Paroxetine
Paroxetine HCl
Also known as: Paxil CR · Pexeva · Seroxat · BRL-29060 · FG-7051 · Paroxetine hydrochloride · Paroxetina · Paroxetinum
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Dosing by species
🌎 NA — North America🌍 EU — Europe
Dogs
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Compulsive disorders | 1 mg/kg (up to 3 mg/kg) PO once daily (q24h) | PO | q24h | — | 🌎 NA |
| Generalized anxiety disorder | 1-1.5 mg/kg q24h | PO | q24h | — | 🌎 NA |
| Adjunctive treatment of phobias, fears, and anxieties | 0.5-1 mg/kg PO once daily | PO | q24h | — | 🌎 NA |
| Generalized anxiety and impulsivity | 1-2 mg/kg | PO | q24h | Long-term as needed | 🌍 EU |
- Generalized anxiety and impulsivity: Fluoxetine or clomipramine may be preferable due to authorized veterinary status.
Cats
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| SSRI responsive behavior problems | 0.5-1 mg/kg q24h (2.5-5 mg per cat q24h) | PO | q24h | — | 🌎 NA |
| Compulsive disorders | 0.5-1 mg/kg PO once daily (q24h) | PO | q24h | — | 🌎 NA |
| Generalized anxiety disorder | 0.5-1.5 mg/kg q24h | PO | q24h | — | 🌎 NA |
| Marking | 0.5-1 mg/kg PO once daily | PO | q24h | — | 🌎 NA |
| Intercat aggression | 0.5-1 mg/kg PO once daily | PO | q24h | — | 🌎 NA |
| SSRI responsive behavior problems | 0.5-1.5 mg/kg PO q24-48h | PO | q24-48h | — | 🌎 NA |
| Urine marking (especially with overt aggression) | 0.5-1 mg/kg | PO | q24h | Long-term as needed | 🌍 EU |
- Urine marking (especially with overt aggression): Can be increased to 2 mg/kg PO q24h but close monitoring is required. Monitor urination frequency.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Paroxetine is a potent Selective Serotonin Reuptake Inhibitor (SSRI) used off-label in veterinary medicine primarily for behavioral modification. It is structurally related to fluoxetine but possesses distinct pharmacokinetic and pharmacodynamic properties.
- Dogs: Used to treat aggression, stereotypic behaviors, obsessive-compulsive disorders (OCD), and generalized anxiety.
- Cats: Beneficial for managing urine marking, intercat aggression, and anxiety-related sleep disturbances.
Clinical Pearl: Compared to fluoxetine, paroxetine has a shorter half-life and no active metabolites, which may allow for a faster washout period if adverse effects occur. However, it also possesses mild anticholinergic properties, making constipation a more common side effect, particularly in felines.
Mechanism of action
Paroxetine acts by selectively blocking the serotonin transporter (SERT) on the presynaptic neuronal membrane in the central nervous system.
- Inhibition of SERT → Decreased reuptake of serotonin (5-HT) from the synaptic cleft → Increased concentration and prolonged activity of 5-HT at postsynaptic 5-HT receptors.
- This potentiation of serotonergic neurotransmission helps regulate mood, anxiety, and compulsive behaviors.
- Paroxetine has minimal affinity for dopamine or norepinephrine receptors, but does exhibit mild affinity for muscarinic acetylcholine receptors, contributing to its anticholinergic side effect profile.
Safety & warnings
Contraindications
- Patients with known hypersensitivity to paroxetine
- Patients receiving monoamine oxidase inhibitors (MAOIs)
- Known hypersensitivity to paroxetine or other SSRIs
- History of seizures or epilepsy
- Concurrent use of Monoamine Oxidase Inhibitors (MAOIs)
- Concurrent use of other serotonergic agents (due to serotonin syndrome risk)
Adverse effects
- Anorexia (common, usually transient)
- Lethargy
- GI effects
- Irritability
- Insomnia/hyperactivity
- Panting
- Aggressive behavior in previously unaggressive dogs
- Constipation (especially in cats)
- Changes in elimination patterns
- Changes in blood glucose levels
- Reduced seizure threshold
- Decreased appetite
- Vomiting
- Trembling
- Restlessness
- Gastrointestinal disturbance
- Paradoxical increase in anxiety
- Potential increase in aggression
- Changes in urination frequency (cats)
Precautions
Use with caution in patients with seizure disorders, or severe cardiac, hepatic, or renal disease. Dosages may need to be reduced in patients with severe hepatic or renal impairment.
If paroxetine is rapidly discontinued, withdrawal reactions can occur. If the patient has been receiving the drug for an extended period, a gradual withdrawal is recommended. Safety during pregnancy has not been established (FDA Category C in humans); use caution in nursing patients as the drug is excreted into milk at low levels.
