For Rabbits that won’t relax at the vets, meds may provide stress relief…

While visiting the vet can be stressful for any animal, something as seemingly simple as a routine checkup tends to trigger more anxiety in rabbits than many other species. As a prey species, rabbits are also more susceptible to unpleasant physiological effects of stress than other animals.

“Rabbits are already more high stress, so coming into a vet clinic where there are other species around and unfamiliar noises can be very stressful for a prey species,” said Dr. Miranda Sadar, assistant professor and head of the exotic, avian, and zoological medicine service at the James L. Voss Veterinary Teaching Hospital.

A stressed-out rabbit is particularly prone to gastrointestinal stasis, a condition where the gastrointestinal tract slows down or stops, resulting in decreased appetite and fecal production. Gastrointestinal stasis can be brought on by disease, pain, or stressful events.

“Gastrointestinal stasis is an emergency for a bunny, and a lot of owners don’t realize when their bunny is going to go into stasis, or when they already have,” Sadar said. “By the time you see clinical signs of gastrointestinal stasis, it’s because it’s already happening.”

Preventing gastrointestinal stasis with gabapentin

To help make unfamiliar situations – including vet visits – more tolerable for rabbits, Sadar led a two-part study to evaluate the use of gabapentin, a drug traditionally used to treat nerve pain and seizures. Others involved in the study include faculty members Dr. Khursheed Mama, Dr. Lon Kendall, and Sangeeta Rao, Ph.D., as well as resident Dr. Mollie Burton, veterinary student Rachel Conway, and D.V.M. alumnus Dr. Noah Mishkin. Gabapentin has been evaluated in cats and dogs to decrease stress associated with veterinary visits, so seeing if it could do the same for rabbits seemed like a natural next step.

“We considered a number of different drugs,” said Mama, professor in the anesthesia and pain management service at the Veterinary Teaching Hospital. “There was a little information already available on gabapentin and its use in rabbits that indicated potential viability, so it seemed like the best choice for further study.”

The first, pharmacokinetic portion of the study measured two different doses of gabapentin – a high dose and a low dose – to determine which amount was best absorbed in the blood over time. The team found that the higher dose didn’t absorb any better than the lower dose, and that the peak level of gabapentin in the bloodstream with both doses was about two hours after administration of the drug.

Using the low dose of gabapentin identified in the first part of the study and targeting activities for around two hours after gabapentin intake, a behavioral study was performed to see if the drug had any effect on rabbits’ behavior while in a simulated veterinary visit.

While data are still being analyzed, preliminary results of the study seem promising. Rabbits receiving the low dose of gabapentin seem a bit more relaxed, with no obvious adverse effects. Because of the findings of the study, clients of the Veterinary Teaching Hospital who own rabbits, and even guinea pigs, have been offered the option to use gabapentin prior to a stressful event. So far, their impressions are positive.

“Clients who have been using gabapentin give it to their rabbit two hours before a stressful event is going to occur,” Sadar said. “Whether that ‘stressful event’ is the car ride to the clinic or the actual appointment time for the vet visit.”

Smooth sailing with gabapentin

The study was funded in part by Cindy Fisher and Steve Good, longtime clients of the exotic, avian, and zoological medicine service at the hospital. While their two rabbits, Randy and Seth, don’t get particularly stressed out going to the vet, they still felt the project was an important research effort to support.

“Our rabbits don’t really get stressed going to the vet, but I know a lot do,” Fisher said. “Supporting the study seemed worth doing for rabbits.”

It wasn’t until after they brought Randy along on a 900-mile trip to Illinois that Fisher remembered the study and that gabapentin could be a huge help in keeping the Holland Lop calm while on the road. Their next trip out to Illinois – with both rabbits – was an entirely different experience.

“Every time we’d stop, I’d offer them veggies and they’d come right out of their carrier and gobble them up. It was shockingly wonderful, having rabbits wanting to eat on a trip,” Fisher said. “It was a great stress reliever for us and clearly for both Randy and Seth.”

