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Paroxetine (Paxil, Paxil CR)

SSRI • Last reviewed 2025-09-26

General information

Paroxetine is an SSRI with broad FDA indications including major depressive disorder, OCD, panic disorder, social anxiety disorder, generalized anxiety disorder, PTSD, and PMDD.

Immediate-release tablets/capsules (10–40 mg) and controlled-release tablets (12.5–37.5 mg) support once-daily dosing. Evening dosing may mitigate daytime sedation.

Paroxetine frequently causes weight gain, anticholinergic effects, and discontinuation syndrome due to a short half-life. It is a potent CYP2D6 inhibitor, complicating polypharmacy.

Contraindicated in pregnancy (Category D) due to increased risk of fetal cardiac malformations; alternative SSRIs preferred for women planning conception.

Dosing & administration

MDD/Panic/OCD: start 20 mg once daily; increase by 10 mg at ≥1-week intervals up to 50 mg/day (IR) or 62.5 mg/day (CR).

GAD/PTSD/SAD: start 20 mg/day; typical range 20–50 mg/day.

PMDD: 12.5 mg (CR) daily continuously or luteal-phase dosing.

Mechanism of action

Potent inhibitor of the serotonin transporter with minimal effect on norepinephrine or dopamine transporters.

Metabolism & pharmacokinetics

Nonlinear pharmacokinetics due to CYP2D6 saturation. Peak concentrations reached ~6 hours post-dose (IR) or ~10 hours (CR). Extensive hepatic metabolism; half-life ~21–24 hours but prolonged with chronic dosing.

Drug interactions

Avoid MAOIs, linezolid, methylene blue (serotonin syndrome).

Strong CYP2D6 inhibition increases levels of TCAs, antipsychotics, tamoxifen (reducing efficacy).

Use caution with other serotonergic agents or CNS depressants.

Monitoring & safety checks

Discontinuation guidance

Taper slowly (over ≥4 weeks) due to high risk of discontinuation syndrome; consider switching to a longer half-life SSRI for cross-taper if symptoms emerge.

References

  1. Paroxetine Prescribing Information — DailyMed
  2. Paroxetine safety and tolerability review — CNS Drugs (2022)
  3. CANMAT 2024 Depression Guidelines (2024)

Educational use only — verify details in current prescribing information and authoritative clinical guidelines before making prescribing decisions.