Paroxetine

AEMPS

Selective serotonin reuptake inhibitor (SSRI)

ATC code: N06AB05

Brand names: Paxil, Seroxat, Motivan

Updated 21 Jul 2026 · Methodology

Indications

Generalized anxiety disorder

First line

First-line for generalized anxiety disorder. Effect at 4–6 weeks. Dose 20–50 mg daily.

Sources

AEMPS: Ficha técnica de Paroxetina (2024)
Am J Psychiatry: Paroxetine treatment of generalized anxiety disorder: a double-blind, placebo-controlled study. (2003)
BMC Psychiatry: Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. (2014)
The Lancet: Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis (2019)

ICD-10: F41.1 · ICD-11: 6B00

Major depressive disorder

Second line

Second-line for major depressive disorder per NG222 (2022) after sertraline and escitalopram. Dose 20–50 mg once daily in the morning. Worse tolerability than other SSRIs due to severe discontinuation syndrome, weight gain, and sexual dysfunction. Cipriani 2018 showed efficacy comparable to other SSRIs but worse tolerability.

Sources

ICD-10: F32.9 · ICD-11: 6A70.Z

Obsessive-compulsive disorder

First line

First-line for obsessive-compulsive disorder at high doses 40–60 mg once daily. Effect at 8–12 weeks.

Sources

ICD-10: F42 · ICD-11: 6B20

Panic disorder

First line

First-line for panic disorder. Dose 20–60 mg once daily. Low start dose (10 mg) with slow titration – anxiety worsening possible in first weeks.

Sources

ICD-10: F41.0 · ICD-11: 6B01

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

Stress and anxiety

Not recommended

Paroxetine is an SSRI antidepressant. It is prescribed for depression, generalized anxiety disorder, panic disorder, social anxiety, and post-traumatic stress disorder ( 2022 and NG222 guidelines). For emotional regulation or workplace stress, paroxetine does not work: no clinical studies of such use exist. Paroxetine has the most severe discontinuation syndrome among SSRIs: abrupt stopping causes dizziness, brain-zaps, nausea, and anxiety, sometimes lasting weeks. Other risks: sexual dysfunction, weight gain, teratogenicity ( category D, risk of fetal cardiac defects), and increased suicide risk in young adults (FDA boxed warning). If paroxetine was prescribed for emotional regulation, consider seeking a second opinion.

Sources

ICD-10: F41.9 · ICD-11: 6B0Z

How to read tiers A–F

AStrong evidence – first or second line in international guidelines
BRecommended in selected cases
CStudy data contradict each other
DBenefit not proven, no documented harm
FDocumented harm, or risk without benefit

Mechanism of action

The most serotonin-selective SSRI with mild additional anticholinergic action. Also a strong CYP2D6 inhibitor – significantly raises metoprolol, codeine (blocks morphine conversion), tramadol, tamoxifen levels (breast cancer recurrence risk). Short 21-hour half-life and active metabolite without accumulation – the worst discontinuation syndrome among SSRIs.

Safety

Boxed warning

FDA boxed warning: antidepressants increase suicidal ideation and behavior risk in children, adolescents, and young adults under 24 during the first weeks.

Contraindications

Paroxetine hypersensitivity
Concurrent MAO inhibitors or within 14 days of stopping
Concurrent thioridazine, pimozide (QT prolongation risk)
Concurrent tamoxifen (reduced breast cancer efficacy)
Pregnancy (category D)
Age under 18

Serious adverse effects

Severe discontinuation syndrome on abrupt stop
Serotonin syndrome with other serotonergic drugs
Hyponatremia (SIADH) in older adults
Bleeding with antiplatelets or anticoagulants
Suicidal thoughts (especially under 24)
Manic episode in bipolar patients

Common adverse effects

Nausea
Drowsiness
Dry mouth
Weight gain
Sexual dysfunction (more marked than other SSRIs)
Constipation
Sweating

Pregnancy: can you take Paroxetine?

