Paroxetine

ATC code

N06AB05

Therapeutic class

Antidepressant (Selective Serotonin Reuptake Inhibitor) · Selective Serotonin Reuptake Inhibitor

Forms

film-coated tablet

Brand names

Frosinor (ES) · Paxil (US) · Seroxat (EU) · Deroxat (FR)

Overall confidence

medium

Regulatory sources consulted

AEMPS CIMA FT 59466: https://cima.aemps.es/cima/dochtml/ft/59466/FT_59466.html
Flockhart Table (CYP450)
CredibleMeds.org
PMID:19726629
AEMPS CIMA · nº registro 59466 ↗
RxNorm rxcui 32937 ↗

Approved indications

Major depressive episode
Obsessive compulsive disorder (OCD)
Panic disorder with or without agoraphobia
Social anxiety disorder / social phobia
Generalized anxiety disorder
Post-traumatic stress disorder (PTSD)

Contraindications

Absolute

Hypersensitivity to the active substance or to any of the excipients.
Concomitant use with monoamine oxidase inhibitors (MAOIs). At least 14 days should elapse after discontinuing an irreversible MAOI.
Concomitant use with thioridazine or pimozide.

Clinical warnings

Boxed warning · Increased risk of suicidal thinking and behavior in children, adolescents, and young adults (under 25 years old). — FDA
Major warning · Serotonin syndrome: increased risk with concomitant use of other serotonergic agents. Monitoring is required. — EMA SPC
Withdrawal symptoms upon treatment discontinuation: discontinuation should be gradual to avoid dizziness, sensory disturbances, anxiety, and nausea. — EMA SPC

Drug interactions

HighMAO Inhibitors (e.g., Phenelzine, Selegiline)N06AF
Mechanism: Excessive increase in serotonin levels, risk of life-threatening serotonin syndrome.
Recommendation: Contraindicated. Allow a washout period of at least 14 days between stopping one and starting the other.
EMA SPC
HighTamoxifenL02BA01
Mechanism: Paroxetine is a potent CYP2D6 inhibitor, the enzyme required to convert tamoxifen to its active metabolite, endoxifen. This may reduce tamoxifen's efficacy.
Recommendation: Avoid the combination. Consider an antidepressant with weak or no CYP2D6 inhibition (e.g., citalopram, escitalopram, venlafaxine).
PMID:19726629DOI:10.1200/JCO.2009.23.2801
HighThioridazineN05AC02
Mechanism: Paroxetine inhibits the metabolism of thioridazine (via CYP2D6), increasing its plasma levels and the risk of QTc interval prolongation and serious ventricular arrhythmias.
Recommendation: Contraindicated.
EMA SPC

Adverse events

Common (≥1%)

nausea · sexual dysfunction · somnolence · insomnia · dizziness · headache · decreased appetite · sweating

Rare but serious

serotonin syndrome · hyponatremia · acute angle-closure glaucoma · gastrointestinal bleeding · seizures · severe cutaneous adverse reactions (SCARs)

Pregnancy and lactation

FDA category: D

Epidemiological studies suggest an increased risk of congenital malformations, particularly cardiovascular (ventricular and atrial septal defects), with first-trimester use of paroxetine. Use in the third trimester may be associated with persistent pulmonary hypertension of the newborn (PPHN). Use during pregnancy is not recommended unless strictly necessary.