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By Wendy C. Brooks, DVM, DipABVP
Educational Director,

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Clomipramine (Clomicalm, Anafranil)

Brand Name: Clomicalm, Anafranil

Available in 5 mg, 20 mg, 80 mg tablets approved for veterinary use; available in 25 mg, 50 mg, 75 mg capsules for human use


Not surprisingly, there is a large market for medications to treat anxiety disorders in people. People want to be free from worry and stress without suffering drowsiness, addiction, or any other untoward side effects. It used to be that 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.

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 other issues. The medications used to help animals with these issues are some of the same ones 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 (so-named for its three-ring chemical structure) 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 that is there 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:

Clomipramine is given once or twice daily and may be given with or without food. If nausea is felt to be an issue, a small amount of food given with it may be all that is needed to relieve this problem. 

If a dose is skipped, do not double up on the next dose; simply pick up where the dose was left off.  

Store clomipramine capsules and tablets at room temperature, protected from light.

Side Effects

The most common side effect likely to be seen is sedation. This is generally managed by adjusting the dose.

Clomipramine has potential to produce 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 that could become of concern includes:

  • Retention of urine/difficulty passing urine (watch for straining to urinate)
  • Reduced intestinal motility (watch for vomiting, drooling, appetite loss)
  • Increased eye pressure (watch for eye pain, dilated pupils)
  • Heart rhythm disturbance (especially in patients with unregulated hyperthyroidism or taking thyroid supplementation)

Other side effects reported include: vomiting, diarrhea, and dry mouth (which might be seen as increased water drinking).

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 for Cushing's disease. The drug interaction with clomipramine could result in a condition called serotonin syndrome that features extreme high blood pressure. Other medications that can increase the risk for serotonin syndrome include: meperidine (pain reliever), pentazocine (pain reliever), tramadol  (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) increases 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.

Additional medications that can combine with clomipramine to increase the chance of an abnormal heart rhythm are: trazodone (a short-acting tranquilizer), metronidazole (commonly used to treat diarrhea), "azole" anti fungal medicines (ketoconazole, itraconazole, fluconazole, etc.) and macrolide antibiotics (azithromycin, tylosin, erythromycin).

Concerns and Cautions

Several weeks of use are needed before a therapeutic effect is seen. Up to 2 months may be needed to determine if clomipramine is helpful to a given patient.

  • Clomipramine should not be used in patients with seizure disorders as it may help create seizures.
  • Clomipramine may affect male fertility but does not seem to cause trouble when used during pregnancy.
  • Clomipramine may exacerbate glaucoma and may exacerbate heart rhythm abnormalities though its anticholinergic side effects described above.
  • It doesn't 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, clomipramine was found to lower 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.
  • Clomipramine is activated in the liver. It is removed from the body via the kidneys as well as the liver. Patients with liver disease may not metabolize this drug predictably.

It is our policy not to give dosing information over the Internet.


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