AEMPS summary of product characteristics (section 4.6): several epidemiological studies suggest an increased risk of congenital malformations, particularly cardiovascular (ventricular and atrial septal defects), after paroxetine use in the first trimester; the mechanism is unknown. The risk of a cardiovascular malformation after maternal paroxetine exposure is under 2%, compared with about 1% expected in the general population. Paroxetine is used in pregnancy only when strictly indicated, alternative treatments are considered for women who are pregnant or wish to become pregnant, and abrupt discontinuation is avoided. After use late in pregnancy, especially in the third trimester, newborns are assessed carefully: serotonergic or withdrawal symptoms may occur, including respiratory distress, cyanosis, apnoea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycaemia, hypertonia or hypotonia, tremor, irritability and somnolence, in most cases immediately or within 24 hours of delivery. SSRI use in pregnancy, particularly late in pregnancy, may increase the risk of persistent pulmonary hypertension of the newborn (about 5 cases per 1,000 pregnancies versus 1–2 per 1,000 in the general population), and SSRI or SNRI exposure in the month before delivery raises the risk of postpartum haemorrhage (less than twofold).

Breastfeeding: can you take Paroxetine?

Low milk concentrations. Compatible with breastfeeding.

RID, infant dose via milk: 2%

Calculate RID Full profile on NIH LactMed ↗

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Practical notes

Common myths

Myth: «paroxetine can be stopped abruptly, no discontinuation syndrome.» Fact: paroxetine has the worst SSRI discontinuation syndrome – dizziness, paresthesia («brain zaps»), insomnia, anxiety, flu-like symptoms in 30–60% of patients on abrupt stop. Taper gradually: 10 mg every 1–2 weeks; with severe reaction, even slower; cross-taper to escitalopram or sertraline. Myth: «paroxetine is safe in pregnancy like all SSRIs.» Fact: T1 paroxetine is linked to a small rise in cardiac defect risk (CDC 2007, recategorized to D in 2005). Sertraline with more data and no described cardiac teratogenicity is preferred in pregnancy.

Drug–drug interactions

3 pairs found. Sorted from critical to minor.

CriticalPhenelzineAntidepressant, irreversible non-selective monoamine oxidase inhibitor (MAO-A and MAO-B)

Mechanism

Paroxetine is an SSRI with additional antimuscarinic activity. Combined with phenelzine causes serotonin syndrome plus additive sedation.

Symptoms

Hyperthermia, myoclonus, tachycardia, marked sedation.

Management

Combination contraindicated. 2-week washout.

Sources

Pair details →Phenelzine →

MajorRisperidoneAtypical antipsychotic – dopamine and serotonin receptor antagonist

Mechanism

Paroxetine is a strong CYP2D6 inhibitor. Risperidone rises 4-fold – enhanced hyperprolactinaemia and sedation.

Symptoms

Sedation, extrapyramidal symptoms, hyperprolactinaemia.

Management

Reduce risperidone by 50%. Alternative SSRI – sertraline or escitalopram (no CYP2D6 inhibition).

Sources

Pair details →Risperidone →

MajorTamoxifenSelective estrogen receptor modulator (SERM)

Mechanism

Tamoxifen is a prodrug: CYP2D6 converts it to endoxifen, one of its most active forms. Paroxetine is a strong CYP2D6 inhibitor. The data cited in the Spanish SmPCs of both drugs show a 65–75% fall in endoxifen levels with CYP2D6 inhibitors. In some studies tamoxifen efficacy dropped with paroxetine, up to higher breast cancer relapse and mortality; other studies found no such effect, as the label notes.

Symptoms

Tumour progression on imaging after 6–12 months.

Management

Avoid paroxetine during tamoxifen therapy where possible, as the Spanish SmPCs of both drugs require. The label advises an antidepressant with little or no CYP2D6 inhibition. The Spanish SmPC describes venlafaxine as a relatively weak CYP2D6 inhibitor. Sertraline also inhibits CYP2D6 (mild to moderate), and escitalopram doubled desipramine and metoprolol levels in studies. Fluoxetine and bupropion are strong CYP2D6 inhibitors, like paroxetine. If depression does not respond to the switch, oncology and psychiatry agree the regimen together.

