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New Generic Med for Separation Anxiety — Should You Use It?

Analysis by Dr. Karen Shaw Becker Fact Checked

treating separation anxiety in dogs

Story at-a-glance -

  • A drug used to treat separation anxiety in dogs is now available as a generic, making it more affordable for more pet parents
  • If your dog suffers from separation anxiety and your veterinarian suggests clomipramine, it’s very important to research this powerful drug to determine if it’s the best option for your pet
  • Clomipramine can induce multiple side effects, shouldn’t be taken with a wide variety of other veterinary drugs, and carries several other cautions as well
  • All cases of separation anxiety should be managed with behavior modification as the foundation of the protocol, with drugs or nutraceuticals being used adjunctively, as needed
  • Before you agree to give behavior-modifying drugs to your pet, I encourage you exhaust nontoxic options first

If you require a prescription medication for a chronic condition, for example, asthma or migraine headaches, you're probably familiar with the difference in cost between branded and generic drugs. Whenever a very expensive name brand medication finally becomes available in generic form, the cost plummets, and many people who need it breathe a sigh of relief.

All of you who read here regularly know I prefer to avoid pharmaceuticals for pets (and people) when effective, nontoxic solutions exist, but I also understand the importance of affordable prescriptions for those who need them.

However, it's important to note that one concern with all generic medications is that manufacturers aren't required to prove safety or efficacy, only that the generics contain the active ingredients used in the brand name drugs. And in the case of psychotropic medications, both psychiatrists and veterinary animal behaviorists frequently find that a patient's response to a generic differs from his or her response to the original branded drug.1

With all that said, today I want to discuss a drug for separation anxiety in dogs that is now available in generic form. It's grabbing headlines in both veterinary publications and the mainstream media,2 which tells me many of you may be offered this medication by conventional veterinarians if your dog has separation anxiety.

Despite the relative affordability of this new generic, there are many other factors to consider if you're thinking of giving this drug to a furry family member.

Clomipramine Hydrochloride

The branded veterinary drug is Clomicalm, which has been around for about 20 years. The generic recently approved by the FDA is clomipramine hydrochloride, usually referred to simply as clomipramine. Per, the drug is to be used "as part of a comprehensive behavioral management program to treat separation anxiety in dogs greater than 6 months of age."3

Experts estimate that separation anxiety affects from 20% to 40% of dogs whose owners seek out veterinary behavior specialists.4 Clomipramine is a tricyclic antidepressant, and while we still don't know exactly how the drug works, it is thought to increase the activity of the neurotransmitter serotonin in the brain.

Serotonin increases feelings of comfort and happiness, and clomipramine inhibits the removal of serotonin in the brain so that it remains there for a longer time.

According to the website Veterinary Partner, while only approved for use in humans and dogs, clomipramine is also used widely in cats. Conditions the drug is often prescribed for include separation anxiety and other forms of anxiety, feline inappropriate urination, compulsive disorders, and dominance aggression.5

Side Effects and Interactions with Other Drugs

The most frequently reported side effect of clomipramine is sedation. Others include vomiting, diarrhea, and dry mouth. More importantly, this drug can produce anticholinergic side effects (meaning it can inhibit involuntary functions mediated by the neurotransmitter acetylcholine) including:

  • Heart rhythm disturbance, especially in hyperthyroid pets
  • Difficulty passing urine/retention of urine
  • Reduced intestinal motility
  • Increased eye pressure

Clomipramine can interact with flea/tick control products containing amitraz, a monoamine oxidase inhibitor. Amy Brannan, a dog parent who writes for the Canine Journal, tells of her experience giving both clomipramine and Frontline Plus (a flea and tick preventive containing amitraz) to her 10-year-old black Lab, Jet, who has a long history of unexplained anxiety.

"A month after we [began] a regular dosage of clomipramine, Jet was taking one pill in the morning and one at night. I had yet to see any signs of improvement in his anxiety symptoms. We scheduled a blood draw with our vet and on the same day picked up Frontline Plus flea and tick preventative.

Jet has been on Frontline since he was a youngster but this time something went wrong. Our vet called it an 'unseen reaction between clomipramine and Frontline Plus' — a reaction that overnight turned the application site on his neck blood-red and caused itching and hair loss in significant clumps.

Upon treatment our vet gave us the option to continue clomipramine for another few weeks to see if we saw any improvement in anxiety, [which] I rejected.

We are now weaning Jet off clomipramine and treating the freshly shaved patch on the back of his neck with antibiotics and steroids. Our search for the perfect anti-anxiety solution is still underway."6

This is an all-too-common example of the snowball effect that can occur with the casual, indiscriminate use of veterinary pharmaceuticals (in this case including a pesticide — Frontline), and poor Jet paid the price.

The clomipramine may or may not have been the best option for the dog's anxiety, but it wasn't effective in any event. In my opinion, the Frontline shouldn't have been given on top of the clomipramine (if at all), and my guess is the problem with his neck could have been successfully resolved without resorting to the use of two additional chemicals (antibiotics and steroids) that come with their own long list of serious side effects.

Clomipramine also shouldn't be given to animals receiving selegiline — another monoamine oxidase inhibitor — to treat cognitive dysfunction or Cushing's disease. The interaction of these drugs and clomipramine can result in serotonin syndrome, a condition characterized by extremely high blood pressure.

Clomipramine also shouldn't be given to animals taking anti-thyroid medications such as methimazole, cimetidine (Tagamet), most antihistamines, cisapride (a constipation drug), trazodone, metronidazole, "azole" antifungals (ketoconazole, itraconazole, fluconazole, etc.) and macrolide antibiotics (azithromycin, tylosin, erythromycin).

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Additional Cautions and Concerns Regarding Clomipramine

From Veterinary Partner:7

It takes several weeks before the drug's therapeutic effect is seen, and it can take up to 2 months to determine if it is helping alleviate a dog's separation anxiety

It shouldn't be used in pets with seizure disorders as it may actually trigger seizures

It may affect male fertility, and while it doesn't appear to cause problems in pregnant females, I would certainly recommend not using it during pregnancy; it definitely crosses into the milk of nursing mothers

It may exacerbate glaucoma and heart rhythm abnormalities due to its anticholinergic side effects

An overdose of approximately 12 times the recommended dose is often lethal

It may alter blood glucose levels

It is activated in the liver and removed from the body via the kidneys as well as the liver; pets with liver disease may not metabolize the drug normally

In a 2003 study, 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 hypothyroid8

My Recommendation: Consider All Other Options First

Given the side effects, drug interactions, and other concerns regarding clomipramine, it certainly wouldn't be the first thing I'd reach for to help dogs with separation anxiety, and I strongly urge you to consider other options as well, beginning with behavior modification.

In my opinion, scripting out mind-altering drugs without addressing the destructive, repetitive behavior patterns characteristic of separation anxiety isn't serving our anxiety-ridden patients at all. The minute you see your pet have even a mild stress response when left alone, it's time to begin actively addressing the issue with focused behavior modification.

Because so many vets don't receive training to effectively address behavior problems and because they typically don't ask about behavior changes at exams, in general our profession fails to institute effective behavior modification early on, when repatterning is easiest. I recommend you find a positive trainer immediately, if this is your situation.

If your canine companion, like so many others, suffers from this life-altering condition, my recommendation is to search this site first, where you'll find a wealth of information on what separation anxiety is and how it affects your pet's quality of life. More importantly, you'll also find lots of recommendations and tips for alleviating your dog's anxiety through a wide variety of natural remedies and therapies.

A good place to start is with my most recent article on the topic, Mistakes Dog Owners Make About Separation Anxiety.