Paroxetine
PAXIL
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.
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
FDA label
Read the full label on DailyMed ↗
| 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
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.
⚠ BOXED WARNING
- Suicidal thoughts and behaviors in patients under 25
Cost, est. cash$10–$300/month
Generic entry2017
Classes and tags
Clinical profile
Legacy pregnancy categoryD
Defining liabilityAnticholinergic burden, sexual dysfunction, withdrawal and strong CYP2D6 inhibition.
Mechanism of action: Paroxetine ballicule
Open Paroxetine in the interactive console ↗
Memory aids: mascots and interaction avatars
Crimson roses → antimuscarinic effects