Sources

Pair details →Tamoxifen →

Label mentions120 mentions

Verbatim lines from the interaction sections, in the language of the label

From this drug’s label

CriticalIMAOclass named in the label
«Está contraindicado el uso de paroxetina en combinación con inhibidores de la monoaminooxidasa (IMAOs). En circunstancias excepcionales, linezolid (un antibiótico que es un inhibidor reversible no…»
AEMPS, section 4.3 · Open on CIMA
CriticalLinezolid
«CONTRAINDICATIONS: Taking, or within 14 days of stopping, MAOIs (including the MAOIs linezolid and intravenous methylene blue) because of an increased risk of serotonin syndrome [see Warnings and…»
FDA, section 4 · Open on DailyMed
CriticalMAO inhibitorsclass named in the label
«CONTRAINDICATIONS: Taking, or within 14 days of stopping, MAOIs (including the MAOIs linezolid and intravenous methylene blue) because of an increased risk of serotonin syndrome [see Warnings and…»
FDA, section 4 · Open on DailyMed
CriticalMoclobemide
«al menos 24 horas después de la interrupción del tratamiento con un IMAO reversible (ej.: moclobemida, linezolid , cloruro de metiltionina (azul de metileno; agente de visualización preoperatoria el…»
AEMPS, section 4.3 · Open on CIMA
CriticalPimozide
«Paroxetina no se debe usar en combinación con pimozida (ver sección 4.5).»
AEMPS, section 4.3 · Open on CIMA
CriticalPimozide
«CONTRAINDICATIONS: Taking pimozide because of risk of QT prolongation [see Warnings and Precautions ( 5.3 ), Drug Interactions ( 7 )].»
FDA, section 4 · Open on DailyMed
Majorantidepresivos tricíclicosclass named in the label
«Inhibición del isoenzima CYP2D6: Como con otros antidepresivos, entre los que se encuentran otros inhibidores selectivos de la recaptación de serotonina (ISRS), paroxetina inhibe el isoenzima CYP2D6…»
AEMPS, section 4.5 · Open on CIMA
MajorAtomoxetine
«Inhibición del isoenzima CYP2D6: Como con otros antidepresivos, entre los que se encuentran otros inhibidores selectivos de la recaptación de serotonina (ISRS), paroxetina inhibe el isoenzima CYP2D6…»
AEMPS, section 4.5 · Open on CIMA
MajorFentanyl
«Fármacos serotoninérgicos: Se aconseja precaución y un estrecho control del paciente cuando se combinan fármacos con actividad serotoninérgica (incluyendo L-triptófano, triptanes, tramadol…»
AEMPS, section 4.5 · Open on CIMA
MajorFlecainide
«Inhibición del isoenzima CYP2D6: Como con otros antidepresivos, entre los que se encuentran otros inhibidores selectivos de la recaptación de serotonina (ISRS), paroxetina inhibe el isoenzima CYP2D6…»
AEMPS, section 4.5 · Open on CIMA
MajorL-tryptophan
«Fármacos serotoninérgicos: Se aconseja precaución y un estrecho control del paciente cuando se combinan fármacos con actividad serotoninérgica (incluyendo L-triptófano, triptanes, tramadol…»
AEMPS, section 4.5 · Open on CIMA
MajorLinezolid
«Está contraindicado el uso de paroxetina en combinación con inhibidores de la monoaminooxidasa (IMAOs). En circunstancias excepcionales, linezolid (un antibiótico que es un inhibidor reversible no…»
AEMPS, section 4.3 · Open on CIMA
MajorLithium
«Fármacos serotoninérgicos: Se aconseja precaución y un estrecho control del paciente cuando se combinan fármacos con actividad serotoninérgica (incluyendo L-triptófano, triptanes, tramadol…»
AEMPS, section 4.5 · Open on CIMA
MajorMeperidine
«Fármacos serotoninérgicos: Se aconseja precaución y un estrecho control del paciente cuando se combinan fármacos con actividad serotoninérgica (incluyendo L-triptófano, triptanes, tramadol…»
