The Anorexic Cat: A Breakdown of Appetite Stimulants

Encouraging some cats to eat can seem like a never ending battle. Learn from Ladan Mohammad-Zadeh, DVM, DACVECC, about a few of the best practices and medications available on the market.

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We’ve all encountered the frustration that is the anorexic cat. It is possible to run a comprehensive diagnostic panel and still not understand why the patient is not eating. Add full body imaging and your client can easily spend quite a bit of money without a definitive diagnosis. In some instances, you may diagnose pancreatitis or other nonsurgical condition, which leaves you with only medical management options. The gold standard for nutritional intervention in a cat with no vomiting or only occasional vomiting would be a feeding tube. An esophagostomy tube for home use or nasogastric or nasoesophageal tubes for in-hospital use are examples of commonly placed tubes for assisted nutrition. Unfortunately there may be cost barriers or other barriers to placing a feeding tube. Some clients associate feeding tubes with end-of-life care as is often the case in humans. However, our experience in veterinary medicine is that most feeding tubes are meant for temporary use. We also tend to carry a more optimistic outlook regarding the patients’ return to voluntary food intake.

Outside of assisted nutrition, other medical strategies to combat anorexia are aimed at treating the underlying disease; improving the cat’s symptoms, pain, nausea and dehydration; and improving their appetite. We are pharmacologically limited on medications to actually stimulate appetite, but there are some options. Unlike many medications that have reliable efficacy for their intended use (antimicrobials, analgesics), the entire category of appetite stimulants and efficacy is a gray zone. Fortunately, very few of these medications come with significant side effects; therefore it is worth trying more than one in any given cat.

 

Cyproheptadine: An oldie but goodie

Cyproheptadine has been around for decades and has been shown to result in weight gain in human pediatric patients. Given the complexity of the neurohormonal regulation of appetite, it is not a surprise that it remains a mystery how cyproheptadine or any of the other appetite stimulants truly influence appetite. Cyproheptadine is classified as an antihistamine but also has anti-serotonin effects via 5HT2 receptor subtype. It is metabolized by the liver and undergoes renal excretion, thus dose adjustment might be considered in patients with either renal or hepatic dysfunction. There are no clinically relevant retrospective studies or clinical trials documenting efficacy of cyproheptadine in cats, but an accepted dose range is 1 to 4 mg per cat every 12 to 24 hours. Side effects are generally minimal and are limited to hyperexcitability in some cats that is self-limiting.

 

Mirtazapine

Mirtazepine is a human antidepressant medication that has myriad effects on the central nervous system. It promotes norepinephrine and serotonin concentration via presynaptic receptor inhibition and 5HT1 agonism. Interestingly, it also has 5HT2 and 5HT3 antagonism, which is likely the mechanism for appetite stimulation. Previous doses for dogs and cats were extrapolated from human medicine. A dose of a quarter of a 15 mg tablet – or 3.75 mg – every three days was recommended for cats. Fortunately there is an increasing body of research into the pharmacokinetics and efficacy of mirtazapine in cats.

A placebo-controlled crossover study in 2011 demonstrated an increase in body weight in young healthy cats administered 1.88 mg per cat per day of mirtazapine. The dose range was 0.44 mg to 0.6 mg/kg. This same group of researchers also examined the clearance and half-life of mirtazapine in cats with chronic kidney disease (CKD) and with liver disease. They determined there is a prolonged half-life of the drug in these patients. Furthermore, they determined there is accumulation of the drug in CKD patients that are given the daily dose of 1.88 mg/cat. They did not examine drug clearance or accumulation in liver disease cats but suspected the results would be similar to the CKD group. Although no increased incidence of adverse events was noted in the daily treated CKD or liver disease group, they did propose that the prescribing clinician could consider a dosing schedule of every 48 hours in cats with CKD or liver disease.

The most common side effects include vocalization, behavior change, tremors and hypersalivation. These adverse effects were more commonly seen with the previously recommended dose of 3.75 mg per day, and seen far less often with the 1.88 mg per cat (or 0.44 mg/kg) per day. A retrospective study on mirtazapine toxicity in cats discussed that the serotonergic signs predominate in the toxic signs. Tremors, hypersalivation, hypertension, mydriasis, vomiting and vocalization are the more common signs seen with doses greater than 0.75 mg/kg. The ASPCA Animal Poison Control Center recommends treating these patients with cyproheptadine, which is commonly used to treat serotonin syndrome caused by other medications. It is important to note that previous studies have shown that higher doses of mirtazapine do not have a better effect on weight gain, thus the 1.88 mg per cat per day is the current recommended dose, or 0.44 mg/kg per day in very small or very large feline patients.

It is also notable that a transdermal preparation of miratazapine is the only FDA-approved medication for appetite stimulation in cats. Mirataz gel is a 2% preparation such that a 1.5-inch strip is equal to a 2 mg dose that can be placed on the ear pinna. Prospective evaluation of this drug has demonstrated favorable efficacy in healthy cats, geriatric cats and those with either liver or kidney disease.

