Paxil
paroxetine
Boxed Warning
Suicidality risk in children, adolescents, and young adults under 25 during initial treatment.
Overview
Paroxetine is an SSRI with notable anticholinergic activity, approved for major depressive disorder, OCD, panic disorder, social anxiety disorder, GAD, and PTSD. It is widely recognized as one of the more difficult SSRIs to discontinue.
10mg, 20mg, 30mg, 40mg
Tablets: 10mg, 20mg, 30mg, 40mg; Oral suspension: 10mg/5mL; Controlled-release (CR) tablets: 12.5mg, 25mg, 37.5mg
Category D (positive evidence of risk — cardiac malformations)
Mechanism of Action
Potent and selective inhibitor of serotonin reuptake (SERT). Also has significant anticholinergic (muscarinic) activity and weak norepinephrine reuptake inhibition, which contribute to its withdrawal profile.
Taper Notes
Short half-life for an SSRI. Liquid formulation available. Often considered one of the harder SSRIs to taper.
Maudsley Deprescribing Guidance
Particularly difficult to stop due to short half-life and anticholinergic withdrawal. Very slow final taper essential.
Common Withdrawal Symptoms
Interactions & Safety
Drug Interactions
- MAOIs — contraindicated (serotonin syndrome risk)
- Thioridazine — contraindicated (QT prolongation via CYP2D6 inhibition)
- Pimozide — contraindicated
Food Interactions
- No significant food effect on absorption
- Avoid alcohol during treatment
Contraindications
- MAOIs within 14 days
- Thioridazine
- Pimozide
Toxicity
Serotonin syndrome risk. Anticholinergic toxicity at high doses. Associated with higher rates of discontinuation syndrome than other SSRIs.
Pharmacokinetics
ADME Profile
Completely absorbed after oral dosing but extensive first-pass metabolism reduces bioavailability to ~50%. Tmax ~5 hours. Food does not significantly affect absorption.
~8.7 L/kg
Extensively metabolized hepatically via CYP2D6 (primary) with CYP3A4 contribution. Paroxetine inhibits its own metabolism (CYP2D6 saturation), leading to non-linear pharmacokinetics.
Renal (~64% as metabolites, ~2% unchanged) and fecal (~36%).
~93–95%
Non-linear; clearance decreases at higher doses due to CYP2D6 saturation.
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