Pharmacology · Selective serotonin reuptake inhibitors (SSRIs)

Paroxetine !

An SSRI for depression, panic and social anxiety. It inhibits CYP2D6, and first-trimester use is linked to heart malformations in the baby.

Updated 2026-11-01

Class: Selective serotonin reuptake inhibitors (SSRIs)
Transporter: Serotonin transporter (SERT)
ATC code: N06AB05

Serotonin transporter (SERT)Paroxetine

The figure shows paroxetine bound at the central site of a thermostabilised human SERT (ts3).

Target in 3D: Serotonin transporter (SERT). PDB structure 5I6X (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

Paroxetine binds the central site of the serotonin transporter with high affinity and blocks serotonin reuptake. It also inhibits the liver enzyme CYP2D6 irreversibly, which explains many of its interactions, including loss of tamoxifen efficacy.

Paroxetine binds the central site of the serotonin transporter
Serotonin reuptake is blocked and serotonin acts longer
Over weeks, mood and anxiety improve
In the liver it inhibits CYP2D6, raising or blocking other drugs

Pharmacokinetics

Absorption: By mouth; immediate- and extended-release forms
Metabolism: Extensive in the liver through a saturable pathway; paroxetine inhibits CYP2D6 irreversibly
Half-life: About 15 to 20 hours after a single dose of the extended-release form

Indications

Major depressive disorder
Panic disorder
Social anxiety disorder
Premenstrual dysphoric disorder

Adverse effects

Common

Nausea, somnolence, dizziness
Sweating, tremor
Sexual dysfunction (ejaculatory disorders, low libido)
Dry mouth and constipation

Contraindications

MAO inhibitors, including linezolid and intravenous methylene blue, or within 14 days of stopping an MAOI
Drugs that prolong the QTc interval and are CYP2D6 substrates (such as thioridazine or pimozide)
Hypersensitivity to paroxetine

Key interactions

Tamoxifen: Less conversion of tamoxifen to its active metabolite through CYP2D6, so it may work less well; an antidepressant with little CYP2D6 inhibition is preferred
CYP2D6 substrates (tricyclics, some antipsychotics, some antiarrhythmics): Higher levels of those drugs
MAO inhibitors and other serotonergic drugs: Serotonin syndrome
NSAIDs, aspirin, warfarin: Higher bleeding risk

What is monitored

Mood and suicidal thoughts
Pregnancy status and plans in women of childbearing age
Bleeding with antithrombotic drugs
Symptoms when doses are missed or reduced

Administration and safety

Given by mouth; extended-release tablets are swallowed whole
Stopped by gradual tapering
The medicine list is checked for CYP2D6 substrates and tamoxifen before starting

Nursing care

Ask about pregnancy or plans to become pregnant, and report it to the prescriber
Check whether the person takes tamoxifen or other CYP2D6-dependent drugs
Assess suicidal thoughts early in treatment and after dose changes
Teach that abrupt stopping can cause dizziness, sensory disturbances and irritability

Pregnancy and breastfeeding

First-trimester exposure is linked in meta-analyses to a small rise in cardiovascular malformations; late exposure carries the neonatal risks of all SSRIs.

Test yourself

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

Why is paroxetine generally avoided in a woman planning pregnancy?

First-trimester exposure is associated with a higher rate of cardiovascular malformations in the baby.

Why can paroxetine make tamoxifen less effective?

Tamoxifen needs CYP2D6 to form its active metabolite, and paroxetine inhibits CYP2D6 irreversibly, so less active metabolite is made.

Which drugs are contraindicated with paroxetine because of QT risk?

Drugs that both prolong QT and are CYP2D6 substrates, such as thioridazine and pimozide, whose levels paroxetine raises.

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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 - PAROXETINE HYDROCHLORIDE tablet, film coated, extended release (DailyMed (U.S. National Library of Medicine), 2026); Paroxetine: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); 5I6X: X-ray structure of the ts3 human serotonin transporter complexed with paroxetine at the central site (RCSB Protein Data Bank, 2016).

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Representative model, for educational purposes only.