Drug interactions
Increased risk for serotonin syndrome
May increase paroxetine levels
May decrease or reverse the effects of SSRIs
Paroxetine (in humans) can decrease digoxin AUC by 15%
May alter insulin requirements
Increased risk for serotonin syndrome
High risk for serotonin syndrome; use contraindicated. A 5-week washout period is required after discontinuing paroxetine, and a 2-week washout if discontinuing the MAOI first.
Serotonin syndrome-like adverse effects possible
May decrease paroxetine levels
Increased plasma levels of phenytoin possible; may decrease paroxetine levels
Paroxetine may increase these beta-blockers' plasma levels and cause hypotension; atenolol may be safer
SSRIs can inhibit the metabolism of tramadol to active metabolites, decreasing efficacy and increasing toxicity risk (serotonin syndrome, seizures)
Paroxetine may increase TCA blood levels and may increase the risk for serotonin syndrome
Increased plasma levels of theophylline possible
Paroxetine may increase the risk for bleeding
High risk of fatal serotonin syndrome. Do not use paroxetine within 2 weeks of an MAOI, and do not use an MAOI within 6 weeks of stopping paroxetine.
Paroxetine antagonizes the effects of anticonvulsants and lowers the seizure threshold.
May lower seizure threshold and increase risk of adverse neurological events.
Increased risk of bleeding in the case of tissue trauma.
Increased risk of bleeding.
Increased risk of serotonin syndrome. Use only in exceptional cases with careful monitoring.
Monitoring
- Efficacy of behavioral modification
- Adverse effects (including appetite and weight changes)
- Behavioral changes (efficacy, paradoxical anxiety, or increased aggression)
- Frequency of urination (especially in cats)
- Signs of serotonin syndrome (tremors, agitation, hyperthermia)
- Gastrointestinal tolerance (appetite, vomiting)
Pharmacokinetics
Half-life
Absorption
No veterinary data located. In humans, slowly but nearly completely absorbed from the GI tract. High first-pass effect means relatively small amounts reach systemic circulation unchanged. Food does not impair absorption.
Distribution
About 95% bound to plasma proteins.
Metabolism
Extensively metabolized, probably in the liver.
Elimination
Excreted primarily in urine as metabolites, with some fecal excretion.
Overdose
Experience with overdoses in humans yields a mixed picture; while not as toxic as tricyclic antidepressants, fatalities and significant morbidity have occurred.
- Clinical Signs: ASPCA APCC data (2008-2009) reported common findings in dogs including hyperactivity, lethargy, mydriasis, and trembling. In cats, mydriasis was commonly noted.
- Treatment: In small animal overdoses, err on the safe side. Employ gut evacuation (if not contraindicated) followed by supportive care. Activated charcoal is very effective in binding paroxetine.
- Serotonin Syndrome: If serotonin syndrome develops, phenothiazines and cyproheptadine can be effective for control. Contact an animal poison control center for additional guidance.
Available products
Formulations
- Controlled-release oral tablets
- Oral suspension
- 20 mg oral tablet
- 30 mg oral tablet
- 2 mg/ml oral liquid suspension
Human-labeled
- Paroxetine Oral Tablets: 10 mg, 20 mg, 30 mg & 40 mg; Paxil® (GlaxoSmithKline); Pexeva® (Synthon); generic; (Rx)
- Paroxetine Oral Tablets Controlled-release: 12.5 mg, 25 mg & 37.5 mg; Paxil® CR (GlaxoSmithKline); generic; (Rx)
- Paroxetine Oral Suspension: 2 mg/mL in 250 mL; Paxil® (GlaxoSmithKline); generic; (Rx)
- Paxil 20 mg, 30 mg tablets
- Seroxat 20 mg, 30 mg tablets
- Seroxat 2 mg/ml oral suspension
Regulatory status
POM (Prescription Only Medicine). Used under the prescribing cascade.
POM (Prescription Only Medicine). Used under the prescribing cascade.
No regulatory data for: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Paroxetine oral tablets should be stored at 15-30°C. The oral suspension should be stored below 25°C.
Client information
- Patience is Key: Behavioral medications like paroxetine can take several weeks (often 4-8 weeks) to show full effects. Do not stop the medication abruptly unless directed by your veterinarian.
- Administration: Can be given with or without food. If your pet experiences stomach upset, giving it with a small treat or meal may help.
- Side Effects: Watch for changes in appetite (eating less is common initially), lethargy, or gastrointestinal upset. In cats, monitor closely for constipation or changes in litter box habits.
- Safety: Keep medication strictly out of reach of children and other pets. Never give your pet human medications without veterinary approval, as dosages differ significantly.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.