6 Sharon L. Crowell‐Davis and Leticia Mattos de Souza Dantas University of Georgia, Athens, GA, USA The term psychopharmacology derives from three Greek words. Psyche means soul or mind; pharmacon means drug. Finally, the term logos means to study. Thus, psychopharmacology, in a basic sense, is the study of drugs that affect the soul or mind. We are interested in such drugs because psychoactive medications affect the brain’s physiology and endocrinology, consequently causing changes in behavior and motivation. Therefore, these drugs can be beneficial for animals with mental health and behavior problems. They have been used with varying results in human psychiatry for several decades, and their efficacy has improved over time as we have come to better understand the complex interrelationships between brain chemistry, emotional states, and overt behavior. We are also developing an improved understanding of the genetics and neuroanatomy of various major behavior problems such as aggression, major depressive disorder, and bipolar disorder (e.g. Krishnan 1999; Vadodaria et al. 2018). Nevertheless, much remains to be discovered. While a great deal is understood about what happens on cell surfaces, the exact mechanism by which receptors and the molecules that interact with them affect mood and behavior is poorly understood. Progress is being made via in vitro growth of neurons derived from psychiatric patients with specific diagnoses (Burke 2004; Vadodaria et al. 2018). The serotonin production, serotonergic receptor activity, serotonin transporter activity, and other specific chemical activity can then be studied from these in vitro cells derived from known phenotypes (Vadodaria et al. 2018). While we can never truly understand the animal mind, we can measure changes in animal behavior that occur as a consequence of the administration of various drugs that enter the brain. We can also place those changes within the context of species‐typical social organization and communication to interpret what is likely happening in terms of changes in the emotional and motivational state of the animal. The use of psychoactive medications has rapidly been integrated into the practice of veterinary clinical behavioral medicine because they can often be of tremendous assistance in the treatment of the serious behavioral and mental health problems that are routinely encountered in this field. Psychoactive medications can be extremely useful in the treatment of mental health conditions and behavior problems in animals, but it is rare for medication alone to provide a cure. In most cases, treatment is most effective if medication is used in combination with environmental management and behavior therapy, such as desensitization and counterconditioning interventions. The most common protocols for behavior therapy are defined and discussed briefly in this chapter but are not the focus of this book. While data on the effect of psychoactive medications on brain pathologies observed in the pet population are increasing yearly, much of the available data on actual efficacy for specific problems is derived from human psychiatric use and extrapolated to use in veterinary clinical behavioral medicine. When using a medication with little historical use in pets, it must be remembered that sometimes medications have different efficacy and different side effect profiles in different species. A medication that works well in humans may work better or worse in a cat or dog, and those species may exhibit side effects never observed in humans. Some drugs, such as tricyclic antidepressants, are safer in cats and dogs than in humans. Wherever possible, data from studies on the use of a given medication in domestic species are provided. Beyond this, drugs that are commonly used by specialists in veterinary clinical behavioral medicine, but about which there is little published data, are discussed with reference to use in humans. Some medications have been used little or not at all in the pet population, but based on their use in humans, might reasonably be tried in pets that have been refractory to better‐tested treatments when the owner is willing to take the chance that their species of pet will have a side effect that has not been observed in humans. In all cases, the species from which particular information on clinical use of a medication has been derived will be identified. As this book goes to press, the use of most psychoactive medications in veterinary medicine is extra‐label. The only label uses of psychoactive medication for the treatment of behavior problems in animals are Clomicalm (clomipramine) for separation anxiety disorder in dogs, Anipryl (L‐deprenyl) for cognitive dysfunction in elderly dogs, Sileo (dexmedetomidine) for noise aversions in dogs and Reconcile (fluoxetine) for dogs with separation anxiety disorder. Extra‐label use means that the medication has not been approved by the Food and Drug Administration (FDA) for the specific problem and the specific species for which it is being prescribed. Thus, use of Clomicalm for separation anxiety disorder in cats or storm phobia in dogs would be extra‐label use. Use of all other psychoactive medications for any behavior problem on any species constitutes extra‐label use. This does not mean that use of medications other than clomipramine, L‐deprenyl, fluoxetine or dexmeditomidine is contraindicated for behavioral problems in animals or that the extra‐label use of clomipramine, L‐deprenyl, fluoxetine or dexmeditomidine is contraindicated. In veterinary clinical behavioral medicine, the off‐label status of most drugs means that the substantial safety and efficacy trials required by the FDA for on‐label use have not been conducted. In many cases, for economic reasons, such trials will never be conducted, despite substantial scientific evidence that a given drug has a real usefulness, with minimal side effects, for a particular problem in a particular species. There are specific requirements for extra‐label use of any medication, psychoactive, or otherwise. First and foremost, there must be a valid veterinarian‐client‐patient relationship. The veterinarian must have personally examined the patient and, based on their own knowledge of the patient’s physical and behavioral status, determined that extra‐label use of medication is appropriate and may be beneficial. To come to this determination, the veterinarian must conduct a physical exam and take both a medical and behavioral history. While some behaviors cannot be observed in the examination room, objective information about the patient’s behavioral history can be gathered by interviewing the owner and other persons who have personally witnessed the problem. Because of widespread use and some degree of knowledge of psychoactive medications in society at large, it is not uncommon for persons who are not qualified or licensed to make decisions regarding medications to attempt to do so. Dog trainers, behaviorists who are not veterinarians, and others, may attempt to convince a pet’s owner and/or the pet’s veterinarian to use a particular drug that the veterinarian does not feel is appropriate. Likewise, news shows that mention use of a particular drug in a pet may result in many calls to veterinarians in the area requesting that the drug be prescribed. In all cases, it must be remembered that the decision regarding which drug to use for a given problem in a given pet is the veterinarian’s responsibility and therefore