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Compendium August 2006 (Vol 28, No 8)

Understanding Behavior: "Selecting Psychoactive Medications for Behavior Problems"

by Sharon L. Crowell-Davis, DVM, PhD, DACVB

    Although many behavior problems can be adequately addressed by environmental management and behavior modification alone, some cases require treatment with psychoactive medication. Even patients in which psychoactive medication is not an essential part of the treatment typically improve faster if appropriate medication is used, which many owner's find appealing.

    To date, only two medications for behavior problems have FDA approval for use in animals: selegiline (Anipryl, Pfizer Animal Health) for canine cognitive dysfunction, and clomipramine (Clomicalm, Novartis Animal Health) for the treatment of separation anxiety in dogs (if used in combination with behavior modification). Other use of either of these drugs or other psychoactive drugs is extralabel. Under the Animal Medicinal Drug Use Clarification Act of 1994, extralabel use of drugs on animals requires a valid veterinarian-client-patient relationship and that the veterinarian make the diagnosis and has a valid reason for selecting a particular drug. If a trainer or "behaviorist" who is not a veterinarian makes a diagnosis and recommends a drug, the veterinarian-client-patient relationship does not apply. Veterinarians who prescribe a drug based on such a recommendation without completing their own evaluation of the patient could be guilty of malpractice. It is essential that veterinarians perform a complete physical and behavioral evaluation before prescribing psychoactive medication.

    A review of all psychoactive medications that can be used in veterinary patients is beyond the scope of this column; only the most common categories and drugs are ­discussed. For further information, see Crowell-Davis and Murrays' Veterinary ­Psychopharmacology.1

    Several major activities of various psychoactive medications are the basis for their use in treating behavior problems in pets. Many medications have anxiolytic properties, which are very useful because fear and anxiety are most commonly at the root of behavior problems in pets. Some medications have anticompulsive activity and can be useful in treating various compulsive disorders in which a patient spends large amounts of time engaging in repetitive behaviors independent of its current environment. Certain medications also decrease aggressiveness by increasing the threshold of external stimuli required to trigger aggression and/or by decreasing the intensity of aggressiveness when it does occur. Drugs that help with aggression should be considered to be more like a rheostat than an "off" switch in that they can decrease the probability that aggression will occur, but no drug is guaranteed to stop aggression in a conscious animal. Management and behavior modification are always critical in treating animals that may injure humans or other animals. For geriatric pets with cognitive decline analogous to Alzheimer's disease in humans, selegiline can partially reverse the clinical signs and slow progression of the disease, although it cannot cure it.

    Drugs with anxiolytic properties include benzodiazepines, selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, and azaperones. Benzodiazepines have the advantage of a rapid onset of action and can be very useful in severely anxious patients if the owners want rapid improvement. Some of the more common benzodiazepines are listed in Table 1 . Adverse effects include sedation, ataxia, muscle relaxation, paradoxical excitation, and increased appetite. Alprazolam has a rapid onset of action and good antipanic effect and has been beneficial in treating storm phobia.2 Laboratory studies3 have shown clonazepam to be less toxic to cats than is chlordiazepoxide, diazepam, or flurazepam. Clorazepate is the most expensive benzodiazepine listed but generally has a longer duration of clinical efficacy. Diazepam is probably the most common benzodiazepine in veterinary medicine but is occasionally hepatotoxic in cats. Oxazepam has no active metabolites and is therefore probably one of the safer benzodiazepines to use in geriatric patients and patients with liver disease.

    SSRIs, tricyclic antidepressants, and azaperones all have anxiolytic properties. Some of the more common drugs are listed in Table 2 . Amitriptyline is not listed because although it became popular when it was the least expensive drug with serotonin reuptake inhibition properties, it usually has significant adverse effects and has since been matched in cost by drugs with a better efficacy:adverse effect ratio. SSRIs and tricyclic anti­depressants can also be beneficial in treating aggression and compulsive disorder. They should not be given concurrently with a monoamine oxidase inhibitor because significant adverse drug interactions may occur.

    Buspirone

    Buspirone is the only commercially available azaperone. It is a serotonin 1A agonist that is used to treat generalized anxiety disorder in humans. Historically, it has primarily been used in cats to treat urine spraying.4 Although buspirone was once cost prohibitive for the average dog owner, its price has decreased substantially in the past few months, making it a more viable option for dogs with various anxiety problems. One of the great advantages of buspirone is that adverse effects are uncommon, although paradoxical anxiety has occasionally been observed in patients. When receiving bu­spirone, timid cats often exhibit behavioral changes that may be generally described as indicative of increased self-confidence.

    Selective Serotonin Reuptake Inhibitors

    With prolonged use of SSRIs, the serotonin receptors down-regulate. Common behavioral effects include decreased reactivity, aggression, fear, and compulsive behaviors. Of several commercially available SSRIs, fluoxetine is currently the least expensive. Cost is important to many owners because pets with behavior problems are likely to need medication for several months. Adverse effects are uncommon with the use of SSRIs. The most commonly reported adverse effects are mild sedation, decreased appetite, and changes in gastrointestinal function, such as constipation or diarrhea. Sedation and decreased appetite usually last only 1 to 2 weeks. SSRIs may alter blood glucose levels. Therefore, although they can be given to diabetic patients, monitoring of glucose levels should initially be increased until the individual patient's response to the SSRI is identified.

