Drugs Used for Appetite Stimulation in Dogs & Cats

Mirtazapine is a 5-HT_2A-, 5-HT_2C-, 5-HT₃-, and H₁-receptor antagonist and a presynaptic alpha-2−autoreceptor antagonist that causes enhanced noradrenergic and serotonergic transmission. Effects on appetite may be related to antagonism of 5-HT_2C and H₁ receptors involved in appetite regulation; alpha-1 receptor affinity is much lower than alpha-2 receptor affinity. An antiemetic effect may also be mediated by antagonism of the 5-HT₃ receptor.^3-5

Dosage (Cats, Dogs)

• Cats
  • 0.5 mg/kg PO every 24 hours (practically, ≈1.88-3.75 mg/cat PO every 24 hours, with the larger dosage being for larger cats)⁶ 
    • Frequency should be decreased to every 48 hours in geriatric cats or those with kidney disease (International Renal Interest Society stage II-IV).⁴ 
    • Frequency should be decreased to every 48 to 72 hours in cats with liver disease (less frequently in patients with more severe disease).⁷
  • 1.5-inch strip (2 mg/cat) of the FDA-approved transdermal product on pinna every 24 hours⁸ 
    • Onset of activity may be slower than with oral administration.⁹
  • Compounded transdermal products are also available, but composition, absorption, and stability vary. These products may therefore produce substantially lower drug concentrations than intended. 
    • Two commercially available compounded products had 44% to 87% and 55% to 75% of the label concentration of mirtazapine, respectively.¹⁰ 
• Dogs: 0.6 mg/kg PO every 12 hours¹¹
  • Half-life is shorter in dogs than in cats. 

Key Points (Cats)

• In young, healthy cats, a median dose of 0.5 mg/kg PO significantly increased food consumption; increased effect was not seen when the dose was increased to 0.9 mg/kg.⁶
• In cats with chronic kidney disease, 1.88 mg/cat PO every 48 hours increased appetite, body weight (median weight gain, 0.4 lb [0.18 kg] over 3 weeks), and activity level and reduced vomiting compared with placebo.¹² 
• In cats with clinically significant weight loss and a variety of conditions (not including severe kidney disease or neoplasia) treated with the transdermal product at 2 mg/cat every 24 hours, average weight gain was 3.9% after 2 weeks.⁸
• Dual antiemetic and appetite stimulant effects may be useful in patients undergoing chemotherapy.
  • Evaluation is currently limited to an uncontrolled study in cats with lymphoma.¹³
• Adverse effects of oral administration can include vocalization, hyperactivity/agitation, vomiting, ataxia, tremors, hypersalivation, mydriasis, tachypnea/tachycardia, and lethargy.¹⁴
  • Adverse effects are more likely in cats given >2.5 mg/kg every 24 hours and are uncommon in cats given <0.75 mg/kg every 24 hours. 
  • Subclinical ALT elevation that resolved after discontinuation of the drug was reported in one cat.¹²
• Transdermal formulations may cause erythema, flaking, crusting, or pruritus at the application site, but these effects typically resolve with discontinuation of the drug.^8,13
• Serotonin syndrome can occur in elderly humans administered high doses and when mirtazapine is administered in conjunction with other serotonergic drugs, including selective serotonin reuptake inhibitors (eg, fluoxetine), monoamine oxidase inhibitors (eg, selegiline), and tricyclic antidepressants (eg, amitriptyline).¹⁵ Use with tramadol in veterinary patients is also theoretically contraindicated because tramadol inhibits serotonin reuptake.¹⁶ Although there is no documentation of serotonin syndrome in companion animals given clinically relevant dosages, these combinations should be avoided if possible, and close monitoring for adverse effects is recommended.    

Key Points (Dogs)

• Efficacy data in dogs are primarily anecdotal, except for a noncontrolled case series.¹⁷
• May be used anecdotally in combination with capromorelin or as an alternative, particularly in dogs that do not tolerate liquids or have excessive salivation when given capromorelin  
• Adverse effects are possible.
• In research beagles, no adverse effects were seen with chronic administration of 2.5 or 15 mg/kg every 24 hours for 1 year.¹⁸ Mild ALT and ALP elevation, mild anemia, and weight loss were seen within 6 months with administration of 80 mg/kg every 24 hours.