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Fluoxetine for Dogs and Cats

By Barbara Forney, VMD

Last reviewed: 7/13/2022

Commonly prescribed for: Separation Anxiety; Aggression; OCD

Species: Dogs and Cats

Therapeutic Class: SSRI

Basic Information

Fluoxetine is an SSRI.  Fluoxetine increases serotonin levels within the central nervous system by preventing the re-uptake of serotonin at the level of the presynaptic neuron. This allows serotonin to accumulate in the synaptic cleft and affect the post-synaptic neuron. Serotonin is the neurotransmitter responsible for facilitating social interactions, general awareness, coping mechanism, and adaptability. SSRI drugs commonly are prescribed for humans as a part of the treatment of depression, anxiety disorders, compulsive disorders, and difficulty managing aggression. Fluoxetine must be administered for four to eight weeks before the full effect on serotonin levels is realized.

Fluoxetine is well-absorbed orally. Although the bioavailability of transdermal fluoxetine is only about 10% of that of the oral medication, it may be an alternative when oral administration is not feasible or safe.

Dogs and Cats

Fluoxetine is FDA-approved for use in separation anxiety in dogs. All other uses of fluoxetine in dogs and cats are extra-label but there is considerable literature and experience on the use of SSRI's for small-animal behavior problems. In addition to the use of medication, much of the behavior literature stresses the importance of behavior modification training, owner training, and addressing environmental issues as cornerstones of successful therapy.

Fluoxetine is useful to treat some but not all forms of aggression in dogs. It is used for inter-dog aggression in conjunction with behavioral training and neutering of the less dominant dog. Fluoxetine also is used to treat obsessive compulsive disorders in dogs. Specific phobias such as fear of storms usually are treated by benzodiazepines because of their episodic nature and the drug's rapid onset of action. There are instances when combining a SSRI and a benzodiazepine are warranted because of the need for a brief period of increased anxiolytic, such as the first half hour of separation for a dog with marked separation-anxiety.

Indoor cats appear to be susceptible to anxiety disorders due to their lack of social skills and the importance of territorial organization. Manifestations of anxiety in cats may include inappropriate elimination, aggression, obsessive compulsive behavior, hyperactivity, or hypervigilance. Fluoxetine may be helpful for cohabitation anxiety, closed surrounding anxiety, and territory related anxiety. Because of the high rate of recidivism in cats that urine spray, fluoxetine therapy may need to be continued for a month or two after the resolution of the spraying problem.

Fluoxetine Side Effects

  • Dogs: Sedation and anorexia are the most-commonly reported side effects. Other side-effects include GI upset and behavior changes (anxiety, irritability, hyperactivity, and insomnia). Aggression (very uncommon) and seizures also have been reported.
  • Cats: Anorexia and behavior changes (anxiety, irritability, hyperactivity/insomnia, and elimination behavior) are the most-commonly reported side effects in cats. Anorexia is a common-enough side effect in the cat that the client should monitor the cat's appetite and weight. Dermatitis may occur at the site of transdermal application.


  • Serotonin syndrome is a potentially life-threatening, iatrogenic drug-reaction caused by excessive intra-synaptic serotonin. It is very rare in animals but may occur when multiple serotonergic drugs are administered, with an overdose or in instances of individual hypersensitivity. This most-commonly occurs with a combination of SSRI and MAOI medications, although there are some opioid analgesics with serotonergic activity. Symptoms include neuromuscular hyperactivity, hyperthermia, autonomic hyperactivity, and altered mental status.
  • Fluoxetine usually is not prescribed for animals with diabetes mellitus or seizure disorders. Animals with impaired liver function may need reduced a dose.
  • There are active metabolites of fluoxetine for four to five weeks after discontinuing the drug.
  • Some animals appear to stop responding to an individual SSRI medication. This also occurs in humans but it has not been studied widely in dogs and cats.

Drug Interactions

  • There are many potential or hypothetical drug interactions for fluoxetine in dogs and cats although many of these are extrapolated from experience in humans.
  • The list of potential drug interactions includes; acepromazine, amitraz (including the flea/tick collars and dips) buspirone, cyproheptadine, diazepam, alprazolam, diuretics, insulin, isoniazid, MAO inhibitors (selegiline), pentazocine, phenytoin, propanolol, metoprolol, tramadol, tricyclic antidepressants, trazodone, and warfarin.


  • Signs of overdose in dogs and cats resemble those discussed under side effects: lethargy, hyper salivation, agitation. Seizures may occur in dogs that have received a massive overdose.
  • Fluoxetine is well-absorbed orally and signs of overdose may present in 30 to 60 minutes. If an overdose is recognized promptly, emesis and gastric lavage should be attempted in the conscious animal. Activated charcoal and cathartics may be used subsequently as warranted by clinical signs. Diazepam should be used in animals that are seizuring. Although IV fluids will not enhance drug excretion they may be indicated to support blood pressure, renal function, and aid in thermoregulation.
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