood and suicidal thoughts
- Sleepiness the next morning

## Administration and safety

- Given by mouth; drowsiness may lead to giving most of the daily amount at bedtime
- Tablets may be split on the score line; not chewed or crushed
- Stopped gradually

## Nursing care

- Teach men that an erection lasting more than four hours is an emergency that needs urgent care
- Check orthostatic blood pressure and teach to rise slowly; fall precautions in older adults
- Warn about drowsiness, driving and alcohol
- Assess suicidal thoughts early in treatment

## Pregnancy and breastfeeding

Decades of published human data have not identified a drug-related risk of major birth defects or miscarriage.

## Memory aid

TrazoDONE sleeping: sedation for sleep, but «trazoBONE» warns of priapism.

## Test yourself

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

## Which antidepressant is classically linked to priapism?

Trazodone. A prolonged erection can permanently damage erectile tissue and needs emergency care.

## Why is trazodone often used at night?

Its H1 and alpha-1 blockade causes marked sedation, which is why it is also used for insomnia.

## Why can clarithromycin increase the cardiac risk of trazodone?

Clarithromycin is a strong CYP3A4 inhibitor, so trazodone levels rise, and both drugs can prolong the QT interval.

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## Related drugs

- [Mirtazapine](https://durgical.com/en/pharmacology/mirtazapine/)
- [Bupropion](https://durgical.com/en/pharmacology/bupropion/)

[← 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 - TRAZODONE HYDROCHLORIDE tablet](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=71961ab1-951d-1493-f76c-2ff25cca2a85) (DailyMed (U.S. National Library of Medicine), 2026); [Trazodone: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a681038.html) (MedlinePlus (U.S. National Library of Medicine), 2025); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=N06AX) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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