Behavioral medication

• Medications commonly used to treat behavioral conditions in dogs and cats are usually antidepressants and anxiolytics that fall into 3 main classes:
  • The benzodiazepines (BZDs: alprazolam, clorazepate Clorazepate, diazepam Diazepam, midazolam Midazolam, oxazepam, clonazepam, lorazepam, temazepam).
  • The tricyclic antidepressants (TCAs: amitriptyline Amitryptiline, nortriptyline, clomipramine Clomipramine hydrochloride, imipramine, doxepin), and
  • The selective serotonin reuptake inhibitors (SSRIs: fluoxetine Fluoxetine hydrochloride, paroxetine, setraline, fluvoxamine, citalopram, escitalopram).
• Increasingly we see patients treated with:
  • Noradrenergic reuptake inhibitors (NRIs: reboxetine).
  • Dual serotonin norepinephrine reuptake inhibitors (SNRIs: venlafaxine, duloxetine).
  • Dual serotonin 2A agonist/serotonin reuptake inhibitors (SARIs: trazadone Trazodone hydrochloride, nefazodone), and
  • Noradrenergic and specific serotonergic antidepressants (NaSSAs: mirtazapine Mirtazapine).
• Less commonly used medications, or those with more restrictive populations likely to benefit include:
  • Monoamine oxidase inhibitors (MAO-Is: selegiline Selegiline hydrochloride).
  • Azapirones (buspirone).
  • Centrally acting alpha agonists which may act as hypotensives, decreasing decrease cardiac output and peripheral vascular resistance (clonidine, guanfacine, medetomidine Medetomidine and dexmedetomidine Dexmedetomidine, all centrally acting alpha2A-adrenergic receptor agonists; dexmedetomidine also affects alpha1A-receptors).
  • NMDA antagonists (memantine).
  • Sympathomimetics (dextroamphetamine, methylphenidate) and
  • Hormonal agents.
• All of these medications cause their effects through modulation of the neurotransmitters serotonin (5-HT), dopamine (DA), noradrenaline/norepinephrine (NA/NE) and/or gamma amino butyric acid (GABA), and their related metabolites (eg the excitatory amino acid glutamate, which becomes GABA). Accordingly, any medication, supplement or dietary constituent that shares a metabolic or synthetic pathway with any of these neurotransmitters or medications can affect the amount of any medications available and their utility.
• Acepromazine (ACP Acepromazine maleate) is not a behavioral medication and should be avoided in patients with behavioral concerns, especially those with heightened noise reactivity. Patients that are noise reactive/phobic and treated with acepromazine will invariably worsen.
• Clients worry about side effects, so it is essential that the veterinary team has an accurate understanding of relevant risk.
  • Common adverse effects of psychotherapeutic drugs are usually caused by a blockage of the muscarinic acetylcholine receptors, which have diffuse connections throughout the brain.
  • These 'common' side effects are actually not very common and generally manifest themselves as transient changes.
  • The most common complaints are related to gastrointestinal function, appetite change, sedation or alterations - usually increases - in heart rate.
  • For the overwhelming majority of patients any side effects will truly be transient, occurring within the first week; however, if any side effect is not transient, clients need to understand that their pet may be experiencing a serious problem.
  • For this reason, it is important to encourage clients to help monitor both their animal's response to the medication, and any side effects that they may have.
• While many benzodiazepines (BZDs) can be sedative, the BZDs now used most commonly (eg alprazolam, oxazepam, clonazepam) are less sedative than diazepam and clorazepate:
  • Because dogs and cats, like humans, can experience a huge range of effects when given a BZD, clients should be encouraged to give any BZD when they can monitor the patient. This means that the first dose or 2 should be given when the client is home and can watch the dog or cat.
  • Clients can test and monitor for side effects, and can learn if a BZD is effective for their pet.
• Because the most severe side effects of TCAs, SSRIs and the more recently popular serotonin 2A antagonist/reuptake inhibitors (SARIs) can involve cardiac affects, clients should and can easily learn to take pulse rates, which may be the first sign of developing serotonin syndrome Serotonin syndrome. Slight increases in pulse rate are not worrisome. Huge, sustained increases in heart rate are problematic. If clients know that their dog's resting heart rate is 65 bpm and with medication this changes to 150 bpm, they can immediately bring this change to their veterinarian's attention. Likewise, if the increase is minor (65 to 75 bpm) the client can take notes and not worry:
