Fluoxetine

Mechanism of Action

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) which functions by inhibiting the reuptake of serotonin in the pre-synaptic neuron.

Fluoxetine is largely metabolised in the liver by the cytochrome P450 enzyme system to norfluoxetine, also an SSRI.

Uses

• Licensed [dog]

• Treatment of canine separation anxiety in conjunction with behaviour modification in dogs over 6 months old.

• Unlicensed

Fluoxetine is not recommended for treatment of aggression.

Due to the long half-life of fluoxetine it is not necessary to gradually reduce or taper the dose. Once treatment with fluoxetine has ceased continued behavioural modification is advisable to avoid the reappearance of clinical signs. The long half-life of fluoxetine and its metabolites also mean that a period of at least 6 weeks should be allowed to pass before administration of any drugs which may interact adversely.

Adverse Effects

• Decreased appetite
• Depression/lethargy
• Shaking/shivering/tremor
• Vomiting and diarrhoea
• Restlessness and anxiety
• Seizures
• Aggression
• Mydriasis
• Vocalisation
• Weight loss
• Panting
• Confusion
• Incoordination
• Hypersalivation

Caution should be taken in if the animal suffers from any of the following pre-existing medical conditions:

• Contraindicated for animals with a history of epilepsy or seizures

Care should be taken if used in conjunction with any of the following drugs, which may interact and cause adverse effects:

• Fluoxetine should not be given at the same time as drugs which lower seizure threshold eg. phenothiazines such as acepromazine or chlorpromazine.
• Monoamine oxidase inhibitors (MAOI), or within a period of 2 weeks after discontinuation of treatment with a MAOI.
• Fluoxetine has not been evaluated with drugs that affect the cytochrome P450 enzyme, care should therefore be taken with any drug that affects the enzyme system eg. ketoconazole.