Paroxetine
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: Paroxetine acts by selectively blocking the **serotonin transporter (SERT)** on the presynaptic neuronal membrane in the central nervous system. * Inhibition of **SERT** โ Decreased reuptake of **serotonin (5-HT)** from the synaptic cleft โ 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.
Dosing by species
- SSRI responsive behavior problems ยท 0.5-1 mg/kg q24h (2.5-5 mg per cat q24h) ยท PO ยท q24h
- Compulsive disorders ยท 0.5-1 mg/kg PO once daily (q24h) ยท PO ยท q24h
- Generalized anxiety disorder ยท 0.5-1.5 mg/kg q24h ยท PO ยท q24h
- Marking ยท 0.5-1 mg/kg PO once daily ยท PO ยท q24h
- Intercat aggression ยท 0.5-1 mg/kg PO once daily ยท PO ยท q24h
- SSRI responsive behavior problems ยท 0.5-1.5 mg/kg PO q24-48h ยท PO ยท q24-48h
- Urine marking (especially with overt aggression) ยท 0.5-1 mg/kg ยท PO ยท q24h ยท Long-term as needed ยท Can be increased to 2 mg/kg PO q24h but close monitoring is required. Monitor urination frequency.
- Compulsive disorders ยท 1 mg/kg (up to 3 mg/kg) PO once daily (q24h) ยท PO ยท q24h
- Generalized anxiety disorder ยท 1-1.5 mg/kg q24h ยท PO ยท q24h
- Adjunctive treatment of phobias, fears, and anxieties ยท 0.5-1 mg/kg PO once daily ยท PO ยท q24h
- Generalized anxiety and impulsivity ยท 1-2 mg/kg ยท PO ยท q24h ยท Long-term as needed ยท Fluoxetine or clomipramine may be preferable due to authorized veterinary status.
Routes of administration
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
- Anxiety
- 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
Drug interactions
- Buspirone ยท Increased risk for serotonin syndrome
- Cimetidine ยท May increase paroxetine levels
- Cyproheptadine ยท May decrease or reverse the effects of SSRIs
- Digoxin ยท Paroxetine (in humans) can decrease digoxin AUC by 15%
- Insulin ยท May alter insulin requirements
- Isoniazid ยท Increased risk for serotonin syndrome
- MAO Inhibitors (including amitraz and selegiline) ยท 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.
- Pentazocine ยท Serotonin syndrome-like adverse effects possible
- Phenobarbital ยท May decrease paroxetine levels
- Phenytoin ยท Increased plasma levels of phenytoin possible; may decrease paroxetine levels
- Propranolol, Metoprolol ยท Paroxetine may increase these beta-blockers' plasma levels and cause hypotension; atenolol may be safer
- Tramadol ยท SSRIs can inhibit the metabolism of tramadol to active metabolites, decreasing efficacy and increasing toxicity risk (serotonin syndrome, seizures)
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)
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.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturerโs current label.