Donald Tummons, D.V.M.

An 11 year-old male cat showed aggressive behavior towards other cats and also started urinary spraying. Buspirone 2.5mg/ml flavored suspension was tried. It was extremely difficult for the owner to give the oral suspension and after a few days the cat was vomiting the medication.

The owner was instructed to apply 0.1ml of transdermal buspirone 2.5mg/0.1ml pluronic lecithin organogel (PLO) topically inside the tip of the ear twice a day.

After the first dose, the owner noticed the medication made the cat too sleepy and the dose was decreased to 0.05ml (1.25mg of buspirone). The cat's aggressive behavior has been controlled on the lower dose with a few exceptions and the owner then increased the dose to 2.5mg of buspirone for a couple of doses. The owner is amazed how easy it is to apply the medication.
Amitriptyline hydrochloride is one of the most widely used tricyclic antidepressants (TCAs) in companion animal behavioral medicine, exerting antihistaminic, anti-inflammatory, analgesic, and antidepressant effects. Amitriptyline increases synaptic activity of serotonin and norepinephrine, has significant central and peripheral anticholinergic activity, and stimulates beta-adrenergic receptors in smooth muscle (e.g. the bladder), causing a decrease in smooth muscle excitability and a subsequent increase in bladder capacity and storage.

Although amitriptyline has been used successfully to treat behavior-related and urinary tract disorders in cats and dogs, the drug is not approved by the FDA for veterinary use and therefore is not available as a veterinary preparation.

Compendium 23(5) May 2001: 433-7
In animals, tricyclic antidepressants have actions similar to those of phenothiazines in altering avoidance behaviors. Imipramine has been used for the following indications:
  • Cats: urethral incompetence
  • Dogs: treatment of separation anxiety and other behaviors, cataplexy, urethral incompetence
  • Horses: narcolepsy and ejaculatory dysfunction
"Naltrexone may be useful in the treatment of self-mutilating or tail-chasing behaviors in dogs or cats... [A synthetic opiate antagonist,] naltrexone is generally considered to be contraindicated in patients physically dependent on opiate drugs, in hepatic failure or with acute hepatitis."

Doses for Dogs:

As adjunctive therapy in behavior disorders:

For tail chasing or excessive licking: First give 0.01mg/kg SubQ of naloxone to determine if narcotic antagonists may be effective. If so, give naltrexone PO at 1 - 2 mg/kg daily. Long-term therapy may be required. (Crowill-Davis 1992)

For the adjunctive treatment of acral pruritic dermatitis:
2.2mg/kg PO once daily for one month trial. Some dogs exhibit drowsiness and minor changes in behavior. 50-60% of patients have benefited... (Rosychuck 1991)
involves excessive licking of the paws or flank, even to the point of self-mutilation, and can produce ulcerations and infections that require medical treatment. Based on patterns of behavior and response to medication, veterinary scientists propose that canine acral lick dermatitis, also known as canine compulsive disorder (CCD), is an animal model of human obsessive-compulsive disorder. A randomized, placebo-controlled, double-blind crossover clinical study evaluated the efficacy of the medication clomipramine for treatment of CCD. Fifty one dogs with CCD were given clomipramine 3 mg/kg [1.3 mg/lb] of body weight orally every 12 hours for 4 weeks and then placebo for 4 weeks. While drug therapy can be helpful, therapy may need to include behavior modification to optimally manage CCD.

J Am Vet Med Assoc 1998 Dec 15;213(12):1760-6 Efficacy of clomipramine in the treatment of canine compulsive disorder. Click here to access the PubMed abstract of this article.

Arch Gen Psychiatry 1992 Jul;49(7):517-21 Drug treatment of canine acral lick. An animal model of obsessive-compulsive disorder. Click here to access the PubMed abstract of this article.
Evidence suggests that social dominance aggression may be modulated by serotonergic mechanisms. Fluoxetine (Prozac�), a specific inhibitor of serotonin reuptake, is a popular human antidepressant which has been used successfully to decrease social aggression in dogs and monkeys.

J Am Vet Med Assoc 1996;209:1585-1587 Use of fluoxetine to treat dominance aggression in dogs. Click here to access the PubMed abstract of this article.
Administration of fluoxetine hydrochloride for treatment of urine spraying in cats can be expected to considerably reduce the rate of urine marking. Pryor et al. recommend that most cats should be treated more than eight weeks before treatment is withdrawn. Cats that vertically marked a mean of > or = 3 times per week were treated for 8 weeks with fluoxetine (1mg/kg PO daily- dosage individualized for each cat by a compounding pharmacy) or fish-flavored liquid placebo. When treatment was discontinued after 8 weeks, the spraying rate of cats that had received treatment varied. The main adverse reaction to the drug was a reduction in food intake, which was observed in 4 of 9 treated cats.

