Seizures are the most common neurologic problem encountered in small-animal practice. Primary, or idiopathic, epilepsy—a disorder
characterized by recurrent seizures for which an underlying structural cause is not found—is diagnosed in 25% to 40% of dogs
with seizures.1,2 Affected dogs characteristically have an onset of seizures between 1 and 5 years of age, and successful management requires
lifelong medical attention.
Antiepileptic drug therapy is the cornerstone of treatment for epilepsy, and phenobarbital and potassium bromide are the most
commonly prescribed antiepileptic drugs in veterinary practice. Phenobarbital decreases seizure activity by potentiating the
effect of the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), in neurons. Potassium bromide's antiepileptic mechanism
of action is thought to involve hyperpolarization of the neuronal membrane by the movement of negatively charged bromide ion
via GABA-activated chloride channels.
However, about 20% to 30% of epileptic dogs never attain satisfactory seizure control with these conventional antiepileptic
drugs and are considered refractory to treatment.3 In addition, both drugs have a narrow therapeutic index and a propensity to cause marked side effects. Less than half of
epileptic dogs receiving phenobarbital or potassium bromide maintain a seizure-free status without experiencing drug-related
adverse effects.4 Side effects range from sedation, vomiting, polyuria, polydipsia, and polyphagia to more serious complications such as bone
marrow suppression, hepatotoxicosis, and pancreatitis.
Historically, treatment options for dogs that have responded poorly to conventional antiepileptic drug therapy have been rather
limited. Many of the common antiepileptic drugs used in people with epilepsy are not acceptable alternatives in veterinary
medicine because of a lack of efficacy (valproic acid, oral diazepam) and the potential for toxicosis (lamotrigine).
However, over the last 20 years several novel therapies for epilepsy have been developed, and these new antiepileptic drugs
have improved seizure control and resulted in fewer adverse effects in people. Pharmacokinetic studies on many of these new
antiepileptic drugs have been performed in dogs, and the results support their potential application in canine epilepsy. In
addition, several recently published reports describe the treatment of epileptic dogs with these medications. Thus, veterinary
medicine is seeing an increase in the options available for managing refractory seizures in dogs.
In this article, I discuss the potential use of five newer antiepileptic drugs: felbamate, gabapentin, pregabalin, zonisamide,
and levetiracetam. I also provide a tip on how you can help clients manage cluster seizures at home (see "Sidebar: Home care for cluster seizures").
GENERAL TREATMENT CONSIDERATIONS
FIGURE 1: Systematic approach to seizure management
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Regardless of which drug is used, optimal treatment results are best achieved by adopting a systematic approach to seizure
management (Figure 1). Although guidelines may differ among clinicians, I think that antiepileptic drug therapy is indicated for an animal that
is experiencing more than one seizure a month, has cluster seizures irrespective of frequency, or has any history of status
epilepticus. As a general rule, monotherapy is preferred because it tends to avoid complications that may arise from drug
interactions and may also improve compliance by providing a simple treatment regimen.
Adequate treatment response is assessed based on seizure frequency once steady-state serum drug concentrations are reached
as well as on the severity of side effects. If seizures remain inadequately controlled (more than one seizure a month or the
presence of cluster seizures or status epilepticus) in an animal with serum drug concentrations within the low therapeutic
range and no evidence of medication-related side effects, the dosage of the antiepileptic drug can be increased. When drug
concentrations reach the high end of the therapeutic range or unacceptable side effects develop and the animal still experiences
monthly seizures or clusters of seizures, then the patient is considered refractory to that drug, and an additional antiepileptic
drug should be included in the treatment regimen. This scheme can be followed when considering the use of any antiepileptic
drug, including the conventional antiepileptic drugs as well as the newer drugs discussed below. Unless otherwise noted, all
of the alternative seizure medications can be used in combination with both phenobarbital and potassium bromide.
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