Paroxetine (Paxil)

Primer

Paroxetine (Trade name: Paxil) is an antidepressant in the selective seronin reuptake inhibitor (SSRI) class used in the treatment various psychiatric disorders including: major depressive disorder, generalized anxiety disorder, posttraumatic stress disorder, social anxiety disorder, and obsessive compulsive disorder.

Pharmacokinetics

Pharmacokinetics of Paroxetine

Absorption
Distribution
Metabolism
Elimination
Half-life

Paroxetine: Cytochrome P450 Metabolism

Substrate of (Metabolized by)
Induces
Inhibits 1A2, 2D6 (potent!)

Pharmacodynamics

Mechanism of Action

  • 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.

Toxicity

Indications

Dosing

Dosing for Paroxetine

Starting 20 mg PO daily
Titration
Maximum 60 mg PO daily
Taper

Formulations

  • Paroxetine comes in oral formulation.

Monitoring

Withdrawal

  • 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)

Contraindications

Absolute

Relative

Drug-Drug Interactions

  • 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!

Side Effects

Adverse Events

Clinical Pearls

  • Anticholinergic activity can cause more sedation compared to other SSRIs
  • Nitric oxide synthetase inhibition may also increase sexual dysfunction

Special Populations

Geriatric

Pediatric

Obstetric and Fetal

  • Paroxetine is associated with increased risk for cardiac defects in the fetus, and should not be used in pregnant women.[1]

Medically Ill

Resources

References

1) Katzman, M. A., Bleau, P., Blier, P., Chokka, P., Kjernisted, K., & Van Ameringen, M. (2014). Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC psychiatry, 14(1), 1-83.