SHARON CROWELL-DAVIS
25.1 Why Use Medications?
All of the emotions are a consequence of chemical reactions within the central nervous system (CNS). Ideally, an animal’s genetics, diet, experience, and environment are such that the various neurochemicals that affect emotion are in the appropriate amount and location for the animal to primarily experience positive affect, and only experience negative affect when there is a strong reason to, such as a cat being attacked by a dog. In this situation, the emotion of fear, the well-known ‘fight-or-flight’ response, will occur. If it is able to, the cat will likely run away, climb a tree, or hide in a location where the dog cannot reach it. If it cannot escape, it will begin using its teeth and claws to defend itself. In this case fear is normal, and facilitates actions that maximize the likelihood of survival.
If the cat experiences the same fear upon seeing an unknown dog through a window, or encountering an unfamiliar human who is visiting the home and represents no threat of harm to the cat, its well-being may be adversely affected. Returning to a normal state of mental health, i.e., the cat does not experience fear when there is no danger, requires a change in the chemical reactions in the animal’s brain. In many cases, this can be achieved satisfactorily without using pharmacologic treatments, as is discussed in Chapter 24, this volume. However, in severe cases, or to make recovery occur faster, pharmacologic medications are often needed.
While for various reasons many individuals oppose the use of medication, if we are focusing on optimizing the patient’s welfare we must consider the potential benefits of pharmacologic agents, especially anxiolytic medications in animals that have developed disorders of anxiety or fear. Important considerations include the type of problem, severity of the problem, medical problems the animal has (e.g., diabetes), the owner’s ability to medicate the patient, existing evidence of potential benefits, and potential adverse side-effects. In many cases, the use of appropriate medication increases – often dramatically – the patient’s welfare. Sometimes medications are used in good part because the patient’s behavior is disturbing to the owner. For example, a storm phobic dog may howl and destroy things in the house. In contrast, many storm phobic cats simply hide. Is the welfare of the cat that is hiding any less compromised than that of the dog that is showing signs of distress? Probably not. The author has one cat with storm phobia. In the case of mild storms, we simply ensure that she has a good place to hide. With a mild storm and the availability of a good hiding spot, such as under a particular desk, her body language does not show substantial fear; however, signs will become evident if she is taken out of her hiding place. In the case of severe storms, or if her body language shows that she is fearful even while hiding, she is given an anxiolytic, not for the convenience of the author, but for the welfare of the cat.
It is beyond the scope of this single chapter to cover all indications, contraindications, dosing protocols, costs, and other issues for all medications that may benefit a patient’s psychological well-being. For a more comprehensive resource, see Veterinary Psychopharmacology, 2nd edition (Crowell-Davis et al., 2019b).
25.2 Decisions to Use Medication: Legal, Ethical, and Cost Issues
Prescription medications intended for animals must be prescribed by a veterinarian. The veterinarian must make the decision to recommend medication based on their own medical and behavioral examination and their own diagnostic assessment. Additional information that may be used in making a diagnosis includes reports of the patient’s behavior and mental status from the pet owner, trainers who have worked with the animal, animal behaviorists who are not veterinarians who have directly observed the animal, and others who have directly observed the animal. The prescribing veterinarian must perform their own direct examination of the patient, as it is both illegal and unethical for a veterinarian to provide a prescription based solely on the recommendation of another individual, even if they are a highly experienced animal behaviorist.
Not all of the psychoactive medications available on the market are in regular use in veterinary medicine or, most importantly, have evidence-based documentation of their efficacy and side-effect profile. Therefore, in the sections covering specific medications, only the more commonly used medications which currently have evidence-based documentation of their effects on at least one species of common veterinary patients are included.
25.2.1 The Animal Medicinal Drug Use Clarification Act (AMDUCA)
In the United States, the use of most psychoactive medications in animals is extra-label, i.e., the medication is not approved by the U.S. Food and Drug Administration (FDA) for the species and problem being treated. There are only a few exceptions at this time, i.e., Clomicalm (clomipramine) for separation anxiety in dogs, Anipryl (l-deprenyl) for cognitive dysfunction in elderly dogs, Sileo (dexmedetomidine) for noise aversion in dogs, and Reconcile (fluoxetine) for separation anxiety in dogs. All other uses of these medications are extra-label, for example, fluoxetine use in cats to treat separation anxiety and clomipramine use in dogs to treat storm phobia.