J Am Vet Med Assoc 2001 Dec 1;219(11):1557-61 Effects of a selective serotonin reuptake inhibitor on urine spraying behavior in cats. Click here to access the PubMed abstract of this article.
In a multi-cat household, it is important to determine which cat is inappropriately eliminating so that the proper intervention can be made. Even if one cat is observed marking or urinating outside the box, it does not rule out the possibility that other cats are also behaving inappropriately. When it is necessary to identify which cat in a multi-cat household is spraying or inappropriately eliminating, fluorescein can be orally administered once daily in the evening with food for three days. That cat's urine will fluoresce under ultraviolet light for approximately 24 hours. To detect urine containing the fluorescein indicator, the client needs to scan the household with a commercial black light or black light purchased from a novelty store. Although urine will commonly glow, fluorescein treated urine fluoresces a characteristic bright yellow. Caution clients that they may reveal previously undiscovered sites of elimination; advise them not to become alarmed or angry. By administering the dye to different cats at two day intervals, the culprit can be identified.

Pharmacological support for urine spraying or marking is usually needed only for cases with underlying anxiety or problems with social interactions between cats (clomipramine), or for cats with interstitial cystitis (amitriptyline, doxepin). Administration of fluoxetine hydrochloride for treatment of urine spraying in cats may also considerably reduce the rate of urine marking.
A 10-year-old castrated male domestic cat was admitted to the hospital at the School of Veterinary Medicine, Tufts University. A diagnosis of territorial urine marking was made. Treatment included behavior modification and the administration of cyproheptadine, which resulted in the immediate arrest of undesirable urine marking. Cyproheptadine administration was adjusted to determine the lowest dosage that effectively maintained the cat's consistent use of the litter box. It was recommended to continue cyproheptadine administration for at least 1 year before any attempt to withdraw its use. Another study recommended a dose of 2 mg, p.o., every 12 hours. This antihistamine, also prescribed for its appetite stimulant effects in cats, has antiandrogenic effects in other species.

J Am Vet Med Assoc 1999 Aug 15;215(4):501-2, 482 Use of cyproheptadine to control urine spraying in a castrated male domestic cat. Click here to access the PubMed abstract of this article.

J Am Vet Med Assoc 1999 Feb 1;214(3):369-71, 351-2 Use of cyproheptadine to control urine spraying and masturbation in a cat. Click here to access the PubMed abstract of this article.

Cyproheptadine hydrochloride was administered to 20 presumed or proven allergic cats to determine its efficacy in controlling pruritus. Each cat received 2 mg, orally, every 12 hours. The pruritus was satisfactorily controlled in 9 cats. Side effects were seen in 8 cats, and included polyphagia, sedation, vocalization, affectionate behavior, and vomiting.

Can Vet J 1998 Oct;39(10):634-7 Observations on the use of cyproheptadine hydrochloride as an antipruritic agent in allergic cats. Click here to access the PubMed abstract of this article.
A study of 11 cats assessed the clinical response to a treatment regimen that included clomipramine and behavior modification in cats diagnosed with anxiety-related or obsessive-compulsive disorders. Presenting signs were urine spraying in seven cases, overgrooming in three and excessive vocalization in one. Clomipramine was administered orally once daily, with a mean starting dose of 0.4 mg/kg. If necessary, the dose was adjusted according to the clinical response of each cat. The average maintenance dosage was 0.3 mg/kg once daily. The researchers concluded that clomipramine was effective in controlling the signs of anxiety-related and obsessive-compulsive disorders in 10 of 10 assessable cases when used in combination with behavior modification, and the drug was well tolerated.

Aust Vet J 1998 May;76(5):317-21 Use of clomipramine in the treatment of anxiety-related and obsessive-compulsive disorders in cats. Click here to access the PubMed abstract of this article.
Selegiline is a monoamine oxidase (MAO) inhibitor indicated for use in dogs to control signs associated with canine cognitive dysfunction syndrome and uncomplicated pituitary-dependent hyperadrenocorticism (PDH). Studies suggest that selegiline may enhance survival rates. The recommended dose for cognitive dysfunction is 0.5 to 1 mg/kg, and for PDH is 1 mg/kg, orally each morning. If no improvement is seen after 2 months, the dose can be increased to the maximum of 2mg/kg/day. If there is no clinical improvement after 1 month at 2mg/kg/day, alternative therapy or further evaluation should be considered. "Overall, selegiline is well tolerated... Gastrointestinal disturbances, particularly vomiting and diarrhea, are the most common side effects reported. Diarrhea may resolve when the drug is discontinued or the dose decreased. Other adverse effects include hyperactivity, agitation, restlessness, and insomnia. A dose reduction or discontinuation of therapy also resolves these problems."

Compendium March 2000; 22(3):204-5