A veterinary visit – and the car ride to the clinic – doesn’t have to be a stressful situation for a rabbit. While it’s important to try to keep bunnies away from stressful stimuli as much as possible, vet visits are an essential part of their care, and medications like gabapentin can be a helpful tool to keep anxiety at bay when you have to take your pet to the vet.

Source: Colorado State University; College News

Abstract from the 1st part of the study to compare low dose (25mg/kg and high dose 50mg/kg) Gabapentin -
Background - Gabapentin is used to treat seizures, neuropathic pain, and anxiety. Currently, dosage recommendations for rabbits are extrapolated from other species. The objective of this study was to determine the pharmacokinetics of gabapentin after single, oral administration in domestic rabbits.
Methods - A randomized, crossover study was performed in male (n = 3) and female (n = 3) rabbits after administration of either 25 or 50 mg/kg gabapentin orally. Plasma concentrations of gabapentin were measured at 0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12, 24, and 48 hours post-administration via liquid chromatography.
Results - Mean maximum plasma concentrations were 17.70 and 16.83 µg/mL for the 25 and 50 mg/kg doses, respectively. Mean times to maximum plasma concentration were 1.75 and 1.5 hours, and mean terminal half-lives were 10.2 and 9.44 hours for the 25 and 50 mg/kg doses, respectively. No adverse effects observed at either dose.
Conclusions and clinical relevance - A single oral dose of gabapentin at 50 mg/kg did not result in higher plasma concentrations compared to the 25 mg/kg dose and no differences were observed between males and females for either dosing group (P > 0.9).
Source: Pharmacokinetics of gabapentin after single, oral administration in domestic rabbits (Oryctolagus cuniculus)

Abstract from the 2nd part of the study as cited in this article -
Stress in rabbits (Oryctolagus cuniculus) may influence veterinarians' ability to assess their health and can lead to complications such as gastrointestinal hypomotility and poor anesthetic outcomes. Gabapentin has been used as an anxiolytic in various species, but little information is available on its use in rabbits. To assess the effect of gabapentin on stress in rabbits, 5 female and 3 male New Zealand white rabbits, aged 8-12 months, weighing 3-4.5 kg, were administered a single dose (25 mg/kg) of oral compounded gabapentin. Effects on individual behaviors and selected physiologic parameters were assessed by a blinded observer using a human intruder test and tractability score (summed total 0-8, most to least tractable). Heart and respiratory rate, rectal temperature, body weight, and fecal output were also recorded. Baseline measurements for each rabbit were assessed immediately prior to gabapentin administration, and at 1, 2, and 4 hours post-administration. With this method rabbits acted as their own concurrent control group. Rabbits were assessed at 7 AM, 11 AM, and 3 PM. Data were analyzed as continuous, binary, and continuous nonparametric (P ≤ .05). No significant differences in physiologic parameters were observed between baseline and the post-administration timepoints. Fecal output was reduced similar to baseline measurements. Behaviors pressing down decreased (at 2 and 4 hours; P = .05 and P = .013, respectively) and approaching human increased (at 2 hours; P = .022) post-gabapentin compared to baseline. Tractability scores were improved at the 2-hour timepoint compared to baseline (Friedman P = .0461; Wilcoxon P = .0413). These results suggest gabapentin 25 mg/kg orally decreased reactivity with a peak effect at 2 hours, without significant effects on measured physiologic parameters. Oral gabapentin in rabbits should be considered to reduce stress in the presence of humans and to facilitate handling.Copyright © 2023 Elsevier Inc. All rights reserved.
Source - Behavioral and Physiologic Effects of a Single Dose of Oral Gabapentin in Rabbits (Oryctolagus cuniculus).

Further reading -
Stability of gabapentin in extemporaneously compounded oral suspensions.
Dose rates for Gabapentin use in Rabbits is discussed here - Pain Management in Rabbits; More than just Meloxicom

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