In all cases of extra-label use, the client should be informed of the extra-label status of the medication. It is advisable to accompany verbal explanations with a printed information sheet that discusses the extra-label use of medications, the reasons for this medication being used, the potential benefits, and the potential adverse effects. Have two copies, one of which the client signs, indicating that they have been given the information and understand it; this copy goes in the patient’s record. The other copy is for the client to take home to reread at their leisure.
25.2.2 Cost
Owners are usually paying for their pet’s medication out of their own pocket. As a consequence, it is important to follow changes in price of the various psychoactive medications that are useful for pets. Substantial price changes can occur, sometimes very quickly. Therefore, current price of a medication, in addition to potential benefits and side-effects, should be taken into consideration when making a decision on which medication to prescribe.
25.2.3 Medicating the patient
Many psychoactive medications are given daily, or at least frequently. Getting patients to take medications on such a regular basis can be challenging. In some cases, the manufacturer has placed the active ingredient in a chewable form that the patient finds at least acceptably palatable. For dogs and cats, hiding the pill in one of the various snack ‘pockets’ that are available over the counter will facilitate voluntary consumption.
Usually, dogs are the easiest, as many dogs will gulp food, and can be relied on to do so if there is a routine that facilitates gulping. For example, begin by giving the dog a highly palatable treat at a particular time of day. The treat should be of the sort that can be used to hide medication, such as a meatball, piece of hot dog, or pocket. If the dog needs the treat to be tossed in order to gulp it without tasting, begin with gentle tosses at a short distance. Then proceed to tossing at a greater distance and with the style that is most likely to result in the dog gulping without chewing or otherwise pausing to taste. Once this is accomplished, hide the medication inside the treat, and medicate the dog this way.
Cats can be more difficult, as they do not often gulp without tasting the way dogs do. Nevertheless, a highly palatable food can be an excellent motivator for cats. One can train a cat to accept being given a pill or a liquid medication. In a similar fashion to training dogs, begin by taking the cat to a specific location, at about the same time of day, and giving it a highly palatable treat. This does not have to be something labeled as a ‘treat’ in the commercial cat food market. It can be a teaspoon of a wet food that the cat is particularly fond of, a bit of fish, or anything else that the cat really likes, does not routinely get, and is safe to eat. After that habit is established, if the cat has to be given a pill it is not going to voluntarily consume, the owner starts the training by briefly placing their hands over the head and jaw of the cat the same way they would if they were going to open the cat’s mouth to pill it. At this stage, the mouth is not opened. Immediately follow that action with the special treat. Once the cat is comfortable with this, the owner can open the mouth slightly and then give the cat the treat. Gradually, open the mouth more and more, followed by giving the treat. Once the cat’s mouth can be opened as much as is needed for a pill to be placed in the back of the mouth, the owner should quickly stick their finger in, then again give the cat the treat. Finally, give the pill, and follow up with the special treat. Many cats will tolerate mildly aversive medical procedures if they anticipate a special food treat immediately following the procedure.
Medications that do not have a bitter or aversive taste can often be given to horses in their feed. For example, fluoxetine is available in capsules. The horse’s daily dose of fluoxetine can be emptied into their grain, and stirred in. All of the horses that the author has treated this way have readily consumed it.
25.3 Fast-acting Medications
Fast-acting medications can be used on an as needed basis, or daily, depending on the species, the disorder, and the medication. For patients with major anxiety disorders, such as severe separation anxiety or severe storm phobia, fast-acting medications are often used as a supplement to a maintenance medication and behavior modification, especially during the first weeks of treatment. These products are most useful being used on an as needed basis, with no other medication, when the situation that triggers anxiety or fear is uncommon, especially if it can be anticipated in advance. All of them typically work best if given in advance of the fear-inducing stimulus or situation. While the owner’s departure or a visit to the veterinary hospital can be predicted in advance, aversive stimuli such as storms are usually much less predictable. However, modern weather monitoring systems, combined with various apps that can notify an owner on their smart phone or their computer that a storm is likely, have made it much easier to anticipate when a fast-acting medication is needed for a storm phobic patient.
