Disorders of appetite are very common in animals. Anorexia is a common clinical problem seen with many systemic diseases, and it exacerbates disease-induced catabolism. In the anorectic animal that does not respond to coaxing with small amounts of highly palatable foods, drug therapy may be used to stimulate appetite. If such therapy is unsuccessful, more invasive procedures, such as nasogastric or gastrotomy tube feeding, or total parenteral nutrition may be necessary to provide sufficient nutrition.

Obesity as a result of overeating is common in companion animals and is best managed by educating the owner and regulating the animal's diet. If weight management is unsuccessful, pharmacologic therapy can be considered. Dirlotapide is a microsomal triglyceride transfer protein (MTP) inhibitor developed specifically for weight loss in dogs. MTP catalyzes the assembly of triglyceride-rich apolipoprotein B-containing lipoproteins to form chylomicrons in the intestinal mucosa and very low-density lipoproteins in the liver. Following oral administration, dirlotapide has in vivo selectivity for intestinal MTP. The mechanism of weight loss action is not completely understood, but dirlotapide appears to reduce fat absorption and send a satiety signal from lipid-filled enterocytes. Dirlotapide also decreases appetite in a dose-dependent manner, probably via increased release of peptide YY into the circulation. The decrease in food intake is responsible for most of the weight reduction effect.

Dirlotapide is available systemically, but absorption in dogs is highly variable. Absorbed dirlotapide is metabolized in the liver; parent drug and metabolites are secreted in the bile, with potential for enterohepatic circulation. Although blood concentrations do not directly correlate with effectiveness (effectiveness has been linked to drug concentrations in the gut), they seem to correlate with systemic toxicity.

Dirlotapide is available as a 5 mg/mL solution for oral administration. The dose is adjusted according to the weight loss of each individual dog. The initial dosage of 0.5 mg/kg is doubled after 14 days and then adjusted monthly; the maximum permitted daily dosage is 1.0 mg/kg, although dosages as high as 10 mg/kg have been administered to dogs without severe adverse effects in safety studies. Dirlotapide can be used without changing the dog's current feeding or exercise regimens, but food intake should be monitored during weight stabilization to establish feeding and exercise routines that will minimize post-treatment weight gain. Anorexia, emesis, and loose stools occur in some dogs. The incidence of emesis generally increases with dose and decreases with treatment time. Elevations in hepatic trans-aminase activity were seen in dogs treated with >1.5 mg/kg/day, but were not associated with clinical signs or histopathologic evidence of hepatic degeneration or necrosis.

Dirlotapide should not be used in cats. It increases the risk of hepatic lipidosis during weight loss in obese cats. Dirlotapide is not recommended for use in dogs currently receiving longterm glucocorticoid therapy or dogs with liver disease. Adverse reactions associated with humans ingesting dirlotapide include abdominal distention, abdominal pain, diarrhea, flatulence, headache, increased serum transaminases, nausea, and vomiting.

Drugs used as appetite stimulants in monogastrics include B vitamins, glucocorticoids, anabolic steroids, benzodiazepines, and cyproheptadine (see Systemic Pharmacotherapeutics of the Digestive System: Drugs Used to Stimulate Appetite).

Table 1
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Drugs Used to Stimulate Appetite Drug Dosage Prednisone 1 mg/kg, PO, every other day Diazepam Cats: 0.005–0.4 mg/kg, IM or IV, sid; 1 mg/kg, PO, sid Oxazepam Cats: 2 mg, PO, bid Cyproheptadine Cats: 1–4 mg, PO, bid Mirtazapine Cats: 3.75 mg/cat (¼ of a 15 mg tablet), PO, every 3 days Dogs: ¼ of a 15 mg tablet for dogs <7 kg, ½ of 15 mg tablet for dog, 8–15 kg, 15 mg for dogs 16–30 kg, 30 mg for dogs >30 kg; no higher than 30 mg per dog. Megestrol acetate Dogs: 5 mg/kg, PO, sid

B vitamin preparations have been administered PO and parenterally to debilitated animals, especially horses, to promote appetite.

Glucocorticoids increase gluconeogenesis and antagonize insulin for an overall hyperglycemic effect. Appetite is stimulated by the steroid-induced euphoria. Continued use of glucocorticoids has catabolic effects because skeletal muscle and collagen proteins are broken down to provide the precursors for gluconeogenesis.

The benzodiazepines are effective appetite stimulants in cats (but not dogs) by effects induced by γ-aminobutyric acid (GABA) and by central inhibition of the satiety center in the hypothalamus. Diazepam can be administered IV, IM, or PO, sid. Cats that respond begin eating within a few seconds of IV administration, so palatable food should be promptly available. Oxazepam, a metabolite of diazepam, can be given PO. Diazepam is the more effective appetite stimulant but also has a greater sedative effect than oxazepam.

Cyproheptadine is an antihistamine with antiserotonin action. It promotes appetite by inhibition at the serotoninergic receptors, which control satiety. It is used in cats as an appetite stimulant. CNS excitement and aggressive behavior may be seen in some cats.

Mirtazapine is a noradrenergic and specific serotonergic antidepressant. It is a potent antagonist of 5-HT₂ and 5-HT₃ receptors, but has no significant affinity for the 5-HT_1A and 5-HT_1B receptors. Mirtazapine is a potent antagonist of histamine (H₁) receptors, which explains its prominent sedative effects. It usually does not cause anticholinergic effects, serotonin-related side effects, or adrenergic side effects (orthostatic hypotension and sexual dysfunction). Antihistaminic side effects of drowsiness and weight gain are prominent. Mirtazapine is used for disorders in which inappetence and nausea go together, such as intestinal and gastric disease, liver or kidney disease, or any other condition involving both nausea and appetite loss. Mirtazapine can also be used to treat the nausea and appetite loss caused by chemotherapy.

In dogs, mirtazapine is typically given once a day, while cats are given mirtazapine twice a week. It should be used with caution in dogs and cats with severe liver or kidney disease, as mirtazapine clearance will be reduced. In cats and small dogs, it is difficult to reduce the dose as the smallest tablet manufactured cannot be accurately cut much smaller than the regular dosing schedule allows.

Megestrol acetate is a synthetic progestin. It has significant antiestrogen and glucocorticoid activity, with resulting adrenal suppression. It is used to stimulate appetite and promote weight gain in people with cancer and cachexia (related to acquired immunodeficiency syndrome) and may have a similar effect in anorectic cats and dogs. Megestrol acetate is contraindicated in pregnant animals and in animals with uterine disease, diabetes mellitus, or mammary neoplasia. In cats, megestrol acetate can induce a profound adrenocortical suppression, adrenal atrophy, and diabetes mellitus, which may or may not be reversible.

Last full review/revision March 2012 by Patricia M. Dowling, DVM,MSc, DACVIM, DACVCP; Johann (Hans) Coetzee, BVSc, CertCHP, PhD, DACVCP