    Tricyclic Antidepressants

    Tricyclic antidepressants inhibit the reuptake of both serotonin and norepinephrine, eventually resulting in down-regulation of the serotonin and norepinephrine receptors. The effect of tricyclic antidepressants on serotonin and norepinephrine results in desired behavior changes, including decreased reactivity, aggression, and fear. Clomipra­mine--the most serotonin-specific of the tricyclic antidepressants--also has good anticompulsive effects. Tricyclic antidepressants also have antihistaminic and anticholinergic effects and are a1-adrenergic antagonists, all of which can cause adverse effects that vary substantially among tricyclic antidepressants because of ­differing intensities of the five major effects. Although the adverse effects of tricyclic antidepressants are uncommon, they are generally more common than the adverse effects of SSRIs. The most common adverse effects include sedation; gastrointestinal changes, including vomiting, constipation, and diarrhea; urinary retention; changes in appetite; and ataxia. Although the total daily dose can be given once for the behavioral effect, dividing the total dose into two smaller doses and giving the medication with food decreases the occurrence of vomiting. Clomipramine is available as a beef-flavored chewable tablet (Clomicalm), which is FDA approved in the treatment of separation anxiety in dogs. Clomipramine is also useful for a variety of other behavior disorders, including storm phobia, urine spraying in cats, and compulsive disorder. Imipra­mine, which is used to treat nocturnal enuresis (bed wetting) in children, may be particularly useful in treating submissive urination and excitement urination in dogs.

    Selegiline

    Selegiline, a monoamine oxidase B inhibitor, can be useful in treating both cats and dogs with cognitive decline. Both species should be administered 0.5 to 1 mg/kg PO sid. Selegiline should not be given with SSRIs, tricyclic antidepressants, or aza­perones, but it can be given with benzodiazepines. At a dose of 1 mg/kg/day, selegiline also prolongs the life of otherwise healthy elderly dogs.5

    Acepromazine

    Acepromazine is an antipsychotic with sedative properties. It does not have true anxiolytic effects and is therefore not generally appropriate in treating anxiety disorders, including storm phobia and separation anxiety. The only appropriate use of acepromazine in these cases is in combination with a true anxiolytic in patients that engage in behaviors that may be harmful to themselves (e.g., jumping through windows).

    Conclusion

    When choosing a drug for anxiety, aggression, or compulsive disorder, it is important to remember that each patient is unique. Unfortunately, to date, there is not a simple test or even a specific set of clinical signs to determine which drug is best. Therefore, the only option for a given patient is trial-and-error testing. An initial treatment should be selected based on the patient's behavior problem and medical conditions, the side effects and safety profile of the drug, other medications that the patient is already receiving, and the client's budget. Unless the patient exhibits adverse effects, that treatment should be tried for at least 1 week for benzodiazepines or 1 month for the other drugs discussed. If after 1 month there are no adverse effects but the patient has improved insufficiently, the dose can be increased. If the maximum dose is reached or if adverse effects occur at levels lower than the maximum dose and the problem is still not adequately resolved, another drug should be tried. The fact that a patient does not respond as desired to one drug does not mean there will not be a beneficial effect from another drug, even one in the same ­family.

    The use of medication by itself is not a permanent cure of behavior problems. Even in patients that respond very well to medication, the ultimate goal is to wean the patient from medication. Environmental management and appropriate behavior modification should always be used in conjunction with medication. Once the patient's behavior has improved to the point that the veterinarian and owner agree that the problem is sufficiently resolved, the pet should be administered medication for another 2 to 3 months and then gradually weaned from it. Weaning can be done rapidly (i.e., decrease the dose by approximately 25% every week) in pets with minor problems that have responded rapidly to treatment. Pets that began treatment with major problems and/or took a long time to improve may need to be weaned over a period of months.

    1. Crowell-Davis SL, Murray T: Veterinary Psychopharmacology. Ames, IA, Blackwell Publishing Professional, 2006.

    2. Crowell-Davis SL, Seibert LM, Sung W, et al: Use of clomipramine, alprazolam and behavior modification for treatment of storm phobia in dogs. JAVMA 226:744-748, 2003.

    3. Randall LO, Kappell B: Pharmacological activity of some benzodiazepines and their metabolites, in Garattini S, Mussini E, Randall LO (eds): The Benzodiazepines. New York, Raven Press, 1973, pp 27-51.

    4. Hart BL, Eckstein RA, Powell KL, Dodman NH: Effectiveness of buspirone on urine spraying and inappropriate urination in cats. JAVMA 203(2):254-258, 1993.

    5. Ruehl WW, Hart BL: Canine cognitive dysfunction, in Dodman NH, Shuster L (eds): Psychopharmacology of Animal Behavior Disorders. Malden, MA, Blackwell Science, 1998, pp 283-303.

    References »

    NEXT: Abstract Thoughts (August 2006)

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