25.3.1 Benzodiazepines
The benzodiazepines comprise the longest used rapid-acting medications for anxiety and fear. They also often promote prosocial behavior. Their anxiolytic effects are due to action in the hypothalamus and cerebrum, facilitating the action of gamma-aminobutyric acid (GABA) in the CNS by binding to GABAA receptors. Clinically, their duration of efficacy varies widely depending on the species, the dose, and whether the medication is given as a single dose or multiple doses.
They are useful for a wide variety of anxiety disorders, including submissive urination and urine marking in dogs, phobias, such as storm phobia and noise phobia, fear of being clipped, separation anxiety, and timidity. While dose recommendations have been offered for diazepam in cats, the author recommends that it not be used in this species due to reports of the drug causing acute hepatic failure and the fact that alternative benzodiazepines are available which have not been recorded as having this adverse effect in cats (Center et al., 1996; Hughes et al., 1996; Park, 2012; van Beusecom et al., 2015). Doses of eight different benzodiazepines for use in dogs and cats are given in Table 25.1. Diazepam doses for parrots, horses, and rabbits are given in Table 25.2.
Table 25.1. Doses of various benzodiazepines for dogs and cats.
| Medication | Dogs | Cats |
| Alprazolam (Xanax) | 0.02–0.1 mg/kg q4h | 0.0125–0.25 mg/kg q8h |
| Chlordiazepoxide (Librium) | 2.0–6.5 mg/kg q8h | 0.2–1.0 mg/kg q12h |
| Clonazepam (Klonopin) | 0.1–0.5 mg/kg q8–12h | 0.015–0.2 mg/kg q8h |
| Clorazepate dipotassium (Tranxene) | 0.5–2.0 mg/kg q4h | 0.5–2.0 mg/kg q12h |
| Diazepam (Valium) | 0.5–2.0 mg/kg q4h | 0.1–1.0 mg/kg q4h |
| Flurazepam (Dalmane) | 0.1–0.5 mg/kg q12h | 0.1–0.4 mg/kg q12h |
| Lorazepam (Ativan) | 0.02–0.5 mg/kg q8–12h | 0.03–0.08 mg/kg q12h |
| Oxazepam (Serax) | 0.04–0.5 mg/kg q6h | 0.2–1.0 mg/kg q12–24h |
Note: All doses given are orally and as needed until the desired effect is reached. The hourly schedules are the maximum frequency at which the medication should be given. As a general rule, start at the lowest dose and titrate upward if needed. See text for further explanation. From de Souza Dantas and Crowell-Davis (2019a), with permission.
Table 25.2. Dose of diazepam for parrots, horses, and rabbits.
| Species | Diazepam dose |
| Parrot | Two drops of 5 mg/ml solution per ounce of drinking water |
| Horse | 10–30 mg q8h |
| Rabbit | 0.1–0.6 mg/kg |
From de Souza Dantas and Crowell-Davis (2019a), with permission.
25.3.2 Trazodone
Trazodone is a serotonin antagonist/reuptake inhibitor that blocks serotonin 2A and 2C receptors, as well as serotonin reuptake. It is given as needed for fear and anxiety, particularly when the animal is in a fear-inducing situation, such as going to the veterinary hospital.
Side-effects recorded in dogs include colitis, vomiting, increased excitement, sedation, increased appetite, and perceived disinhibition (Gruen and Sherman, 2008). Doses for the dog and cat are given in Table 25.3.
Table 25.3. Dose of trazodone given orally for dogs and cats.
| Species | Dose range |
| Dog | 1.7–19.5 mg/kg/day PO (daily or prn) or 1.7–9.5 mg/kg PO q8–24h |
| Cat | 50–100 mg per cat PO prn or 10.6–33.3 mg/kg PO prn |
25.3.3 Sympatholytics
Dexmedetomidine
Dexmedetomidine is a sympatholytic medication for which an oral gel (Sileo) has been FDA-approved for use in dogs with noise phobias. It should be placed on the oral mucosa between the dog’s cheek and gums, ideally 30–60 minutes before an anticipated adverse noise event. If unexpected noises occur and the dog begins to show anxiety, the dexmedetomidine should be given immediately. During a prolonged noise event, such as 4th of July fireworks in the United States, up to five doses can be given with a minimum of 2 hours between each dose (Korpivaara et al., 2017).
