Paroxetine
Paxil · Brisdelle
Selective Serotonin Reuptake InhibitorGeneric availableTDM data
The mechanism of action of paroxetine in the treatment of MDD, SAD, OCD\, PD, GAD, and PTSD is unknown, but is presumed to be linked to potentiation of serotonergic activity in the central nervous system resulting from inhibition of neuronal reuptake of serotonin (5-hydroxy-tryptamine, 5-HT).
Compare Paroxetine →FDA-Approved Indications
- Major depressive disorder (adults)
- Obsessive-compulsive disorder (adults)
- Panic disorder, with or without agoraphobia (adults)
- Social anxiety disorder (adults)
- Generalized anxiety disorder (adults)
- Posttraumatic stress disorder (adults)
Common Off-Label Uses
- Generalized anxiety disorder
- Premature ejaculation
- Vasomotor symptoms (menopause)
- Body dysmorphic disorder
What Sets This Drug Apart
- FDA-approved for 6 indications (MDD, OCD, PD, SAD, GAD, PTSD) — tied with sertraline for broadest SSRI indication set, but includes GAD (not PMDD)
- Nonlinear, saturable CYP2D6-mediated metabolism: steady-state exposure ~8x greater than predicted from single-dose data
- Strong CYP2D6 inhibitor with explicit tamoxifen interaction warning — label recommends alternative antidepressant
- Highest sexual dysfunction rates among SSRIs: ejaculation disorder 27%, sexual dysfunction 15%, libido decreased 13%
- Notable sedation: somnolence 23% — highest among labeled SSRI rates
- Increased risk of cardiovascular malformations in first-trimester exposure (OR 1.8, 95% CI 1.1–2.8); historical Category D
- Anticholinergic-like side effect profile: dry mouth 20.6%, constipation 13%, blurred vision
- Cipriani 2018 MDD response OR 1.75 (95% CrI 1.61–1.90) — highest among SSRIs, in the 'more effective' group
- Henssler 2024 severe-symptom discontinuation rate 0.053 (95% CI 0.025–0.107, k=4) — ~2x pooled AD average
- Weight gain ≥7% in extended treatment; most weight-gaining SSRI per labeled rates
Boxed Warning
SUICIDAL THOUGHTS AND BEHAVIORS