BLACK BOX WARNING
- suicidality in children, adolescents, and young adults
paroxetine
Brand: Paxil, Paxil CR, Pexeva
⚠ BBW Beers Criteria Prototype: fluoxetine
Drug Class: SSRI
Drug Family: antidepressant
Subclass: selective serotonin reuptake inhibitor
Organ Systems: cns
Mechanism of Action
Selectively inhibits the serotonin transporter (SERT), blocking presynaptic reuptake of serotonin and increasing its availability in the synapse. Paroxetine also has notable anticholinergic and noradrenergic reuptake inhibition activity compared to other SSRIs.
SERT (serotonin transporter)
Indications
- major depressive disorder
- generalized anxiety disorder
- panic disorder
- social anxiety disorder
- PTSD
- OCD
- premenstrual dysphoric disorder
Contraindications
- concurrent MAOI use
- concurrent thioridazine use
- concurrent pimozide use
Adverse Effects
Common
- nausea
- somnolence
- dry mouth
- constipation
- sexual dysfunction
- weight gain
- sweating
Serious
- serotonin syndrome
- suicidal ideation (pediatric/young adults)
- withdrawal syndrome on abrupt discontinuation
- hyponatremia (SIADH)
- QT prolongation
Pharmacokinetics (ADME)
| Absorption | well absorbed orally; bioavailability ~50% due to first-pass metabolism; food does not significantly affect absorption |
| Distribution | highly protein bound (~95%); Vd ~8-28 L/kg; distributes widely into tissues |
| Metabolism | extensively metabolized by CYP2D6 (major); potent inhibitor of CYP2D6; subject to saturable first-pass metabolism |
| Excretion | renal (~64%) and fecal (~36%); dose reduction in severe renal/hepatic impairment |
| Half-life | 21 hours (range 3-65 hours) |
| Onset | 1-4 weeks for antidepressant effect |
| Peak | 5.2 hours |
| Duration | 24 hours |
| Protein Binding | 95% |
| Vd | 8-28 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| MAOIs | serotonin syndrome risk | contraindicated |
| warfarin | increased bleeding risk via platelet serotonin depletion | moderate |
| tramadol | serotonin syndrome and CYP2D6 inhibition reduces tramadol activation | major |
| tamoxifen | CYP2D6 inhibition reduces conversion to active endoxifen, reducing efficacy | major |
| tricyclic antidepressants | CYP2D6 inhibition raises TCA levels | major |
Nursing Considerations
- Assess for suicidal ideation at each visit during first 4 weeks; paroxetine carries the highest discontinuation syndrome risk of all SSRIs due to short half-life and anticholinergic activity — never abrupt-stop.
- Monitor for weight gain and metabolic changes; paroxetine is associated with more weight gain than other SSRIs.
- Caution in elderly patients due to anticholinergic effects (urinary retention, constipation, confusion) and risk of falls.
- Educate patient that gradual taper is required on discontinuation; abrupt stopping causes dizziness, paresthesias, electric shock sensations ('brain zaps'), irritability, and flu-like symptoms.
Clinical Pearls
- Paroxetine is the only SSRI FDA-approved for all five anxiety disorders (GAD, panic, social anxiety, PTSD, OCD), making it useful in comorbid anxiety-depression.
- Paroxetine is a potent CYP2D6 inhibitor — avoid co-prescribing with tamoxifen (reduces anti-cancer efficacy) and increases levels of many drugs metabolized by 2D6.
Safety Profile
Pregnancy avoid
Lactation use-with-caution
Renal Adjustment Required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.