Clomipramine

(for veterinary information only)

BRAND NAME: CLOMICALM, ANAFRANIL

AVAILABLE IN       
5 mg, 20 mg, 40 mg, 80 mg
TABLETS            
approved for veterinary use

25 mg, 50 mg, 75 mg    
CAPSULES           
for human use          

BACKGROUND

Not surprisingly, there is a very large market for medications used in the treatment of anxiety disorders in people. People want to be free from worry and stress without suffering drowsiness, addiction, or any other untoward side effects. In earlier times, the benzodiazepine family of drugs (of which Valium® is a member) were the predominant anxiety medications but their use was complicated by sedative side effects and chemical dependence. These unacceptable side effects drove researchers to seek a better solution. The tricyclic antidepressants, so named for their chemical structure, represent the results of these efforts.

clomipramine

chemical structure of clomipramine

Of course, anxiety is not a problem exclusive to humans. Many pets have anxiety about separation from their owner, about aggressive pets with whom they share their home, about loud noises such as thunderstorms, and about other issues. The medications used to help animals with these issues are the same medications that humans use. Clomipramine is the first to achieve FDA approval for use in dogs as well as humans.

The precise mechanism of action (i.e., exactly how these drugs work) is not known fully but it is believed that they act by increasing the activity of the neurotransmitter serotonin in the brain. Clomipramine is classified as a "tricyclic" antidepressant (because of its 3 ring chemical structure as shown above) and affects several neurotransmitters including serotonin. Serotonin, in simple terms, is associated with the cozy, happy feelings of comfort. Clomipramine inhibits the removal of serotonin in the brain so that the serotonin present is present for a longer time.

HOW THIS MEDICATION IS USED

While clomipramine is only approved for use in humans and dogs, it is also widely used in cats. It helpful in treating:

SIDE EFFECTS

Clomipramine has what are called anticholinergic side effects. This means that clomipramine inhibits the involuntary functions mediated by the neurotransmitter acetylcholine. These are not usually significant but the list of anticholinergic side effects to watch for includes:

  • Retention of urine/difficulty passing urine
     
  • Reduced intestinal motility
     
  • Increased eye pressure
     
  • Heart rhythm disturbance (especially in patients with unregulated hyperthyroidism or taking thyroid supplementation)

Other side effects reported include: vomiting, diarrhea,sedation, and dry mouth (which might manifest as increased water consumption), and dry mouth (which might manifest as increased water consumption).

INTERACTIONS WITH OTHER DRUGS

Clomipramine is incompatible with monoamine oxidase inhibitors. Monoamine oxidase inhibitors have very few veterinary uses where this is likely to be an issue but there are two situations where this drug interaction might be relevant. Clomipramine could pose a problem with amitraz-containing tick or mite control products(the Preventic® collar Certifect® topical, or Mitaban® dips) as amitraz is a monoamine oxidase inhibitor. The other monoamine oxidase inhibitor used for animals is selegiline which is used to treat cognitive dysfunction (senility) and sometimes is used for in the treatment of Cushing's disease. The drug interaction with clomipramine could result in a condition called "serotonin syndrome" which features extreme high blood pressure. Other medications that can increase the risk for serotonin syndrome include: meperidine (pain reliever), pentazocine (pain reliever), fluoxetine (another anxiety medication), and dextromethorphan (cough suppressant).

Anti-thyroid medications such as methimazole carry a risk of blood dyscrasias meaning that some blood cell lines may be suppressed. When these drugs are used in combination with clomipramine the risk of this side effect is increased.

Cimetidine (Tagamet®) may slow the removal of clomipramine, effectively increasing the potential to reach a toxic blood level.

Using clomipramine with other drugs that have anticholinergic side effects (as reviewed above) increase the chances of seeing those side effects. Such other drugs include most antihistamines.

Using clomipramine with cisapride (a constipation drug) can lead to heart rhythm abnormalities.

CONCERNS AND CAUTIONS

Several weeks of use are needed before one may expect to see a therapeutic effect.

  • Clomipramine should not be used in patients with seizure disorders as it may facilitate seizures.
     
  • Clomipramine may affect male fertility but does not seem to cause trouble when used during pregnancy.
     
  • Clomipramine may exacerbate glaucoma.

It does not matter if this medication is taken with food or not. It is well absorbed from the intestinal tract either way.

  • Clomipramine definitely crosses into the milk of nursing mothers.
     
  • An overdose of approximately 12 times the recommended dose is often lethal.
     
  • Tricyclic antidepressants may alter blood glucose levels.
     
  • In a 2003 study published in the Journal of Veterinary Internal Medicine, it was found that clomipramine lowered thyroid test values in at least 35% of patients. These dogs were not believed to actually have hypothyroidism; results were interpreted to mean that a dog on clomipramine could be erroneously diagnosed as hypothyroid.

The canine version of clomipramine (Clomicalm®) is manufactured by Novartis Animal Health. Their web page detailing this product and including the actual product insert is at:

www.clomicalm.novartis.us/pdf/Clomicalm-product-info.pdf

Page last updated: 3/19/2013