Propanolol
Propanolol is a sympatholytic agent, blocking beta-1 and beta-2 receptors. In human psychiatry it is used for situations of acute anxiety, such as test anxiety, performance anxiety in musicians, and stage fright. It has been used in dogs and cats in combination with other medications and behavior modification, but there is little information on its use in veterinary behavioral medicine at this time (Walker et al., 1997).
25.3.4 Opioid antagonists
Opioid antagonists are effective in the treatment of some cases of stereotypic behaviors and obsessive-compulsive disorder in animals. A common hypothesis is that carrying out the stereotypic behavior causes the release of endogenous endorphins, giving the patient a kind of ‘high’. In this way, carrying out the stereotypic behavior would be positively reinforced. However, studies confirming this theory are lacking. If this were actually happening when the patient was given an opioid antagonist, the intensity and/or frequency of the behavior should initially increase, i.e., the so-called ‘extinction burst’ would occur. Instead, animals that respond to this treatment decrease or discontinue the stereotypic behavior almost immediately. This response supports another hypothesis, which is that opioids induce stereotypic behavior. If this were the case, giving the patient an opioid antagonist would be expected to cause a rapid or immediate decrease or discontinuation of the behavior.
25.3.5 Antipsychotics
Antipsychotics block the action of dopamine, which is a catecholamine neurotransmitter that is synthesized from tyrosine obtained via the diet. Dopamine regulates motor activities and appetitive behavior. Low levels of dopamine result in behavioral quieting, depression, and extrapyramidal signs. Excessive dopamine causes psychotic symptoms and the development of stereotypic behaviors. In veterinary medicine in general, antipsychotics are most commonly used to generate temporary decreases in motor activity and/or restraint.
In behavioral medicine, antipsychotics can be useful in cases of intense fear that can lead the individual to harm itself or its environment. However, for such patients it should only be used in conjunction with true anxiolytics, as antipsychotics themselves have little to no anxiolytic effect. In essence, all they do is slow the patient down.
Acepromazine
Acepromazine maleate is probably the most commonly used antipsychotic in veterinary medicine. It should never be used as the sole treatment for fearful or anxious patients. While its use is based upon its slowing down the animal’s movement, there have been multiple incidents of idiosyncratic aggression in both dogs and cats treated with acepromazine (Waechter, 1982; Meyer, 1997). Doses for the more commonly used antipsychotics in dogs, cats, and horses are given in Tables 25.4 and 25.5.
Table 25.4. Doses for antipsychotics for dogs and cats.
| Drug | Canine | Feline |
| Acepromazine | 0.5–2.0 mg/kg PO q8h or prn | 1.0–2.0 mg/kg PO prn |
| Chlorpromazine | 0.8–3.3 mg/kg PO q6h | 3.0–6.0 mg/kg PO |
| Promazine | 2.0–6.0 mg/kg IM or IV q4–6h prn | 2.0–4.5 mg/kg IM |
| Thioridizine | 1.0–3.0 mg/kg PO q12–24h | |
| Haloperidol | 0.05–2.0 mg/kg PO q12h | 0.1–1.0 mg/kg PO |
| Pimozide | 0.03–0.3 mg/kg PO | |
| Clozapine | 1.0–70 mg/kg PO | |
| Sulpiride | 5.0–10.0 mg/kg PO |
IM, intramuscular; PO, orally; prn, use when needed.
From Seibert and Crowell-Davis (2019) with permission.
Table 25.5. Doses of antipsychotics for horses.
| Drug | Dose |
| Acepromazine | 0.02–0.1 mg/kg IM |
| Promazine | 0.4–1.0 mg/kg IV or 1.0–2.0 mg/kg PO q4–6h |
| Haloperidol decanoate | 0.004 mg/kg IM |
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