 

Capromorelin

Ghrelin is a hormone secreted by the stomach that stimulates the portion of the hypothalamus associated with food intake. It also stimulates the pituitary gland to produce growth hormone. Drugs that act on the hypothalamic and pituitary ghrelin receptors are known as ghrelin receptor agonists. Capromorelin is one such drug. Entyce is an FDA-approved ghrelin receptor agonist for use as an appetite stimulant in dogs. Since ghrelin receptor agonists could influence growth hormone as well, laboratory animal studies have been conducted to determine if ghrelin receptor agonist drugs can improve healing time in surgical patients and improve body mass in cachexic patients. To date, there are not yet any clinical studies demonstrating these effects in our veterinary patients. The safety and efficacy trial to get Entyce approved was carried out in healthy beagle dogs with encouraging results. The current dose recommended for dogs is 3 mg/kg.

There is limited published data for capromorelin use in cats. In 2017, a safety and efficacy study was carried out on healthy research cats using capromorelin in doses of 6 mg/kg, 15 mg/kg, 30 mg/kg and 90 mg/kg per day. There was a statistically significant improvement in body weight in the capromorelin groups compared to controls. Adverse events were limited to hypersalivation, emesis, and lethargy or depression, which were more frequently seen with higher doses of the drug. Biochemical profile and necropsy findings were similar between control and treatment groups and were essentially unremarkable.

There is a growing concern over the clinical use of capromorelin in cats. The authors of the 2011 study of capromorelin in cats did note lethargy and depression, but cardiovascular parameters – such as heart rate and blood pressure – were not reported. In the ICU setting, we have observed some cats become profoundly bradycardic and hypotensive within one hour of being given capromorelin at a dose of 3 mg/kg. Most of these were self-limiting, but some were severe enough to require fluid resuscitation. There are anecdotes of similar adverse events occurring in cats at other specialty hospitals. It is likely there will be enough data for one or several institutions to publish data describing in more detail the incidence of adverse events in cats, and ideally identify at-risk populations. For now, it is wise to use caution if considering capromorelin administration in cats and to use it only if the cat has not responded to cyproheptadine or mirtazapine.  

 

CBD

It has long been known that marijuana gives people food cravings. Despite the difficulty in using marijuana for research purposes, there has been some forward movement in the use of marijuana in prescription pharmaceuticals. Marinol™ (dronabinol) is an FDA approved THC containing drug to treat anorexia in people with HIV, and nausea and vomiting in cancer patients being treated with chemotherapy. Marijuana contains THC and cannibidiols (CBD). Proponent of CBD products advertise that the CBD portion has therapeutic properties without giving the patient a high, thus is safer. The difficulty in recommending CBD products is that it is not regulated by the FDA thus there is no guarantee of purity, efficacy or safety of these products. Research using CBD is also challenging because the FDA still views the source, marijuana, as a federally banned substance. As veterinarians practicing in states (WA and OR) that have legalized recreational use of marijuana we have to accept that our clients have access not only to CBD products but also recreational marijuana and they may try to treat their pets ailments with these products. What should be emphasized is the lack of controlled clinical research into the efficacy and safety of CBD for various conditions. You can also educate the client regarding the lack of regulation of these products and that there could be potential for harm.

 

Other notable treatment tips

  • Appetite stimulant should not take the place of diagnostic testing.
  • Assisted feeding is the gold standard for nutritional intervention to best control nutrient profile and caloric intake in an ill feline.
  • Use of an appetite stimulant requires diligent monitoring of the quantity of food intake to adequately measure success of its use. Just because a cat is nibbling does not mean it is meeting its caloric requirement.
  • Although other medications, such as benzodiazepines, propofol (or other sedatives) and steroids can result in stimulation of appetite, they are not recommended as a prescribed appetite stimulant in cats.
  • Appetite stimulants are less likely to be efficacious in very ill cats, thus a more aggressive nutrition strategy would be recommended.
     

 

MEDICATION OVERVIEW

DRUG

DOSE

NOTES

Cyproheptadine

1 - 4 mg PO q 12 hours

 

Mirtazapine oral

1.88 mg per cat or 0.44 mg/kg PO q 24 hours

Consider q 48 hr dosing in cats with CKD or liver disease

Mirtazapine transdermal

1.5-inch strip equivalent to 2 mg on inner ear pinna q 24 hours

Consider q 48 hr dosing in cats with CKD or liver disease

Capromorelin

Use with caution if other medications are ineffective.
0.3 mg/kg PO q 24 hours.

Monitor for hypotension and bradycardia

 

 

References

Poole M, Quimby JM, Hu T, et al. A double-blind, placebo-controlled, randomized study to evaluate the weight gain drug, mirtazapine transdermal ointment, in cats with unintended weight loss. J Vet Pharmacol Ther. 2019 Mar;42(2):179-188.

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 Sep-Oct;25(5):985-9.

Quimby JM, et al. Studies on the pharmacokinetics and pharmacodynamics of mirtazapine in healthy young cats. J Vet Pharmacol Ther. 2011 Aug;34(4):388-96.

Quimby JM, Gustafson DL, Samber BJ, 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 Sep;197(3):651-5.

Quimby JM, et al. Assessment of transdermal (lipoderm) mirtazapine as an appetite stimulant in cats with chronic kidney disease. J Vet Intern Med. 2017;31:1594.

Wofford JA, Zollers B, Rhodes L, et al. Evaluation of the safety of daily administration of capromorelin in cats. J Vet Pharmacol Ther. 2018 Apr;41(2):324-333.

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