Pharmacology · Serotonin-norepinephrine reuptake inhibitors (SNRIs)
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
The figure shows paroxetine at the central site of human SERT, the same site venlafaxine blocks; no structure with venlafaxine is available.
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)
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.
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.
Related drugs
← Back to the class: Serotonin-norepinephrine reuptake inhibitors (SNRIs)
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 (DailyMed (U.S. National Library of Medicine), 2026); Venlafaxine: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2025); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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.