Weaving, pawing, and head-nodding may seem like quirky or humorous behaviors to outsiders, but owners of these horses know the truth: stereotypic behaviors negatively affect a horse's quality of life, use, and value. Fluoxetine, sold under various brand names including Prozac, anecdotally reduces the occurrence of stereotypies; however, appropriate dosing needed to “reliably reduce equine stereotypic behaviors” remains to be determined, according to researchers.*
“Experts suggest that stereotypic behaviors develop in horses secondary to stress-related events such as stall confinement, isolation from herdmates or poor herd dynamics, training, and feeding programs,” explained Catherine Whitehouse, M.S., a nutritionist for Kentucky Equine Research. “The incidence or development of stereotypic behaviors generally increases when forage intakes are low and can be exacerbated by feeding large amounts of concentrates.”
Once horses begin displaying stereotypic behaviors, treatment options are extremely limited. Reports suggest that fluoxetine effectively reduces the occurrence of stereotypic behaviors. A study on fluoxetine metabolism, however, shows that fluoxetine behaves differently in horses than in humans.
Fluoxetine is classified as a selective serotonin reuptake inhibitor (SSRI). This type of medication allows the neurotransmitter serotonin to persist in the brain for longer periods of time. In humans, doctors prescribe fluoxetine for a variety of conditions related to anxiety and depression.
Studies show that trazodone, another well-known SSRI, reduces a variety of stereotypical behaviors in horses but causes excitation, aggression, muscle fasciculations, and incoordination. Fluoxetine, on the other hand, appears effective in horses for improving stereotypic behaviors without the side effects noted with trazodone.
These anecdotal reports suggest that horses respond to human doses of fluoxetine, about 125 mg for an average 1,100-pound horse. Despite these anecdotal reviews, veterinarian researchers recently pointed out that without any studies on fluoxetine absorption, metabolism, or elimination, no accurate information exists on appropriate dosing, safety, or effectiveness.
Rather than relying on anecdotal reports for dosing information, the research team recruited healthy, client-owned horses without stereotypical behaviors. In the first part of the study, those horses were administered a compounded fluoxetine paste. Each horse received a single dose of fluoxetine paste (equivalent to 0.25 mg/kg) after being fasted overnight. Blood samples were collected prior to administration, intermittently throughout the first day, and again at two days and seven days following administration.
In the second part of this study, horses were administered fluoxetine (0.25 mg/kg) by mouth once daily for eight weeks.
This study revealed that fluoxetine was more rapidly absorbed and eliminated in horses than in other species; however, once-daily dosing maintained steady circulating drug levels. Because healthy horses were used, the therapeutic efficacy of this dose (0.25 mg/kg) could not be established based on this study. That said, no adverse effects were observed in this population of horses.
“One particularly interesting finding was that the fluoxetine metabolite norfluoxetine was not detectable in horses. In humans, fluoxetine is metabolized to norfluoxetine and both compounds have therapeutic effects,” said Whitehouse. “The fact that no norfluoxetine was found in horses further shows that drug absorption and metabolism differ markedly in horses than other species. As a result, limited recommendations can be made on fluoxetine use in horses based on data obtained in other species.”
Recently, many research groups in human and veterinary medicine report that neurotransmitter levels in the brain, including serotonin, can be modulated via the “gut-brain-microbiome axis.” While the exact mechanisms are not known, preliminary data show that modulating brain neurotransmitters by gut microbiota plays a key role in the pathophysiology of anxiety and depression. As such, manipulating the gut microbiota could provide a novel way to alter neurotransmitter levels in the brain to treat anxiety and depression.
“Episodes of stress can negatively affect digestive health and the development of stereotypic behaviors. Eliminating all potential stressors is not possible, but owners can proactively support digestive health with research-proven digestive buffers,” Whitehouse explained.
Evidence also suggests that high-strung horses may benefit from supplemental magnesium and thiamine by reducing anxiety.
*Waitt Wolker, L.H., C.A. Veltri, K. Pearman, M. Lozoya, and J.W. Norris. 2022. Pharmacokinetics of fluoxetine in horses following oral administration. Journal of Veterinary Pharmacology and Therapeutics 45(1):63-68.
Reprinted courtesy of Kentucky Equine Research. Visit ker.com for the latest in equine nutrition and management, and subscribe to Equinews to receive these articles directly.
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