Paroxetine
Paroxetine is one of the older SSRI antidepressants, marketed as Paxil and Seroxat. It has a stronger anticholinergic profile and shorter half-life than other SSRIs, which makes its discontinuation syndrome notably more pronounced and warrants careful tapering.
- Chemical formula
- C19H20FNO3
- CAS number
- 61869-08-7
- ATC code
- N06AB05
- Molecular weight
- 329.37 g/mol
- Drug class
- Selective serotonin reuptake inhibitor (SSRI)
- Also known as
- Paxil, Seroxat, Aropax
What is it?
Paroxetine is an SSRI approved by the FDA in 1992, marketed as Paxil by SmithKline Beecham (now GlaxoSmithKline) and as Seroxat in many other markets. It was once one of the most prescribed antidepressants worldwide, but use has declined relative to escitalopram and sertraline because of paroxetine's notable discontinuation syndrome and weight-gain profile. Authorised generic paroxetine is widely available.
Mechanism of action
Paroxetine selectively inhibits the serotonin reuptake transporter, increasing serotonin availability at the synapse. It is the most potent SSRI for SERT inhibition and has additional weak anticholinergic activity, which contributes both to therapeutic effect (sleep, anxiety) and side effects (dry mouth, constipation). The therapeutic effect builds over 4–6 weeks, similar to other SSRIs.
Pharmacokinetics
Paroxetine is well absorbed after oral administration with bioavailability of approximately 50%. Peak plasma concentrations occur 5 hours post-dose. The terminal half-life is approximately 21 hours, supporting once-daily dosing. Hepatic metabolism is via CYP2D6 — paroxetine is both a substrate and a strong inhibitor of CYP2D6, which causes meaningful interactions with other CYP2D6-metabolised medications.
Indications
Paroxetine is approved for major depressive disorder, generalised anxiety disorder, social anxiety disorder, panic disorder, obsessive-compulsive disorder and post-traumatic stress disorder, with regional variation. It is also approved for menopausal vasomotor symptoms (hot flashes) at lower doses (Brisdelle 7.5mg). Use during pregnancy is generally avoided due to evidence of fetal cardiovascular malformations.
Safety profile
Common adverse effects include nausea, sexual dysfunction (more pronounced than with most SSRIs), weight gain, sleep disturbance, fatigue and anticholinergic symptoms. The most clinically important issue is the discontinuation syndrome — paroxetine produces a particularly intense withdrawal syndrome (dizziness, sensory disturbances, flu-like symptoms) on abrupt cessation, even after short-term use, requiring slow tapering.
Products containing this ingredient
Frequently asked questions
Why does paroxetine have a difficult discontinuation? ▾
Paroxetine's relatively short half-life and CYP2D6 metabolism produce rapid plasma drops on cessation, triggering a classic SSRI discontinuation syndrome — dizziness, sensory disturbances ('brain zaps'), flu-like symptoms — that is notably more pronounced than with longer-half-life SSRIs like fluoxetine. According to the prescribing information, paroxetine should be tapered slowly, typically over weeks to months.
Is paroxetine still a good first-line antidepressant? ▾
Paroxetine is effective but is now generally considered a later-line option compared with escitalopram or sertraline because of its discontinuation profile, weight gain and CYP2D6 interactions. According to current guidelines, escitalopram and sertraline are usually preferred as first-line SSRIs in adults without prior antidepressant history.
Can paroxetine be used in pregnancy? ▾
Paroxetine is generally avoided in pregnancy, particularly in the first trimester, because of evidence linking it to fetal cardiovascular malformations. According to current guidelines, women of reproductive age starting an SSRI should usually be offered an alternative if pregnancy is planned or possible.
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