March 10, 2017

WVC 2017: Mirtazapine for Appetite Stimulation in Cats

This week at WVC 2017, Dr. Jessica Quimby outlined her research and experience with the tricyclic antidepressant mirtazapine in cats.
By Beth Thompson, VMD

UPDATE (JULY 10, 2018)—Mirataz, an FDA-approved transdermal ointment for the management of weight loss in cats, is now available for purchase to veterinarians in the United States. Developed by California-based Kindred Biosciences, this new ointment contains mirtazapine—a tetracyclic compound originally developed as an antidepressant for humans. Research on the use of mirtazapine in cats discovered its benefit as an appetite stimulant for felines experiencing unintended weight loss.

According to market research conducted by KindredBio, US veterinarians see as many as 9 million cats each year with unintended weight loss due to various conditions—making weight loss a leading cause of feline veterinary visits. 

Read the complete update.
Jessica Quimby, DVM, ACVIM, PhD, has a long-standing interest in chronic kidney disease in cats. Obviously, one of the issues in managing this disease is ensuring that patients eat. At the 2017 Western Veterinary Conference in Las Vegas, Nevada, Dr. Quimby spoke about the popularity and success of pharmacologic appetite stimulation with mirtazapine, provided tips to lessen side effects, and offered insight into research findings and the future of this drug.

From Human to Veterinary Medicine
Originally developed as a human antidepressant medication, mirtazapine is a tetracyclic compound whose mechanism of action is largely unknown. Although successful as a human antidepressant, the drug has the unwanted yet significant and common side effect of appetite stimulation, which decreased its popularity as an antidepressant in people. However, because of that and its concurrent anti-nausea effect, the drug found a new niche in treating human cancer patients.

Mirtazapine’s introduction to veterinary medicine came via a physician who gave it to his dog as an appetite stimulant. Encouraged by that report, further work on 24 dogs and 17 cats yielded good to robust responses within 30 minutes in 25 of the test subjects. Cats displayed more side effects than did dogs, most notably pronounced vocalizations. An anecdotal dose of one-quarter of a 15-mg tablet every 72 hours was prescribed for cats based on the knowledge that the drug was glucuronidated in the liver and excreted through the kidneys.

Research Findings
The benefit of the drug was evident, but the side effect of what Dr. Quimby called the “kitty crazies” was detrimental. The most common side effects noted by the ASPCA Poison Control include vocalization, agitation, vomiting, ataxia, restlessness, trembling, and hypersalivation.1 Researchers like Dr. Quimby wondered whether the same positive results could be achieved and the side effects mitigated if the drug were given at a lower dose. Furthermore, so far, the test subjects had all been young, healthy cats, yet the drug was wanted for use in older, chronically ill cats. Would there be a difference in onset, duration, and excretion of the drug in those patients? Finally, would the accepted every-3-day dosing in cats give the best results with the fewest side effects?
Results of a 2011 study led by Dr. Quimby2 suggested that the active appetite-stimulating effects of mirtazapine in young, healthy cats occur at a dose of one-eighth of a tablet (1.88 mg) versus the traditional higher dose of one-quarter of a tablet (3.75 mg). In their blinded trial, cats receiving mirtazapine consumed significantly more food than cats receiving placebo. However, there was no significant difference in appetite stimulation or calorie ingestion between cats given either dose. Fewer side effects were reported in the lower-dose group. What’s more, the half-life of the drug was 15.9 hours at the higher dose and 9.2 hours at the lower dose. Pharmacokinetics in the cat appear nonlinear, and metabolism may be slower at higher doses.

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