AEMPS, section 4.5 · Open on CIMA
MajorMetoprolol
«Inhibición del isoenzima CYP2D6: Como con otros antidepresivos, entre los que se encuentran otros inhibidores selectivos de la recaptación de serotonina (ISRS), paroxetina inhibe el isoenzima CYP2D6…»
AEMPS, section 4.5 · Open on CIMA
MajorPropafenone
«Inhibición del isoenzima CYP2D6: Como con otros antidepresivos, entre los que se encuentran otros inhibidores selectivos de la recaptación de serotonina (ISRS), paroxetina inhibe el isoenzima CYP2D6…»
AEMPS, section 4.5 · Open on CIMA
MajorRisperidone
«Inhibición del isoenzima CYP2D6: Como con otros antidepresivos, entre los que se encuentran otros inhibidores selectivos de la recaptación de serotonina (ISRS), paroxetina inhibe el isoenzima CYP2D6…»
AEMPS, section 4.5 · Open on CIMA
MajorTamoxifen
«Inhibición del isoenzima CYP2D6: En la literatura se ha notificado una interacción farmacocinética entre inhibidores de CYP2D6 y tamoxifeno que muestra una reducción del 65-75% en los niveles…»
AEMPS, section 4.5 · Open on CIMA
MajorTamoxifen
«DRUG INTERACTIONS: Concomitant use with tamoxifen: Consider use of an alternative antidepressant with little or no CYP2D6 inhibition. ( 5.11 , 7 )»
FDA, section 7 · Open on DailyMed
MajorTramadol
«Fármacos serotoninérgicos: Se aconseja precaución y un estrecho control del paciente cuando se combinan fármacos con actividad serotoninérgica (incluyendo L-triptófano, triptanes, tramadol…»
AEMPS, section 4.5 · Open on CIMA
Majortriptanesclass named in the label
«Fármacos serotoninérgicos: Se aconseja precaución y un estrecho control del paciente cuando se combinan fármacos con actividad serotoninérgica (incluyendo L-triptófano, triptanes, tramadol…»
AEMPS, section 4.5 · Open on CIMA
ModerateAcetylsalicylic acid
«AINES y ácido acetilsalicílico, y otros antiagregantes plaquetarios: Puede aparecer interacción farmacodinámica entre paroxetina y AINEs/ácido acetilsalicílico. El uso concomitante puede conducir a…»
AEMPS, section 4.5 · Open on CIMA
ModerateAINEclass named in the label
«AINES y ácido acetilsalicílico, y otros antiagregantes plaquetarios: Puede aparecer interacción farmacodinámica entre paroxetina y AINEs/ácido acetilsalicílico. El uso concomitante puede conducir a…»
AEMPS, section 4.5 · Open on CIMA
Moderateantiagregantesclass named in the label
«AINES y ácido acetilsalicílico, y otros antiagregantes plaquetarios: Puede aparecer interacción farmacodinámica entre paroxetina y AINEs/ácido acetilsalicílico. El uso concomitante puede conducir a…»
AEMPS, section 4.5 · Open on CIMA
Moderateantiarrítmicosclass named in the label
«Inhibición del isoenzima CYP2D6: Como con otros antidepresivos, entre los que se encuentran otros inhibidores selectivos de la recaptación de serotonina (ISRS), paroxetina inhibe el isoenzima CYP2D6…»
AEMPS, section 4.5 · Open on CIMA
Moderateanticoagulantesclass named in the label
«Anticoagulantes orales: Puede aparecer interacción farmacodinámica entre paroxetina y los anticoagulantes orales. El uso concomitante de paroxetina con anticoagulantes orales puede conducir a un…»
AEMPS, section 4.5 · Open on CIMA
Moderateanticoagulantsclass named in the label
«DRUG INTERACTIONS: Intervention Inform patients of the increased risk of bleeding associated with the concomitant use of paroxetine and antiplatelet agents and anticoagulants. For patients taking…»
FDA, section 7 · Open on DailyMed

