Paroxetine

PAXIL

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Pronunciation: pa-ROX-e-teen (PAX-il)

Paroxetine ballicule: receptor binding, kinetics and half-life diagram — Mechanism of action: Paroxetine ballicule

Paroxetine PAXIL mascot mnemonic cartoon — Visual mnemonic: Paroxetine mascot
**“Pear rocks a teen (Paxil Rose)”**
Crimson roses → antimuscarinic effects

What it isSerotonin reuptake inhibitor with antimuscarinic and weaker norepinephrine effects; depression and anxiety disorders.

Why this oneAmong SSRIs it is the most anticholinergic, most sedating and most prone to weight gain; it also treats menopausal hot flashes.

What limits itShort persistence causes withdrawal; CYP2D6 inhibition compromises tamoxifen and raises many substrates. Avoid in pregnancy when possible.

Pearls

First-trimester exposure linked to cardiac malformations.
Low-dose mesylate salt (7.5 mg) is labeled for hot flashes.

Paroxetine molecular structure (skeletal formula) — Molecular structure: Paroxetine

Paroxetine prescription history

Animated chart of estimated U.S. prescriptions per year, Antidepressants (1957–2026). Paroxetine enters in 1992 (estimated).

FDA-approved for

depression (1992)
OCD (1996)
panic disorder (1996)
social anxiety disorder (1999)
GAD (2001)
PTSD (2001)
PMDD (2002)
menopausal hot flashes (2013)

Off-label

premature ejaculation

Classes and tags

Clinical profile

Therapeutic safety burden2 / 4

Overdose danger2 / 4

Weight-gain liability2 / 4

Sedation liability1 / 4

QT / Torsades0 / 4

Direct muscarinic antagonism2 / 4

Embryofetal risk3 / 4

Legacy pregnancy categoryD

Defining liabilityAnticholinergic burden, sexual dysfunction, withdrawal and strong CYP2D6 inhibition.

FDA label

Read the full label on DailyMed ↗

BOXED WARNING Increased risk of suicidal thoughts and behaviors in pediatric and young adult patients; monitor closely. Not approved for pediatric use.

FDA dosing	Population	Start	Target	Max
Major depressive disorder (MDD)	Adults	20 mg QD	20 mg QD	50 mg QD
Obsessive-compulsive disorder (OCD)	Adults	20 mg QD	40 mg QD	60 mg QD
Panic disorder (PD)	Adults	10 mg QD	40 mg QD	60 mg QD
Posttraumatic stress disorder (PTSD)	Adults	20 mg QD	20 mg QD	50 mg QD
Social anxiety disorder (SAD)	Adults	20 mg QD	20 mg QD	60 mg QD (no added benefit >20 mg)
Generalized anxiety disorder (GAD)	Adults	20 mg QD	20 mg QD	50 mg QD (no added benefit >20 mg)
All indications	Elderly, severe renal or severe hepatic impairment	10 mg QD		40 mg QD

Titration Increase in 10 mg/day increments at intervals of at least 1 week

Renal Severe renal impairment: start 10 mg QD, max 40 mg/day.

Hepatic Severe hepatic impairment: start 10 mg QD, max 40 mg/day.

Instructions

Administer as a single daily dose in the morning, with or without food
When discontinuing, taper gradually (e.g., decrease by 10 mg/day at weekly intervals) rather than stopping abruptly
Allow at least 14 days between an MAOI and paroxetine in either direction

Available strengths

tab 10, 20, 30, 40 mg
cap 7.5 mg
ER tab 12.5, 25, 37.5 mg
susp 10 mg/5 mL

Contraindications

MAOIs (concurrently or within 14 days) due to risk of serotonin syndrome
Concomitant use of thioridazine — risk of QT prolongation
Concomitant use of pimozide — risk of QT prolongation

Cautions

Serotonin syndrome
Suicidal thoughts and behaviors (patients ≤24 yr)
Embryofetal toxicity (cardiovascular malformations with 1st-trimester exposure)
Increased bleeding risk (with NSAIDs, antiplatelets, anticoagulants)
Activation of mania/hypomania — screen for bipolar disorder
Discontinuation syndrome
Seizures
Angle-closure glaucoma
Hyponatremia/SIADH (especially elderly)
Reduced tamoxifen efficacy (CYP2D6 inhibition)
Bone fracture
Sexual dysfunction

Adverse reactions

Nausea, dry mouth, constipation, diarrhea, decreased appetite
Somnolence, insomnia, dizziness, tremor, asthenia
Sweating
Sexual dysfunction: abnormal ejaculation, impotence, decreased libido

Pregnancy <2-fold increase in cardiovascular malformations with 1st-trimester exposure; risks of PPHN, poor neonatal adaptation, and postpartum hemorrhage.

Lactation Present in human milk; monitor infant for agitation, irritability, poor feeding, and poor weight gain.

Cost

Paroxetine (PAXIL)

What pharmacies pay · NADAC 9/30/26

Strength		#/mo	generic $/mo	CostPlus
10 mg	tab	30 qd	$1.86	offered
20 mg	tab	30 qd	$1.83	offered
30 mg	tab	30 qd	$2.86	offered
40 mg	tab	30 qd	$2.90	offered

Other forms: Paroxetine CR (PAXIL CR)

Generic entry2017

Serotonin and MAOI

Provisional washout figures

SRI significance4 / 4

MAO-A inhibition0 / 4

Serotonin release0 / 4

Elevating mechanismSRI

Non-elevating actionNone recorded

Exposure dependenceTherapeutic exposure; severe toxicity requires meaningful MAO-A inhibition

Washout BEFORE an MAOI14 days

Evidence confidenceHigh

InterpretationPotent clinically significant SRI; severe serotonin toxicity is expected with meaningful MAO-A inhibition. A second SRI generally represents therapeutic duplication/additive adverse effects, not the classic life-threatening interaction.

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Memory aids: interaction avatars

CYP2D6 inhibitor (strong)

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Self-check

Paroxetine: Which activation-dependent cancer drug is compromised by its CYP2D6 inhibition?
Tamoxifen.
Paroxetine: Why is withdrawal prominent?
Short persistence.