Medication is an essential part of treatment for many behavioral problems in combination with environmental management, behavior modification and monitoring. The only licensed veterinary behavior drugs include clomipramine and fluoxetine for separation anxiety, selegiline for cognitive dysfunction and emotional disorders, and dexmedetomidine oromucosal gel and imepitoin for noise phobias. Most medications used in the treatment of pet behavior problems are the off-label use of these medications or human drugs, most of which have only been assessed in open label and retrospective case studies.

There are no behavioral medications licensed for canine aggression. What medication does is to help to alleviate the underlying fear, anxiety, arousal, panic, impulsivity, reactivity, and hyperactivity, normalize the pet’s mental state, improve the pet’s emotional health, and create an environment in which the pet can learn and behavior can be modified.

Drugs do not change the pet’s relationship with the stimulus. However, when combined with prevention, training, and reward-based behavior modification, medication plays an integral role in reducing fear, anxiety, and stress to improve problem behavior. The selection and use of each drug requires a sound understanding of its indications, mode of action, adverse effects, contraindications and potential drug interactions. For drugs that increase serotonin, counsel owners to monitor for serotonin syndrome (respiratory, cardiovascular, neurological and gastrointestinal signs) for which increased heart and respiratory rate might be early signs. Before dispensing medications, a CBC, biochemical profile and thyroid status should be evaluated to diagnose medical conditions that might be contributing to the signs and as a baseline for future comparison.

Canine Aggression

For the treatment of aggression related to fear, anxiety, reactivity and impulsivity, drugs that enhance serotonin transmission including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCA) are most commonly used. Adjunctive medication to further reduce anxiety either for situational or ongoing use include benzodiazepines, trazodone, imepitoin, beta-blockers, alpha-2 agonists, and clonidine.

[Editor note: Two extraneous paragraphs have been deleted from the originally published version. 8/23/23]

In addition, natural products including dog appeasing pheromone, and nutraceuticals and diets containing l-theanine, alpha-casozepine, valerian, GABA, and melatonin might also be considered adjunctively for improved control of anxiety and reactivity. While drugs are most commonly dispensed when behavior problems are severe or ongoing, early intervention is best as each recurrence further intensifies the problem.

SSRIs and TCAs

SSRIs particularly fluoxetine are most commonly used to reduce reactivity, impulsivity, and some forms of fear and anxiety, as well as to improve trainability and address the dog’s behavioural well-being. SSRIs are selective in blocking the reuptake of 5HT1A into the presynaptic neurons. For fluoxetine, decreased appetite is the most common side effect. Fluvoxamine, paroxetine, sertraline, citalopram and escitalopram are also options. Paroxetine is moderately anticholinergic. Due to their effects on the hepatic cytochrome P450 enzyme system, delayed breakdown and increased levels of concurrent drugs must be considered.

Tricyclic antidepressants (TCAs) have differing effects on blocking the reuptake of both serotonin and noradrenaline and in their anticholinergic and antihistaminic effects which may contribute sedation, urine and stool retention. Clomipramine and amitriptyline may be useful in controlling underlying anxiety and impulsivity associated with aggression. Clomipramine is the most potent of the TCAs in blocking the reuptake of serotonin with less profound effects on noradrenaline reuptake. Noradrenaline reuptake inhibition might be useful in dogs with generalized anxiety and hypervigilance.

Side effects might include gastrointestinal upset, increased agitation, and the serotonin effects. While antidepressants reach peak plasma levels within hours, reuptake inhibition may induce down-regulation of postsynaptic receptors that are responsible for clinical effects. Therefore, 4 weeks or longer is generally recommended to fully assess therapeutic effects. When behavior is stable for at least two months, gradually wean to determine if the medication can be discontinued or the dose lowered; however, long-term use may be required.

Serotonin Agonist Reuptake Inhibitor (SARI)

Trazodone is an SARI which blocks serotonin receptors and serotonin reuptake. In humans, it has anxiolytic, antidepressant and anti-compulsive applications and is commonly used together with SSRIs and TCAs. It is also used for insomnia. Because of its potential calming effects after each dose, it may be used a) as needed use prior to fear-evoking events, such as with noise phobias or separation anxiety, either alone or together with ongoing SSRIs or TCAs; b) as needed or short-term treatment for behavioral calming, such as car rides, veterinary visits and post-surgical confinement; or c) as adjunctive ongoing therapy with SSRIs or TCAs to reduce arousal, reactivity and anxiety.^1,2 Side effects include lethargy, gastrointestinal signs, mild sedation, and potential serotonin effects.