  •  For this reason, baseline ECGs are recommended for any patient who has had a history of any arrhythmia, heart disease, prior drug reactions, is on more than one medication, and who may be undergoing anesthesia or sedation.
  • Cats may be more sensitive to cardiac side effects than are dogs, and, minimally, a lead II ECG evaluation for any arrhythmias should be done before treating cats with agents that may affect serotonin.
• Most behavioral drugs are metabolized through renal and hepatic pathways so knowledge of baseline, pre-medication values is essential. Liver dyscrasias and cardiac arrhythmias may not rule out the use of a drug, but knowing that they exist can serve as a guide to dosage and anticipated side effects. Annual laboratory evaluation can help monitor changes in renal or hepatic function that may affect metabolism of behavioral medications. Should changes occur their magnitude can guide alterations (usually decreases) in the dosages of behavioral medication.
• Atypical reactions can occur so for any unexplained or sudden illness, laboratory evaluation is essential. If any rare, but profound alteration in hepatic function occurs, immediate withdrawal from behavioral medicine is an option while the patient receives supportive care. While dogs have been known to die of toxic overdose of their owners' medication, there have been few confirmed cases of death due to behavioral medication prescribed for the dog at therapeutic dosages.
• Educated clients will monitor their pet's better, will be more willing to use medications and behavior modification appropriately, and will be more enjoyable clients for their veterinarian. Clients should receive a complete list of all potential adverse responses and should be encouraged to communicate with the veterinarian at the first sign of any problem. Clients are often very distressed after a behavioral consultation and need a written reminder of situations for which they should be alert.
• This practice of encouraging clients to be active participants in care and monitoring of their pet is extremely helpful in ensuring that we recognize animals with atypical or serious sedative responses so that we can find more appropriate medications with which to treat them.
• All psychotropic medications can interact with other medications. For example, use of TCAs, SSRIs and related drug classes will cause thyroidal values - whether or not supplementation is involved - to read falsely low. It is essential to know about this interaction when evaluating an animal's true thyroid status. This issue is especially germane for dogs, for whom there has been a cyclic vogue for non-specifically treating dogs with behavioral concerns and borderline thyroid values with thyroxin. There is now good evidence showing that most behavioral concerns are not directly associated with any thyroid dysfunction, although such dysfunction may certainly affect behavior.
• Many serotonergic agents are thought to lower thresholds and so are recommended with caution in patients treated with a history of seizures. The story is considerably more complex than this. For both human and dog anxiety, itself, may lower seizure thresholds and so treatment of the anxiety may actually raise the seizure threshold and allow the patient to successfully decrease the amount of seizure medication needed.
• Finally, the client household must be considered when the decision to use behavioral drugs is made. Substance abuse is rampant in humans and some medications used to treat canine and feline behavioral conditions have a high human abuse potential.
• No modern pharmaceutical intervention for veterinary patients with behavioral problems is intended to sedate or 'drug' the dog or cat. If this is the outcome, the patient is experiencing an undesirable effect. Options include discontinuation through weaning, altering dosage or frequency of dosing and/or changing medications.
• The key to understanding usage of psychotropic medications is two-fold:
  • These medications are designed to directly address the underlying anxiety and other neurochemical concerns that are at the root of most behavioral concerns.
  • As supported by every double-blind, placebo-controlled study published, these medications speed the rate at which patients acquire new behaviors through positive reinforcement and behavioral modification. It is likely that this synergistic effect is the result of alterations of neuronal chemistry and molecular biology that favors the translation of new proteins. Accordingly, there is no reason to deprive any patient of medication as part of an integrated, holistic, complete behavioral program of humane intervention.

