Clomipramine: The Treatment for Canine and Feline Separation Anxiety

What is clomipramine?

Clomipramine (Clomicalm®) is a tricyclic antidepressant that treats multiple psychological disorders in canines and feline species such as obsessive-compulsive disorder (OCD), depression, and anxiety. Clomipramine is FDA approved for the treatment of separation anxiety in canines greater than 6 months of age but used off-label for felines.

What is Separation Anxiety?

Separation anxiety is a complex behavioral disorder that affects about 20% to 40% of dogs, and can be displayed when the owner or attachment figure leaves. This is theorized to be because canines are naturally pack animals, and do not do well in solitary. Signs of this disorder can be observed via the presence of destructive behavior, excessive salivation, shaking, howling, and inappropriate elimination (urination or defecation). These symptoms resolve once animals are then reunited with their companion. Pets can have the potentiality of exhibiting one or more of these clinical signs. It is important to note that as an owner or attachment figure, understand that these signs of separation anxiety are a result of anxiety, not spite.

How Does Clomipramine Work?

This antidepressant works by mainly inhibiting the reuptake of serotonergic neurotransmitters as well as affecting the noradrenergic neurotransmitters within the central nervous system (CNS). By inhibiting the reuptake of serotonin this increases the amount of serotonin within the brain balancing your pets mood. Noradrenergic neurotransmitters are associated with blood pressure in our CNS, and clomipramine works by reducing blood pressure to achieve those calming/anti-anxiety effects. The use of clomipramine is not to replace appropriate behavioral and environmental management and is most effective in combination therapy.

How is Clomipramine Prescribed?

Clomipramine is a prescription medication sold in a variety of capsule dosages. The medication is weight based and often your pets breed and severity of condition is taken into consideration. Since this medication is an antidepressant it is important to wean your pet onto the full dose needed for best therapeutic effects. Beginning with the smallest dose, and increasing the dose over long intervals is best practice to reduce negative side effects. Talk to your veterinarian before discontinuing or altering your pets prescribed regimen.

Contraindications With Clomipramine

• Pets who have taken a monoamine oxidase inhibitor (eg. selegiline) within the last 14 days should not be given clomipramine.
• Pets who have used a Preventic tick collar in the last 14 days should not be given clomipramine.
• Animals with a known allergy to other tricyclic antidepressants (eg. imipramine, amitriptyline) should not be given clomipramine.
• Canines less than 6 months of age should not be given clomipramine.
• Clomipramine should not be given in animals with:
  • Liver disease, kidney disease, asthma, thyroid disease, diabetes, heart disease, stomach or intestinal problems, seizure disorders, pregnant and/or lactating, and are working dogs (eg. guide dogs).

Side Effects of Clomipramine

It is not unusual to see drowsiness or an increase in the effects of other medications your pet has been given when using clomipramine.

Efficacy of Clomipramine for Canines

Based on a 12 week study conducted in the United States, and Europe observed the efficacy of clomipramine tablets when treating anxiety among dogs. They found that tablets ranging from 2-4mg/kg/day divided twice daily in conjunction with behavioral and environmental modifications were shown to be more effective than behavior modification alone. This study results were reinforced when a 8 week study testing tablets for the treatment of anxiety of dogs was released. The study used the same dosage range as the last study and found that 47% of dogs on clomipramine one or twice daily in conjunction with behavioral and environmental modifications showed clinical improvements compared to the 29% of dogs receiving behavioral modifications alone.

FDA Approved Dosage and Administration for Canines

How is Clomipramine Supplied?

Clomipramine is commercially available in 5, 20, 40, and 80 mg tablet strengths in color-coded packaging to be orally administered to pets. These tablets are to be kept in a controlled temperature environment and out of reach from children.

Why Do We Compound Clomipramine?

Since the medication is commercially available in those fixed doses listed above, it can be difficult matching the exact dose needed for certain patients. Clomipramine is a weight based medication which means some pets may require a lower or higher dose than those commercially available. Being able to compound this medication at a specialty pharmacy allows for more precise dosing with alternate dosage forms and flavors. Individualized patient care can be effectively maintained through compounding.

References:

1. PubChem [Internet]. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2004-. PubChem Compound Summary for CID 2801, Clomipramine; [cited 2022 Aug. 9]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Clomipramine
2. Frank D, Gauthier A, Bergeron R. Placebo-controlled double-blind clomipramine trial for the treatment of anxiety or fear in beagles during ground transport. Can Vet J. 2006 Nov;47(11):1102-8.
3. Clomicalm - FDA prescribing information, side effects and uses
4. Clomipramine For Dogs With Canine Anxiety
5. Clomipramine | VCA Animal Hospital
6. https://www.mspca.org/wp-content/uploads/2017/04/Plumbs-Clomipramine.pdf
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