Anxiolytics

Buspirone (an azapirone) is a serotonin (5HT1) partial agonist. It is used for mild fear and anxiety or to augment serotonin in combination with an SSRI or TCA. It is non-sedating, does not stimulate appetite, does not inhibit memory and has minimal side effects, other than gastrointestinal upset and potential serotonin effects. It takes a week or more to reach effect.

Benzodiazepines potentiate the effects of (GABA), an inhibitory neurotransmitter. They cause a decrease in anxiety, hyperphagia, and muscle relaxation. They can be used alone or adjunctively on an as needed basis or for ongoing therapy alone or in conjunction with an SSRI or TCA.³ They may cause paradoxical excitability, increased activity, sedation and may have an amnesic effect. Alprazolam may be particularly useful for panic. Benzodiazepines may increase appetite for counterconditioning and reward training.

Alpha-2 agonists, including clonidine and dexmedetomidine oromucosal gel (OMGl), bind to presynaptic alpha-2 receptors in the locus coeruleus to inhibit the release of noradrenaline to reduce sympathetic response, and for analgesia, and sedation. Bradycardia, hypotension, ataxia and sedation may be seen at higher doses. Dexmedetomidine OMG is licensed in some countries for use in noise phobias at 125 micrograms/m². The product might be given to the dog 30–60 minutes prior to a fear evoking event such as car rides or veterinary visits and repeated every 2 to 3 hours (up to 5 times as necessary).⁴ Dogs should be pre-conditioned to dosing with the syringe. Clonidine has been used in combination with ongoing SSRIs for situational use or for repeated adjunctive use in fear or territorial aggression, separation anxiety, or noise phobias.⁵

Beta blockers, such as propranolol and pindolol, were developed for the treatment of cardiac disease in humans. As they inhibit the action of noradrenaline, they may reduce physiologic signs of anxiety (heart rate, respiratory rate, trembling) and may inhibit the consolidation of memory in fear evoking situations.

Gabapentin

Gabapentin is an anologue of GABA, but does not act to bind GABA. Its anxiolytic effect is believed to be due to activation of calcium channels in the amygdala to block the effects of glutamate and reduce excitatory transmission. Peak levels are seen about 90 minutes after dosing. Gabapentin is used for complex partial seizures as an adjunct in seizure control and for neuropathic pain. Adverse events include ataxia and sedation on initial dosing. Sedation, particularly at higher doses may be useful prior for fear evoking events such as car travel, veterinary visits and noise aversion. Gabapentin might be used adjunctively with serotonin reuptake inhibitors or tricyclic antidepressants on an ongoing basis to help control or reduce reactivity and arousal.

Selegiline is an MAO inhibitor for use in cognitive dysfunction in dogs, which has also demonstrated an effect on emotional disorders in which prolactin levels might be elevated.⁶

Drug doses

References

1.  Gruen M, Sherman B. Use of trazodone as an adjunctive agent in the treatment of canine anxiety disorders; 56 cases (1995–2007). J Am Vet Med Assoc. 2008;233:1902–7.

2.  Gilbert-Gregory SE, Stull JW, Rose M, et al. Effects of trazodone on behavioral signs of stress in hospitalized dogs. J Am Vet Med Assoc. 2016;1281–91.

3.  Herron M et al. Restrospective evaluation of the effects of diazepam in dogs with anxiety-related behavior problems. J Am Vet Med Assoc. 2008;233:1420–4.

4.  Ogata N, Dodman NH. The use of clonidine in the treatment of fear-based behavior problems in dogs: an open trial. J Vet Behav. 2011;6:130–7.

5.  Korpivaara M, Laapas K, Huhtinen M, et al. Dexmedetomidine oromucosal gel for noise-associate acute anxiety and fear in dogs: a randomized double-blind placebo-controlled clinical study. Vet Rec. 2017;180:356.

6.  Pageat P, Lafont C, Falewee C, el al. An evaluation of serum prolactin in anxious dogs and response to treatment with selegiline or fluoxetine. Appl Anim Behav Sci. 2007;105:342–350.