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# Venlafaxine

An SNRI antidepressant that blocks serotonin and norepinephrine reuptake. It can raise blood pressure and causes a marked withdrawal if stopped suddenly.

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: N06AX16

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

ⓘ The figure shows paroxetine at the central site of human SERT, the same site venlafaxine blocks; no structure with venlafaxine is available.

**Target in 3D:** Serotonin transporter (SERT) and norepinephrine transporter (NET). 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

Venlafaxine and its active metabolite O-desmethylvenlafaxine (desvenlafaxine) block the serotonin transporter and the norepinephrine transporter, and weakly the dopamine transporter. They have no meaningful affinity for muscarinic, H1 or alpha-1 receptors, so they lack the anticholinergic and sedative effects of tricyclics.

- Venlafaxine and desvenlafaxine bind SERT and NET
- Reuptake of serotonin and norepinephrine is blocked
- Both monoamines act longer in the synapse
- Mood and anxiety improve over weeks; blood pressure can rise

## Pharmacokinetics

**Absorption**
Well absorbed by mouth; extensive first pass in the liver; food does not change it

**Metabolism**
Converted by CYP2D6 to O-desmethylvenlafaxine (ODV), also active

**Elimination**
Mainly by the kidneys as metabolites; clearance varies widely in kidney impairment

**Half-life**
Short: about 5 hours for venlafaxine and 11 hours for ODV

## Indications

- Major depressive disorder
- Generalised anxiety disorder
- Social anxiety disorder and panic disorder
- Sometimes used for menopausal hot flushes (off-label)

## Adverse effects

### Common

- Nausea, dry mouth, constipation
- Sweating
- Insomnia or somnolence, dizziness
- Sexual dysfunction (abnormal ejaculation, low libido)

### Serious (rare, important)

- Suicidal thoughts and behaviour in young people (boxed warning)
- Sustained rise in blood pressure (dose-related)
- Serotonin syndrome
- Marked discontinuation syndrome
- Bleeding
- Hyponatraemia
- Seizures
- Angle-closure glaucoma
- Interstitial lung disease and eosinophilic pneumonia (rare)

## Contraindications

- MAO inhibitors, including linezolid and intravenous methylene blue, or within 14 days of stopping an MAOI
- Hypersensitivity to venlafaxine or desvenlafaxine

## Key interactions

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

**Strong CYP2D6 inhibitors**
More venlafaxine and less ODV

**CYP3A inhibitors**
Higher venlafaxine and ODV levels and more toxicity

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

## What is monitored

- Blood pressure before starting and regularly during treatment
- Mood and suicidal thoughts
- Sodium in older adults
- Symptoms when doses are missed or reduced

## Administration and safety

- Extended-release capsules are swallowed whole: not divided, crushed, chewed or dissolved
- Taken with food, as the label directs; missed doses matter because withdrawal appears quickly
- Stopped by gradual tapering

## Nursing care

- Measure blood pressure at baseline and at follow-up visits
- Teach that missed doses or abrupt stopping can cause dizziness, «brain zaps», nausea and irritability within a day or so
- Assess suicidal thoughts early in treatment and after dose changes
- Teach the signs of serotonin syndrome and of bleeding

## Pregnancy and breastfeeding

Used in pregnancy after weighing risks and benefits; exposure late in pregnancy is linked to neonatal adaptation problems, and SNRIs are linked to postpartum haemorrhage.

## Memory aid

VENlafaxine VENts pressure upward: watch blood pressure, and never stop it suddenly.

## Test yourself

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

## Which adverse effect of venlafaxine requires blood pressure checks, and why does it happen?

A dose-related, sometimes sustained rise in blood pressure, because blocking norepinephrine reuptake increases sympathetic tone.

## Why does venlafaxine cause a more marked discontinuation syndrome than fluoxetine?

Venlafaxine and ODV have short half-lives, so levels fall within hours of a missed dose; fluoxetine and norfluoxetine take weeks.

## What is the active metabolite of venlafaxine, and which enzyme makes it?

O-desmethylvenlafaxine (desvenlafaxine), formed by CYP2D6.

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## Related drugs

- [Duloxetine](https://durgical.com/en/pharmacology/duloxetine/)

[← 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 - VENLAFAXINE HYDROCHLORIDE capsule, extended release](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3e51f786-3691-4ec4-836b-7f2c9a385aa7) (DailyMed (U.S. National Library of Medicine), 2026); [Venlafaxine: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a694020.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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Representative model, for educational purposes only.

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