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Epilepsy management – which medications should I use first?

A common enquiry our technical team receives regards decision making in therapeutic choices for managing canine epilepsy. With various medications available, it can sometimes be challenging to know when to initiate treatment, which medication to use first and what should be used if an adjunctive medication is required.

Deciding when to treat?

Based on the criteria outlined in the IVETF guidelines1, treatment for epilepsy is recommended when:

  • Interictal period is ≤ 6 months
  • Severe seizure types – cluster seizures or status epilepticus
  • Severe post-ictal signs (e.g., aggression, blindness) or where post-ictal signs persist beyond 24 hours
  • The seizure frequency +/- duration +/- severity is increasing over 3 interictal periods

 

What to use as a first line option?

The current licensed options for monotherapy treatment of epilepsy in dogs include; phenobarbital, imepitoin and potassium bromide*.

The ACVIM panel have graded anti-epileptic drugs from A-D based on evidence from the literature and clinical expertise2.

For monotherapy use, phenobarbital and imepitoin were highly recommended and considered effective (grade A) by the panel and thus these should be the first line choices for most patients with epilepsy.

Imepitoin is indicated for generalised seizures due to idiopathic epilepsy. Phenobarbital is licensed for generalised epilepsy in dogs and therefore can be used for the management of both structural and idiopathic epilepsy. Phenobarbital is also considered efficacious for treatment of severe seizures, cluster seizures and status epilepticus, whereas imepitoin should not be used as a primary treatment for cluster seizures or status epilepticus. A recent study demonstrated better outcomes with phenobarbital treated dogs compared with a group receiving imepitoin3.

Both phenobarbital and imepitoin are contraindicated in severe hepatic insufficiency, therefore potassium bromide, which is not metabolised by the liver, is a good option for patients with hepatic insufficiency. Potassium bromide received grade B (moderate recommendation and most likely to be effective) by the ACVIM panel. One study found that 74% of dogs experienced a 50% or greater reduction in seizure frequency with potassium bromide monotherapy4.

In patients with serious renal insufficiency, all three options are contraindicated and the decision to use should be based on a risk: benefit analysis by the attending veterinarian on a case-by-case basis.

Levetiracetam and zonisamide received a low recommendation (grade C) by the ACVIM panel and Primidone was not recommended (grade D). None of these drugs are licensed for treating canine epilepsy.

 

What to use as an adjunct treatment option?

Some patients will require polytherapy to optimally manage their epilepsy, with 20-40% of dogs reported to be refractory to monotherapy (with phenobarbital)5. In these cases, adjunct treatment with an additional anti-epileptic medication is required.

Potassium bromide has the best level of evidence based on the ACVIM panel recommendations2 for adjunct therapy (grade B) and is licensed for this indication in dogs. Phenobarbital also received grade B, however with a lower level of evidence for adjunct therapy. Given that the majority of dogs requiring a second line anti-epileptic medication will be receiving phenobarbital as a first line option, potassium bromide is an optimal choice for adjunct therapy, particularly as it works synergistically with phenobarbital.

Levetiracetam and zonisamide also received grade B by the ACVIM panel, but neither of these drugs are licensed for use in dogs. Imepitoin received a low recommendation (grade C) for adjunct therapy and is not licensed for this indication. Primidone was not recommended (grade D).

Grade of ACVIM Panel recommendation2:

A: High recommendation and likely to be an effective treatment

B: Moderate recommendation and most likely to be effective treatment

C: Low recommendation and may not be effective treatment

D: Not recommended for treatment and may be ineffective and/or dangerous to the patient

*not all formulations of potassium bromide are licensed for monotherapy use, some are only licensed for adjunct therapy.

References:

  1. Bhatti, S. F., et al. (2015). International Veterinary Epilepsy Task Force consensus proposal: medical treatment of canine epilepsy in Europe. BMC veterinary research, 11, 176.
  2. Podell, M., Volk, H., Berendt, M., Löscher, W., Muñana, K., Patterson, E. and Platt, S. (2016), 2015 ACVIM Small Animal Consensus Statement on Seizure Management in Dogs. J Vet Intern Med, 30: 477-490.
  3. Stabile, F et al. (2019) Epileptic seizure frequency and semiology in dogs with idiopathic epilepsy after initiation of imepitoin or phenobarbital monotherapy. The Veterinary Journal 249: 53-57
  4. Boothe DM, Dewey C, Carpenter DM (2012). Comparison of phenobarbital with bromide as a first-choice antiepileptic drug for treatment of epilepsy in dogs. J Am Vet Med Assoc, 240(9):107
  5. Thomas W. B. (2010). Idiopathic epilepsy in dogs and cats. The Veterinary clinics of North America. Small animal practice, 40(1), 161–179.