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

 
In that same study, Dr. Quimby and her team compared the drug’s action in normal young cats versus healthy old cats. Results for both groups showed equally useful appetite-stimulation effects at the lower dose and more side effects at the higher dose. As with humans, clearance of the drug is affected by disease state. The human data show that with moderate kidney disease, clearance is decreased by 33%. That rises to 50% in severe kidney disease. In patients with liver disease, one can expect a 33% reduction in clearance. The half-life of mirtazapine increased to 15 hours in cats with chronic renal failure. Research is currently under way to determine the effects of feline liver disease on drug clearance.
 
In a placebo-controlled, double-masked clinical trial of 16 cats with chronic kidney disease and no comorbidities, cats were given either mirtazapine dosed at 1.87 mg every other day or a placebo for 3 weeks.3 The cats were then "washed out" for 4 days and placed in the other group for an additional 3 weeks. The owners kept daily logs, and cats were routinely examined, weighed, and body condition scored. Eleven cats completed the study. Of those, 91% of mirtazapine cats gained weight and 71% had improved body condition scores, while 82% of cats lost weight when taking the placebo. There was a significant (P = .002) increase in appetite in the cats treated with mirtazapine.
 
Dosing
Veterinarians should be careful about mirtazapine toxicity. It does occur—and is most often due to a misunderstanding about dividing the pill. Dr. Quimby suggests dispensing exact of doses of mirtazapine to reduce accidental administration of a full tablet (15 mg) and resultant toxicity.
Dr. Quimby expressed enthusiasm for transdermal mirtazapine administration. Citing a 2016 study published in the Journal of Feline Medicine and Surgery,4 she noted that even though drug concentration in the compounded preparation can vary up to 10% and that drug absorption is reduced when administered through the skin instead of orally, transdermal delivery results in easier administration and more constant blood concentration. That steady blood level appears to reduce side effects. With proper compounding, transdermal application achieves sufficient serum concentration and stimulates appetite in healthy cats. As with other transdermal medications, the strength needs to be a higher to achieve the same blood levels. A 7.5-mg transdermal dose has been shown to be effective, but studies are under way to determine if a lower dose will be equally effective. Dr. Quimby reminded the audience how essential it is to wipe off the previous dose from the inner pinna before giving the next one to avoid drug accumulation.
 
Summary
In conclusion, mirtazapine works as an appetite stimulant in cats. Current dosing recommendations for mirtazapine in young, healthy cats is 1.88 mg/day. In older cats and those with chronic kidney or liver disease, 1.88 mg can be given every 48 hours. This dose, while effective, results in fewer undesirable side effects than the traditional 3.75-mg dose. Transdermal preparations are easier to administer and work well when compounded correctly. We look forward to commercially available transdermal preparations in the future.
 
Dr. Thompson is a small animal veterinarian, animal health executive, editor, and writer. She has held numerous positions with oversight responsibilities for editorial and business direction, including for Veterinary Learning Systems (publisher of Veterinary Technician and Compendium), Vetstreet.com, HealthyPet, and NAVC. 
References:
  1. Ferguson LE, Mclean MK, Bates JA, Quimby JM. Mirtazapine toxicity in cats: retrospective study of 84 cases (2006-2011). J Feline Med Surg. 2015;Jul 30;pii. 1098612X15599026. [Epub ahead of print]
  2. Quimby JM, Gustafson DL, Lunn KF. The pharmacokinetics of mirtazapine in cats with chronic kidney disease and in age-matched control cats. J Vet Intern Med. 2011;25(5):985-989.
  3. Quimby JM, Lunn KF. Mirtazapine as an appetite stimulant and anti-emetic in cats with chronic kidney disease: a masked placebo-controlled crossover clinical trial. Vet J. 2013;197(3):651-655.
  4. Benson KK, Zajic LB, Morgan P, et al. Drug exposure and clinical effect of transdermal mirtazapine in healthy young cats: a pilot study. J Fel Med Surg. 2016;Sept 9:pii: 1098612X16667168.


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