Paroxetine (Paxil)

Pharmacokinetics of Paroxetine

Paroxetine: Cytochrome P450 Metabolism

Substrate of (Metabolized by)
Inhibits 1A2, 2D6 (potent!)
  • Paroxetine is a very “sloppy” SSRI, meaning it targets other receptors like histamine (sedation and weight gain) and muscarinic receptors (which makes it highly anticholinergic)
    • When it is discontinued, there can be high cholinergic rebound when you stop paroxetine
    • When H1 is suddenly unblocked, people get jittery and insomnia
  • Paroxetine also has adrenergic effects, it could almost be considered like a serotonin norepinephrine reuptake inhibitor.

Dosing for Paroxetine

Starting 20 mg PO daily
Maximum 60 mg PO daily
  • Paroxetine comes in oral formulation.
  • Paroxetine is a very potent serotonergic agent, hence why the discontinuation and withdrawal symptoms can be so bad!
    • This is one reason to avoid using paroxetine as the first medication of choice, even though there are many studies on it.
  • The half-life also varies significantly, complicating withdrawal symptoms.
  • If a patient has difficulty tapering off paroxetine due to discontinuation symptoms, fluoxetine can be added as a 2 week course of therapy to help with taper (e.g. 10 mg fluoxetine)
  • Tamoxifen - paroxetine inhibits CYP 2D6 which inhibits the conversion of tamoxifen to its active metabolite. Do not use paroxetine in women with breast cancer on tamoxifen!
  • Anticholinergic activity can cause more sedation compared to other SSRIs
  • Nitric oxide synthetase inhibition may also increase sexual dysfunction
  • Paroxetine is associated with increased risk for cardiac defects in the fetus, and should not be used in pregnant women.[1]