From other drugs’ labels

CriticalPhenelzine
«CONTRAINDICATIONS: There have been reports of serious reactions (including hyperthermia, rigidity, myoclonic movements and death) when serotoninergic drugs (e.g., dexfenfluramine, fluoxetine…»
FDA, section 4 · Open on DailyMed
CriticalPimozide
«Está contraindicado el uso concomitante de Orap/Orap Fuerte con inhibidores de la recaptación de serotonina, tales como, sertralina, paroxetina, citalopram y escitalopram. (ver sección 4.5).»
AEMPS, section 4.3 · Open on CIMA
CriticalPimozide
«CONTRAINDICATIONS: Clinical drug interaction studies have demonstrated that pimozide is also metabolized by CYP 2D6. Concomitant use of pimozide with paroxetine and other strong CYP 2D6 inhibitors is…»
FDA, section 4 · Open on DailyMed
CriticalSelegiline
«CONTRAINDICATIONS: • EMSAM (selegiline transdermal system) is contraindicated with selective serotonin reuptake inhibitors (SSRIs, e.g., fluoxetine, sertraline, and paroxetine); serotonin and…»
FDA, section 4 · Open on DailyMed
CriticalTranylcypromine
«Síndrome serotoninérgico: Los casos sospechosos de interacciones de antidepresivos prescritos con frecuencia (por ejemplo, citalopram, paroxetina, venlafaxina, duloxetina, amitriptilina) con…»
AEMPS, section 4.4 · Open on CIMA
MajorAripiprazole
«Drugs Having Clinically Important Interactions with Aripiprazole: Strong CYP3A4 Inhibitors (e.g., itraconazole, clarithromycin) or strong CYP2D6 inhibitors (e.g., quinidine, fluoxetine, paroxetine)…»
FDA, section 7 · Open on DailyMed
MajorBupropion
«DRUG INTERACTIONS: • CYP2B6 inducers: Dose increase may be necessary if coadministered with CYP2B6 inducers (e.g., ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, and phenytoin) based…»
FDA, section 7 · Open on DailyMed
MajorDarunavir
«Established and Other Potentially Significant Drug Interactions: Antidepressants : Selective Serotonin Reuptake Inhibitors (SSRIs): paroxetine, sertraline Tricyclic Antidepressants (TCAs)…»
FDA, section 7 · Open on DailyMed
MajorDextromethorphan
«- Antidepresivos inhibidores de la monoaminoxidasa (IMAO) como moclobemida y tranilcipromina; antidepresivos inhibidores de la recaptación de la serotonina (ISRS) como fluoxetina y paroxetina…»
AEMPS, section 4.5 · Open on CIMA
MajorMetoprolol
«CYP2D6 Inhibitors: Drugs that are strong inhibitors of CYP2D6 such as quinidine, fluoxetine, paroxetine, and propafenone were shown to double metoprolol concentrations. While there is no information…»
FDA, section 7 · Open on DailyMed
MajorRisperidone
«Pharmacokinetic-related Interactions: The dose of risperidone should be adjusted when used in combination with CYP2D6 enzyme inhibitors (e.g., fluoxetine, and paroxetine) and enzyme inducers (e.g…»
FDA, section 7 · Open on DailyMed
MajorTamoxifen
«Inhibidores del CYP2D6: En publicaciones científicas se han descrito interacciones farmacocinéticas con inhibidores del CYP2D6, mostrando una reducción del 65-75% en los niveles plasmáticos de una de…»
AEMPS, section 4.5 · Open on CIMA
ModerateAmitriptyline
«Potencial de otros medicamentos para afectar a la amitriptilina: Inhibidores de CYP2D6 : Diversos fármacos como, p. ej., los neurolépticos, los inhibidores de la recaptación de serotonina, los…»
AEMPS, section 4.5 · Open on CIMA

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Frequently asked

What is Paroxetine used for?

Paroxetine is evaluated for the following indications with varying evidence strength: Generalized anxiety disorder (evidence tier A), Panic disorder (evidence tier A), Obsessive-compulsive disorder (evidence tier A). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Paroxetine?

Common side effects of Paroxetine (≥ 1 in 100): Nausea, Drowsiness, Dry mouth, Weight gain, Sexual dysfunction (more marked than other SSRIs), Constipation. See the Safety section for uncommon and serious reactions.

Is Paroxetine safe during pregnancy?

Is Paroxetine compatible with breastfeeding?

Low milk concentrations. Compatible with breastfeeding.

Who should not take Paroxetine?

Paroxetine is contraindicated in: Paroxetine hypersensitivity; Concurrent MAO inhibitors or within 14 days of stopping; Concurrent thioridazine, pimozide (QT prolongation risk); Concurrent tamoxifen (reduced breast cancer efficacy); Pregnancy (category D). Full list in the Safety section.

Does Paroxetine carry an FDA boxed warning?

FDA boxed warning: antidepressants increase suicidal ideation and behavior risk in children, adolescents, and young adults under 24 during the first weeks.

Official sources

Direct links to regulator labels. Open in a new tab.

AEMPS / CIMA
FDA / DailyMedLabel dated 08/11/2026

Other drugs in this group

Phenelzine, Phenylpiracetam (fonturacetam), Phosphatidylserine, Picamilon (nicotinoyl-GABA), Saffron (Crocus sativus stigma extract), Agomelatine, Cortexin (bovine brain cortex polypeptides), Hopantenic acid (calcium hopantenate)