By Narda Robinson, DO, DVM
As their families’ lifestyles and work habits continue to evolve, many dogs find themselves cooped up in a home or apartment with little to do for long periods of time. Lack of mental stimulation and too little exercise can predispose dogs (and humans, and cats, and others) to mental and emotional disturbances.
This can lead to physical problems as well as unwelcome and possibly destructive behaviors. In addition to other measures, some folks may seek help through medication or herbal treatment for their dogs.
The American Society for the Prevention of Cruelty to Animals (ASPCA) lists on its website four main classes of medications typically used to address behavior problems in dogs.[i] These include benzodiazepines, monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), and selective serotonin reuptake inhibitors (SSRIs).
They may be recommended along with behavioral change training for conditions such as general timidity, separation anxiety, compulsive behavior, thunderstorm or noise event phobias, and cognitive decline.
The value of pharmaceuticals rests on their relative reliability in results, manufacturing quality and risks. Before instituting a pharmacologic regimen to address problematic anxiety, though, a veterinarian can and should disclose the relative safety and benefits of one or more classes of compounds so that the client can make the most informed decision about the course forward.
Benzodiazepines, for example, may cause disorientation and memory loss in high doses and even lead to vomiting. Some patients may exhibit paradoxical increases in anxiety.
TCAs can lead to water retention and weight gain, as well as dry mouth, tachycardia and changes in elimination habits that raise the risk of incontinence.
MAOIs interact with tyramine, tryptophan and dopamine which, when intermixed, may induce a hypertensive crisis. A variety of dairy products, meat, fish, fruits, and vegetables contain high levels of these chemicals.
While relatively safer than TCAs or MAOIs, overdose of SSRIs manifests as tremors, muscle rigidity, hyperthermia, seizures, ataxia and diarrhea.[ii] The likelihood of adverse events increases when dogs have liver or kidney disease because reduced metabolism and excretion of these drugs will raise circulating levels.[iii]
Worried about having potential problems with medications, owners of these dogs may seek less conventional methods to address anxiety and improve their dogs’ (as well as their own) emotional well-being.
Used alone or in combination with drugs and counseling, phytopharmacologic options are becoming increasingly an attractive alternative.
The list of plant-based approaches for emotional health is long and growing; unfortunately, the list of scientific papers within the medical literature is nearly non-existent regarding how they would work in dogs and for which conditions.
Considering that, educating clients about how herbal measures compare to pharmaceuticals in dogs in terms of effectiveness and side effects is nearly impossible. That said, however, some information has surfaced regarding the effects of psychoactive herbs on humans as well as the interactions that can result when mixed with medications.
Peruse the anxiety product aisle of even big box pet stores, and one will find several herbal-nutraceutical-homeopathic options to treat anxiety and phobias in dogs. Many of these agents contain extracts of popular plants such as St. John’s wort (SJW), valerian, lavender and even hemp.
Each herb alone has a number of psychoactive properties, and many times manufacturers mix them together to pack a more powerful plant-based punch.
Plants differ in their pharmacologic effects from medications by hosting countless numbers of potentially active agents. Few have been characterized as to their pharmacokinetic and pharmacodynamic profiles. As a result, the effects of a whole plant extract may deliver myriad effects on the central nervous system that are difficult to tease out according to chemical components.
For example, an extract of SJW, one of the most commonly appearing herbs in canine stress and anxiety mixtures, exhibits affinity to adenosine, serotonin, benzodiazepine and gamma-amino butyric acid receptors. It can also inhibit monoamine oxidase.
In addition to the slew of mechanisms each plant product manifests, borne by the complexity of chemical constituents harbored in every herb, extracts differ between manufacturers in their amount of known active agents.
For SJW, suppliers may standardize the amount of hypericin from batch to batch. This allows the consumer to compare one product with another in terms of the amounts of hypericin listed on the label. That said, however, many other potentially relevant constituents exist within SJW, such as hyperoside, hyperforin, xanthones, tannins and more.
And then, there are interactions to consider.
SJW has a well-earned status as the plant world’s poster child for causing herb-drug interactions. It does so by interfering with the liver’s ability to metabolize medications through its induction of cytochrome P450 isoenzymes.
It also increases the activity of the transport protein P-glycoprotein.[iv]
Pharmacokinetically, SJW interacts with cyclosporine, theophylline, digoxin, oral contraceptives, warfarin, HIV protease inhibitors, HIV non-nucleoside reverse transcriptase inhibitors and anticonvulsants such as carbamazepine, phenobarbitone and phenytoin.
Pharmacodynamically, SJW can potentiate serotonin concentrations when administered in conjunction with SSRIs and triptans, which are recommended for migraines in humans.
The ability of SJW to inhibit serotonin reuptake as well as amplify the effects of pharmaceutical SSRIs puts patients at risk for central serotonin syndrome. This syndrome results from both central and peripheral serotonergic hyperstimulation.
It may manifest as mental status alterations, gastrointestinal upset, headache, myalgias, restlessness, tremor, and autonomic instability.[v] Canine caregivers who augment their dog’s Prozac with a natural product saturated with SJW could see a worsening of signs they may attribute to behavioral dysfunction or internal illness.
They may seek veterinary intervention, not recognizing that the problem stems from an interaction between the supplement and the drug. If the client fails to volunteer information about adjunctive alternatives she is giving or if the dog’s doctor neglects to ask, this could result in costly testing and delay of diagnosis of the disorder.
What’s needed to remedy this situation? Education and research.
Whether or not they back the practice, medical and veterinary schools need to educate students about herbal benefits, risks and potential interactions with medications as well as promote research in botanical medicine.
Herbs are here to stay. Their presence within pharmacies and pet product lines is increasing steadily. Isn’t it time that veterinarians study and learn how they work?
[i] ASPCA. Behavioral medications for dogs. Accessed at https://www.aspca.org/pet-care/virtual-pet-behaviorist/dog-behavior/behavioral-medications-dogs on 05-27-15.
[ii] Fitzgerald KT and Bronstein AC. Selective serotonin reuptake inhibitor exposure. Top Companion Anim Med. 2013; 28(1):13-17.
[iii] Wismer TA. Antidepressant drug overdoses in dogs. Accessed at http://www.aspcapro.org/sites/pro/files/e-toxbrief_0700.pdf on 05-27-15.
[iv] Henderson L, Yue QY, Bergquist C, et al. St. John’s wort (Hypericum perforatum): drug interactions and clinical outcomes. J Clin Pharmacol. 2002;54:349-356.
[v] Lantz MS, Buchalter E, and Giambanco V. St. John’s wort and antidepressant drug interactions in the elderly. J Geriatr Psychiatry Neurol. 1999;12:7-10.
Originally published in the July 2015 issue of Veterinary Practice News. Loved this article and want to see more like it? Then subscribe today!