The Different Drugs Used to Help Control Canine Idiopathic Epilepsy

Did you know that seizures are one of the most common neurological problems in dogs? Seizures can be caused by many different things, including head trauma, stroke, and poisoning. However, in about 60% of cases, the cause is unknown (known as idiopathic epilepsy). If your dog has been diagnosed with canine idiopathic epilepsy, it's important to know about the different drugs that are used to help control seizures.

In this blog post, we will discuss 4 of the most common long-term anti-epileptic drugs (AEDS) used to treat canine idiopathic epilepsy: phenobarbital, potassium bromide, imepitoin and levetiracetam.

When a dog is first diagnosed with epilepsy, your veterinarian may start them on medication to help control seizures. Although there are no well-researched guidelines for when to start dogs on medication, theconsensus amongst veterinary neurologists is extrapolated from human medicine.

They are as follows;

1. If they have two or more epileptic seizures in a 6 month period, this is called an interictal period.

2. If they have status epilepticus (i.e. a seizure that doesn't stop) or cluster seizures (i.e. several seizures close together)

3. If the postictal signs are especially severe or last longer than 24 hours

4. They are experiencing more seizures that are lasting longer and are becoming more severe.

A recent UK-based study asked general practitioner vets what they prescribed as a first-line medication for dogs with idiopathic epilepsy.

According to the study, Phenobartial was the most common first-line AED,used 86% of veterinarians, followed by imepitoin (11%) levetiracetam (0.8%), and diazepam (0.4%).

Interestingly the same study found that only 53% of first line practitioners discuss additional therapies, such as dietary and avoidance of trigger factors.

Phenobarbital

The most common AED for dogs has existed for over 100 years and controls seizures by depressing the central nervous system. It enhances the activity of the inhibitory neurotransmitter GABA, a neurotransmitter that inhibits nerve cells from firing. Phenobarbitone can affect the metabolism of other drugs such as zonisamide by increasing clearance pathways. This can result in other medications being less effective. Phenobarbital can be used as monotherapy (the only antiepileptic drug), or in combination with other drugs. The most common side effects of phenobarbital are sedation and ataxia (uncoordinated movement). Some dogs may also experience polyuria/polydipsia (increased urination/drinking), hunger, or behaviour changes.

Potassium Bromide

While its mechanism of actin is not fully understood, potassium bromide appears to be complementary to other anticonvulsants (Woodbury et al 1982). It takes 2 -3 months after a dose change for a steady state of medication to be reached, meaning achieving the appropriate dose can be a lengthy process. When giving potassium bromide, it is important to keep the chloride content of the diet stable, as an increase in chloride intake will result in an increase in bromide clearance via the kidneys. It can be used as monotherapy or in combination with other drugs. The most common side effects of potassium bromide are sedation and ataxia. Some dogs may also experience polyuria/polydipsia, hunger, or behaviour changes. There are other side effects more commonly seen when compared to other AEDs, such as vomiting, diarrhoea, and weakness in the back legs. Although these side effects can resolve, it can take months to do so.

Imepitoin

This newer AED works by acting as a low-affinity partial agonist of the benzodiazepine site of the GABA-A receptor, resulting in an inhibitory effect on neurons. It also has a weak calcium channel blocking effect which may contribute to anticonvulsive properties. The International Veterinary Epilepsy Task Force recommends the use of imepitoin as a single therapy in dogs with single generalized recurrent epileptic seizures, but there is insufficient evidence for its use as an add-on AED. The efficacy of imepitoin is similar to that of phenobarbitone in controlling seizures in dogs with single, recurrent generalised seizures. As the frequency of adverse effects is much more likely with dogs treated with phenobarbitone compared to imepitoin, it is gaining popularity as primary therapy in dogs that experience single generalised recurrent seizures (or to put it in another way - dogs that don't experience cluster seizures or status epilepticus). Importantly, although imepitoin may be an appropriate starting medication, if patients continue to seizure through imepitoin, commencing another AED such as phenobarbitone (while gradually weaning off imepitoin) is generally recommended. The most common side effects of imepitoin are sedation and ataxia. Some dogs may also experience side effects such as polyuria/polydipsia, hunger, increased salivation, or behaviour changes.

Levetiracetam

Also known as Keppra, this AED's mechanism of action differs from the others insofar that It is thought to affect the release of neurotransmitters from sypatic vesicles (i.e. their packaging). Levetiracetam can be used as monotherapy or in combination with other drugs. The most common side effects of levetiracetam are sedation and ataxia. Levetiracetam is well absorbed orally but is metabolised quickly compared to other AEDs, lasting around 8 hours in most dogs at cats. Extended-release products are available in some countries. It is generally well tolerated in both dogs and cats. It is often used as an add-on medication, either as a pulse therapy when patients are experiencing episodes of breakthrough seizures or as a long-term medication.

Conclusion

All of these drugs require a prescription from your veterinarian and regular monitoring by your veterinarian or a board-certified veterinary neurologist. If you have any questions about the best medication for your dog, please don't hesitate to ask your veterinarian.

Thanks for reading! We hope this blog post has been helpful in understanding the different drugs used to help control canine idiopathic epilepsy.

References

1. Griffin, S., Stabile, F., & De Risio, L. (2022). A cross-sectional survey of canine idiopathic epilepsy management in primary care in the United Kingdom. Frontiers in Veterinary Science, 9. https://doi.org/10.3389/fvets.2022.907313

2. Bhatti, S. F. M., De Risio, L., Muñana, K., Penderis, J., Stein, V. M., Tipold, A., Berendt, M., Farquhar, R. G., Fischer, A., Long, S., Löscher, W., Mandigers, P. J. J., Matiasek, K., Pakozdy, A., Patterson, E. E., Platt, S., Podell, M., Potschka, H., Rusbridge, C., & Volk, H. A. (2015). International Veterinary Epilepsy Task Force Consensus Proposal: Medical Treatment of canine epilepsy in Europe. BMC Veterinary Research, 11(1). https://doi.org/10.1186/s12917-015-0464-z

3. Tipold A, Keefe TJ, Löscher W, Rundfeldt C, de Vries F. Clinical efficacy and safety of imepitoin in comparison with phenobarbital for the control of idiopathic epilepsy in dogs. J Vet Pharmacol Ther. 2015;38:160–8.

4. Löscher W, Hoffmann K, Twele F, et al. The novel antiepileptic drug imepitoin compares favourably to other GABA-mimetic drugs in a seizure threshold model in mice and dogs. Pharmacol Res 2013;77:39-46. Available at: https://www.vin.com/doc/?id=6145032. Accessed April 6, 2016.

5. Boehringer Ingelheim Vetmedica GmbH. Pexion tablets [summary of product characteristics]. Ingelheim/Rhein, Germany; 2013:23. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/veterinary/002543/WC500140840.pdf. Accessed April 5, 2016.

6. Woodbury DM, Penry J, Pippenger C. Other antiepileptic drugs. In: Woodbury DM, Penry JK, Pippenger CE, eds. Antiepileptic drugs. 2nd ed. New York: Raven Press; 1982:791-801.