the veterinarian’s decision. It is likewise the veterinarian’s responsibility to remain current in her or his understanding of the use of psychoactive drugs. When a prescription is written for a given medication, the veterinarian must have a specific rationale for the use of that medication in that patient, and its use must be accepted under current standards of evidence‐based clinical behavioral medicine. Because some psychoactive medications are used very commonly and to good effect for behavior problems, it can be easy to slip into habits of treating such medications as if their use was on‐label. In all cases of extra‐label use of medication, however, clients should be informed of the extra‐label status of the drug and of what the term extra‐label means. Clients should be informed of known side effects and the risk of novel side effects occurring in their pet. An informed consent statement that describes the extra‐label status of the drug, explains why the medication is being prescribed, lists known side effects, and states the risk of novel side effects can be provided to the client. One copy can be provided to the client to take home for reference and a signed copy kept in the patient’s medical records. When prescribing psychoactive medications, one should keep in mind that some have the potential for human abuse. For example, diazepam, which can be very helpful for a variety of phobias, is a Schedule IV drug that has a rapid onset of effect and is addictive. Methylphenidate, used in dogs with true hyperkinesis, is a Schedule II drug that is sold illegally. It is essential that detailed records be kept of the exact prescription and that the patient be monitored closely for response. Also, the practitioner must follow specific state laws regarding prescribing such medications. For example, in Georgia, as of 2003, U.S. Drug Enforcement Administration (DEA) Class II medications must be prescribed in writing only. Telephone prescriptions can be done on an emergency basis, but there must be a written follow‐up within one week. DEA Class III–IV drugs can have five refills or up to six months’ prescription written. Laws covering these details will vary from state to state and country to country. Some of the drugs discussed in this book cannot be used legally in certain countries. In all cases, it is the veterinarian’s responsibility to be aware of both national and local laws that apply to the individual’s practice. Because of the nature of behavioral and mental health problems in pets, it is often not advisable to provide prescriptions for long periods without rechecking the patient in person. Since progress, behavior therapy techniques, environmental management, and physical health must be monitored, all patients on psychoactive medication should come in for outpatient rechecks regularly for a prescription to be continued. At this time, progress and prognosis are assessed and the medication may be changed, the dose increased or decreased, or the medication be continued as during the previous months. Unlike human medicine, where cost issues are often of low priority when making a decision as to which medication to use, cost is often a significant issue in all areas of veterinary medicine, including clinical behavioral medicine. Large chain pharmacies can often offer significantly lower prices than small, individually operated and owned pharmacies. However, the latter are sometimes the only viable source of special compounding that may be needed for particular patients. The cost of a daily dose can also vary with how much medication is purchased at one time, especially if compounding is required. Often, medication is less expensive if bought in bulk, for example a 90‐day supply as opposed to a 30‐day supply. For cats and parrots, many medications must routinely be compounded. For cats and small dogs, if tablets are available, they can be reasonably split into smaller doses than allowed by the scoring with the use of a pill cutter. For some patients that can be pilled but that refuse to consume flavored liquids, and will even spit them out, compounding into small capsules will be necessary. While initial purchases should be small in order to allow time to determine if the pet does not exhibit serious side effects and does respond positively to the medication, clients may obtain considerable savings over the long term if a bulk purchase is made once long‐term use is expected. Because some psychoactive medications can be expensive, it is recommended that the practitioner is aware of the relative costliness of these medications at pharmacies in their area and via legitimate mail order pharmacies and that clients contact multiple pharmacies to get price quotes for their specific prescription. Specific information on drug selection will be given in the chapters on various classes of drugs; however, there are certain general considerations that will be discussed here. First, it is important to remember that our understanding of drug selection for specific behavior problems is changing rapidly as new clinical trials are completed and studies are published. Thus, some statements made in this book will become outdated as a result of new research findings. It is important for the practitioner to keep up to date with research publications. Each patient is a unique individual. At this time, we can only choose what to use based first on the species, the diagnosis, and the health status of the individual patient in a combination of evidence regarding the efficacy of various medications for the particular problem being treated. However, if the first medication used is not effective or generates unacceptable side effects, it is not necessarily the case that no medication will work. Sometimes a different medication in the same class of drugs will work well, even if the first medication was ineffective. Sometimes a medication from a totally different class is required. Sometimes combinations or augmentation are required. Using combinations in particular requires that the clinician understand exactly how each medication works in the brain so that overdosing and adverse drug interactions do not occur. Details of using combinations of drugs are discussed in Chapter 19, as well as throughout the discussion of specific medications. When choosing a drug, selectivity of mechanism is an issue that has at times been considered advantageous in human psychiatry. However, the topic is controversial and will not be discussed in depth in this book. In general, a potential advantage to multiple mechanisms of action in a single drug, for example, norepinephrine reuptake inhibition and serotonin reuptake inhibition, is possible increased robustness of efficacy. This presupposes that both or all of the multiple mechanisms of action in some way benefit the particular patient’s problem. A potential problem is a greater possibility of multiple side effects. Better decision‐making protocols on this issue will be more feasible when very exact relationships are discovered between specific behaviors or behavior problems in a given species and a particular molecular action in the brain. The following should always be considered when choosing a medication:
Introduction to Clinical Psychopharmacology for Veterinary Medicine
Introduction
Prescribing in the United States: The Animal Medicinal Drug Use Clarification Act (AMDUCA 1994)
Cost
Drug Selection
Medicating the Patient
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