Nutraceuticals

Pheromone therapy

Further Reading

Publications

Refereed papers

• Recent references from PubMed and VetMedResource.
• De Porter T L, Landsberg G M, Araujo J A, Eithier J L, Bledso D L (2012) Harmonease Chewable Tablets reduces noise-induced fear and anxiety in a laboratory canine thunderstorm situation: a blinded and placebo controlled study. J Vet Behav: Clin Appl Res (7), 225-232.
• Araujo J A, de Rivera C, Ethier J L et al (2010) Anxitane® tablets reduce fear of human being in a laboratory model of anxiety-related behavior. J Vet Behav: Clin App Res 5 (5), 268-275 VetMedResource.
• Frank D, Beauchamp G, Palestrini C (2010) Systematic review of the use of pheromones for treatment of undesirable behavior in cats and dogs. JAVMA 236 (12), 1308-1316 PubMed.
• Rème C A, Dramard V, Kern L et al (2008) Effect of S-adenosylmethionine tablets on the reduction of age-related mental decline in dogs: a double-blinded, placebo-controlled trial. Vet Ther 9 (2), 69-82 PubMed.
• Beata C, Beaumont-Graff E, Diaz C et al (2007) Effects of alpha-casozepine (Zylkene) versus selegiline hydrochloride (Selgian, Anipryl) on anxiety disorders in dogs. J Vet Behav: Clin Appl Res 2 (5), 175-183 VetMedResource.
• Beata C, Beaumont-Graff E, Coll V et al (2007) Effect of alpha-casozepine (Zylkene) on anxiety in cats. J Vet Behav: Clin Appl Res 2 (2), 40-46 VetMedResource.
• Heath S E, Barabas S, Craze P G (2007) Nutritional supplementation in cases of canine cognitive dysfunction - a clinical trial. Appl Behav Sci 105 (4), 284-296 VetMedResource.
• Simpson B S, Papich M G (2003) Pharmacologic management in veterinary behavioral medicine. Vet Clin North Am: Small Anim Pract 33 (2), 365-404, vii PubMed.
• Overall K L (2001) Pharmacological treatment in behavioral medicine: the importance of neurochemistry, molecular biology, and mechanistic hypotheses. Vet J 162 (1), 9-23 PubMed.
• Reich M R, Ohad D B, Overall K L et al (2000) Electrocardiographic assessment of antianxiety medication in dogs and correlation with drug serum concentration. J Am Vet Med Assoc 216 (10), 1571-1575 PubMed.

Other sources of information

• Overall K L (2013) Manual of Clinical Behavioral Medicine for Dogs and Cats, Elsevier, St. Louis.
• Overall K L (2013) Humane Behavioral Care for Dogs: Problem Prevention and Treatment. DVD. Elsevier, St. Louis.

Organizations

• American College of Veterinary Behaviorists (ACVB): www.dacvb.org.
• American Veterinary Society of Animal Behavior (AVSAB): www.avsabonline.org.
• Australian Veterinary Behaviour Interest Group (AVBIG), a special interest group of the Australian Veterinary Association (AVA): www.ava.com.au.
• Companion Animal Behaviour Therapy Study Group (CABTSG): www.cabtsg.org/(affiliated with the British Small Animal Veterinary Association (BSAVA)).
• European College of Animal Welfare and Behaviour Medicine - Animal Welfare Science, Ethics and Law (ECAWBM-AWSEL): www.ecawbm.org.
• Pet Professional Guild (PPG): www.petprofessionalguild.com.
• Veterinary Behaviour Chapter of the Australian and New Zealand College of Veterinary Scientists: www.acvsc.org.au.