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
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.
FIGURE 1: Systematic approach to seizure management
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.