Lecture Link: Taming the tremors: New options for treating epilepsy

When faced with a patient with epilepsy, we are not often able to confirm the underlying cause and need to consider the risks associated with treatment while still maintaining the pet's quality of life. In his presentation "Advanced treatment options for epilepsy," Michael Podell, DVM, DACVIM (neurology), discussed strategies for instituting antiepileptic drug therapy and provided an overview of several new antiepileptic drugs.1

WHEN TO START ANTIEPILEPTIC THERAPY

The decision to begin therapy with antiepileptic drugs must take into account several factors, such as the risk of recurrence, underlying cause, and side effects of treatment. Antiepileptic drug therapy is indicated when:

1 An identifiable structural lesion is present or the patient has a prior history of brain disease or injury.

2 The patient has experienced status epilepticus (ictal event ≥ 10 minutes).

3 The patient has experienced two or more generalized seizures within a 24-hour period.

4 The patient has experienced two or more isolated seizure events within a six-month period.

5 The patient has experienced prolonged, severe, or unusual postictal periods.

WHICH DRUG TO CHOOSE

When you are deciding which antiepileptic drug to administer, Dr. Podell cautioned that no single drug has been proven to provide a better outcome. Rather, consider the risk of adverse events, dosing frequency, and cost (both of the drug and of monitoring).

The ideal antiepileptic drug has yet to be created, but more options are now available. Antiepileptic drugs are divided into three categories:

• First-generation drugs (e.g. phenobarbital, bromide, benzodiazepines, valproate)

• Second-generation drugs (e.g. gabapentin, felbamate, zonisamide, levetiracetam, pregabalin, lamotrigine)

• Third-generation drugs (e.g. lacosamide, rufinamide).

First-generation drugs

Phenobarbital is still widely accepted as standard of care because of its efficacy and tolerability. Dr. Podell recommends a trough therapeutic range of 15 to 25 µg/ml for dogs and 10 to 20 µg/ml for cats. Trough phenobarbital concentrations can guide dosing adjustments when you use the following formula:

(Desired trough concentration/actual trough concentration) X # mg phenobarbital per day given currently = total # mg phenobarbital/day to give to achieve desired trough concentration

Second-generation drugs

Felbamate may be beneficial in patients with focal seizure activity but require increased vigilance because of the risk of cytopenias and hepatotoxicosis.

Among second-generation drugs, zonisamide has become popular as it is well-absorbed and has been successfully used to manage epilepsy in dogs. This drug requires monitoring of drug concentrations with a therapeutic range of 10 to 40 µg/ml.

Levetiracetam is also well-absorbed in dogs, but there are wide fluctuations in drug metabolism. Drug monitoring to establish individual patient pharmacokinetics is recommended.

Lamotrigine is commonly used in people with epilepsy, but in dogs the drug is converted into a cardiotoxic metabolite, and thus cannot be recommended.

Third-generation drugs

Third-generation antiepileptic drugs, such as lacosamide and rufinamide, show promise in treating some forms of human epilepsy, but there are no clinical data to date regarding their use in veterinary medicine.

HOW DO WE KNOW THE THERAPY IS WORKING?

The goal of successful antiepileptic drug therapy is to reduce or eliminate seizure activity while still maintaining a good quality of life for pets and their owners. Dr. Podell notes that only 60% to 80% of canine epileptic patients are responsive to therapy and that patients refractory to seizure control measures need to be further evaluated to determine whether there is an underlying physiological problem (e.g. underlying brain disease, prior trauma) vs. a drug-related issue (e.g. bioavailability, development of tolerance).

REFERENCE

1. Podell M. Advanced treatment options for epilepsy. Presented at the Annual Meeting of the American College of Veterinary Internal Medicine; June 2012.

This "Lecture Link" summary from the 2012 American College of Veterinary Internal Medicine Forum was contributed by Jennifer L. Garcia, DVM, DACVIM, a veterinary internal medicine specialist at Sugarland Veterinary Specialists in Houston, Texas.

Dr. Jennifer L. Garcia