Fluoxetine
**Fluoxetine** is a widely used Selective Serotonin-Reuptake Inhibitor (SSRI) antidepressant utilized in veterinary medicine to manage a variety of behavioral disorders in dogs and cats. In dogs, it is FDA-approved (as Reconcileยฎ) for the treatment of **separation anxiety** when used in conjunction with a behavior modification plan. It is also used off-label for aggression, stereotypic behaviors (obsessive-compulsive disorders), and generalized anxiety. In cats, it is frequently prescribed for inappropriate elimination (urine marking), aggression, anxiety, and psychogenic alopecia/pruritus. > **Clinical Pearl:** Fluoxetine requires a significant lag time (typically **4 to 8 weeks**) before full clinical efficacy is observed. This is due to the time required for postsynaptic receptor downregulation. Owners must be counseled to remain patient and compliant during this initial period.
Mechanism: Fluoxetine acts by selectively binding to and inhibiting the presynaptic **serotonin transporter (SERT)** in the central nervous system. * **Inhibition of Reuptake:** Blockade of SERT prevents the reuptake of serotonin (5-HT) into the presynaptic neuron. * **Increased Synaptic Serotonin:** This leads to an accumulation of serotonin in the synaptic cleft โ prolonged activation of postsynaptic **5-HT receptors**. * **Receptor Downregulation:** Chronic elevation of synaptic serotonin eventually leads to the downregulation and desensitization of autoreceptors (e.g., 5-HT1A), which correlates with the onset of anxiolytic, anticompulsive, and anti-aggressive clinical effects. Fluoxetine has minimal affinity for other neurotransmitter receptors (such as dopamine, norepinephrine, histamine, or acetylcholine), which accounts for its relatively favorable side effect profile compared to tricyclic antidepressants (TCAs).
Dosing by species
- Adjunctive treatment of aggression ยท 0.5-1.5 mg/kg PO once daily ยท PO ยท q24h
- To help control urine marking or separation anxiety ยท 0.5-1 mg/kg (2.55 mg per cat) PO once daily ยท PO ยท q24h
- To control pruritus when other therapies have failed ยท 1-5 mg/cat PO once daily ยท PO ยท q24h ยท Assess therapy after 1-4 weeks. Taper off dose over 6-8 weeks. ยท Advise obtaining baseline lab work.
- Generalized anxiety disorder ยท 0.5-1.5 mg/kg PO once daily ยท PO ยท q24h
- Urine spraying, psychogenic alopecia, and aggression ยท 0.5-1.0 mg/kg ยท PO ยท q24h ยท Long-term as directed ยท Similar precautions for aggression apply as in dogs.
- Treatment of canine separation anxiety in conjunction with a behavior modification plan ยท 1-2 mg/kg PO once daily ยท PO ยท q24h
- Separation anxiety and noise aversions ยท 1-2 mg/kg PO once daily ยท PO ยท q24h ยท Continue until 2 months after satisfactory response, then discontinue gradually ยท Use with behavioral therapy. May use long-term. Some dogs require life-long treatment. May add a benzodiazepine during seasonal noise fears.
- Adjunctive pharmacological intervention for conflict-related aggression ยท 1-2 mg/kg PO once a day ยท PO ยท q24h ยท May take up to 4 weeks for efficacy.
- Compulsive disorders ยท 1-2 mg/kg PO once daily ยท PO ยท q24h
Routes of administration
Contraindications
- Known hypersensitivity to fluoxetine
- Concurrent use of Monoamine Oxidase Inhibitors (MAOIs), including selegiline and amitraz (found in some tick collars)
- Patients with epilepsy or a history of seizures
- Concurrent use with drugs that lower the seizure threshold (e.g., acepromazine, chlorpromazine)
- Known sensitivity to fluoxetine or other SSRIs
- History of seizures or epilepsy
Adverse effects
- Anorexia or decreased appetite (common, often transient)
- Lethargy or depression
- Gastrointestinal upset (vomiting, diarrhea)
- Anxiety, irritability, or restlessness
- Insomnia or hyperactivity
- Panting (dogs)
- Changes in elimination patterns (cats)
- Paradoxical aggressive behavior (in previously unaggressive animals)
- Seizures (rare but possible)
- Lethargy
- Decreased appetite
- Vomiting
- Weight loss
- Trembling
- Restlessness
- Gastrointestinal disturbances
Drug interactions
- BUSPIRONE ยท Increased risk for serotonin syndrome
- CYPROHEPTADINE ยท May decrease or reverse the effects of SSRIs (acts as a serotonin antagonist)
- DIAZEPAM, ALPRAZOLAM ยท Fluoxetine may increase diazepam and alprazolam plasma levels
- DIURETICS ยท Increased risk for hyponatremia
- INSULIN ยท May alter insulin requirements (can alter blood glucose)
- ISONIAZID ยท Increased risk for serotonin syndrome
- MAO INHIBITORS (e.g., amitraz, selegiline) ยท High risk for serotonin syndrome; use contraindicated. A 5-week washout is required after stopping fluoxetine before starting an MAOI, and a 2-week washout if switching from an MAOI to fluoxetine.
- PENTAZOCINE ยท Serotonin syndrome-like adverse effects possible
- PHENYTOIN ยท Increased plasma levels of phenytoin possible
- PROPRANOLOL, METOPROLOL ยท Fluoxetine may increase these beta-blocker's plasma levels; atenolol may be safer to use
- TRAMADOL ยท SSRIs can inhibit the metabolism of tramadol to active metabolites, decreasing efficacy and increasing toxicity risk (serotonin syndrome, seizures)
- TRICYCLIC ANTIDEPRESSANTS (e.g., clomipramine, amitriptyline) ยท Fluoxetine may increase TCA blood levels and increase the risk for serotonin syndrome
Monitoring
- Efficacy of the behavior modification plan and reduction of clinical signs
- Appetite and body weight (due to risk of anorexia)
- Signs of adverse effects (GI upset, lethargy, paradoxical aggression, seizures)
- Behavioral response and changes in aggression
- Appetite and body weight
- Signs of serotonin syndrome (tremors, agitation, hyperthermia)
- Gastrointestinal tolerance
Overdose
The LD50 for rats is 452 mg/kg. **Clinical Signs of Toxicity:** * **Dogs:** Vomiting, mydriasis (dilated pupils), lethargy, hyperactivity, and seizures. Seizures have been reported at doses twice the highest recommended human dose. * **Cats:** Hypersalivation, vomiting, mydriasis, and excessive vocalization. **Treatment:** * Treatment is symptomatic and supportive. * Gut emptying techniques (emesis, activated charcoal) should be employed if recent and not contraindicated (e.g., patient is seizing or comatose). * **Diazepam** is the treatment of choice for controlling seizures. * **Cyproheptadine** can be administered as a serotonin antagonist if serotonin syndrome is suspected.
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.