Paroxetine
PAXIL
Pronunciation: pa-ROX-e-teen (PAX-il)
“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.
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
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
| 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
⚠ BOXED WARNING
- Suicidal thoughts and behaviors in patients under 25
Classes and tags
Clinical profile
Legacy pregnancy categoryD
Defining liabilityAnticholinergic burden, sexual dysfunction, withdrawal and strong CYP2D6 inhibition.
Serotonin and MAOI
Provisional washout figures
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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