Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

ANTIDEPRESSANTS
In dogs, fluoxetine and sertraline have been used in
the treatment of acral lick granulomas. Fluoxetine has
also been used to treat obsessive-compulsive disorders,
separation anxiety, generalized anxiety or global fear
and dominance aggression. Paroxetine has also been
used to treat generalized anxiety disorder with 50% of
patients showing clinical improvement. Citalopram has
been used to treat acral lick dermatitis with a satisfactory
result being seen in about 2 weeks. Until recently,
their high cost generally prevented SSRIs from being the
drug of first choice in companion animal therapy.
However, fluoxetine is now off patent and the generic
forms are more affordable. They and other SSRIs are a
valuable therapeutic option if the owner’s financial constraints
do not preclude their use. However, the mintflavored
liquid formulation is not readily accepted by
some cats.
Mechanism of action
Selective serotonin reuptake inhibitors selectively inhibit
serotonin reuptake in presynaptic neurones in the CNS.
The therapeutic effect of SSRIs in obsessive-compulsive
disorders is thought to be mediated by disinhibition of
serotonin neurones in the pathway from the midbrain
raphe to the basal ganglia. Similarly, the amelioration
of panic disorders is thought to occur when disinhibition
of the pathway to the limbic cortex and hippocampus
occurs. However, activation of serotonin receptors
can worsen panic or anxiety initially. This has been
observed in both humans and companion animals.
Formulations and dose rates
DOGS
Fluoxetine
• 1–2 mg/kg PO q.24 h
Fluvoxamine
• 0.5–2 mg/kg PO q.24 h (up to 4 mg/kg q.12 h if necessary,
increased incrementally)
Paroxetine
• 1 mg/kg q.24 h
Sertraline
• 1–3 mg/kg PO q.24 h
Citalopram
• 0.5–1 mg/kg q.24 h
CATS
Fluoxetine
• 0.5–1 mg/kg PO q. 24 h
Fluvoxamine
• 0.25–0.5 mg/kg PO q.24 h (up to 1–2 mg/kg q.12 h; increase
incrementally)
Paroxetine
• 0.5–1 mg/kg PO q.24 h
Sertraline
• 0.5–1 mg/kg PO q.24 h
BIRDS
Fluoxetine
• 2.0–5.0 mg/day
Pharmacokinetics
Fluoxetine is well absorbed after oral administration,
with peak plasma concentrations in humans achieved in
4–8 h. In a study in beagles, bioavailability was 70%.
The presence of food alters the rate but not extent of
absorption. Fluoxetine is highly protein bound (95%)
in humans. It has been administered transdermally to
cats. However, the relative bioavailability by this route
was only 10% of that achieved after oral administration;
the study did not determine the actual oral bioavailability
in cats.
Fluoxetine and its major metabolite are distributed
throughout the body, with highest levels found in lung
and liver. CNS concentrations are detected 1 h after
dosing. Fluoxetine is metabolized in the liver to a variety
of metabolites. The demethylated active metabolite,
norfluoxetine, has a half-life of 7–9 d at steady state,
while the parent drug has a shorter half-life of 2–3 d. In
humans, there is wide interpatient variation in duration
of action. Liver, but not renal, impairment will increase
clearance times.
Sertraline and paroxetine have similar pharmacokinetic
parameters to the TCAs.
Adverse effects
● Mild sedation.
● Transient decreased appetite.
● Increased anxiety.
● Decreased sexual motivation in animals and
humans.
● Nausea, lethargy, weight loss, tremors and
agitation have been reported in humans.
● In humans increased liver enzymes may occur,
although there are no reports of liver pathology
unless the patient had prior liver disease.
● Gastrointestinal disturbances such as vomiting or
diarrhea have been reported in humans.
● Drug-induced rashes have been reported in
humans.
Known drug interactions
● Fluoxetine can increase the half-life of concurrently
administered diazepam, although in the short term
the drug combination is recommended for humans
by some psychiatrists.
● Concomitant MAOI therapy can cause a serotonin
syndrome. This is a very serious condition characterized
by changes in mental status, hyperthermia,
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