Treatment plans for the routine and difficult-to-control epileptic (Proceedings)


Treatment plans for the routine and difficult-to-control epileptic (Proceedings)

Deciding on a treatment plan for an animal with seizures depends on a number of factors, including the suspected etiologic cause of the seizures, the frequency and severity of the observed seizures, and the financial constraints or intentions of the owner.

Address the underlying cause

If an underlying cause of the seizures is known or suspected, it should be appropriately addressed, if possible. Thus, animals with hypoglycemia or electrolyte abnormalities may require no therapy other than correction of these deficiencies (or excesses). Likewise, patients with hepatic encephalopathy, hypertriglyceridemia or various intoxications may not require long-term anticonvulsant therapy if the primary disease is appropriately addressed, although they may benefit from shorter-term treatment with these drugs. In some cases, damage to the brain may lead to acquired (probably symptomatic) epilepsy, requiring long-term treatment.

Animals with intracranial diseases also benefit from addressing the underlying condition, although these patients are more likely to require maintenance anticonvulsant therapy. Thus, placement of a ventriculoperitoneal shunt for hydrocephalus, anti-inflammatory and/or antimicrobial medications for meningoencephalitis, surgery or radiation therapy for brain tumors, and other specific therapies address the underlying disease process and may reduce or eliminate the need for anticonvulsant therapy.

Maintenance anticonvulsant therapy

Maintenance anticonvulsant therapy is used as an adjunct in symptomatic epilepsy and is the cornerstone of therapy for patients with idiopathic or probably symptomatic (acquired, cryptogenic) epilepsy. The first question to address is: When to start anticonvulsant therapy? There are no hard and fast rules on this issue, and each patient much be approached individually. However, some guidelines apply. In general, maintenance therapy should be considered if:

     • Seizures are more frequent than once every 6-8 weeks
     • Seizures are obviously increasing in frequency
     • Status epilepticus or cluster seizures occur
     • Seizures last longer than 5 minutes
     • Seizures are very severe or involve aggression towards the owner

The second question to address is: Which anticonvulsant should I choose? Historically in dogs, the two main initial options for therapy have been phenobarbital and (potassium) bromide. These medications are chosen because of their long history of use, apparent efficacy, ease of dosing, favorable pharmacokinetics and inexpensiveness. There is limited evidence to suggest that phenobarbital may be slightly more efficacious as a first line agent in the dog. Diazepam is not effective as a maintenance anticonvulsant in the dog due to a very short elimination half-life, and the development of tolerance within several weeks. Some of the newer anticonvulsant medications can be effective as initial therapy, and the author uses zonisamide and levetiracetam with some frequency as first-line agents in dogs. Zonisamide is particularly attractive in this setting due to its low incidence of side effects and its relatively long half-life, allowing twice daily administration.3 However, published reports of efficacy in this setting are lacking in veterinary patients. Use of these newer drugs has been limited in the past by their expense when compared with traditional anticonvulsants, although generic versions of most of these newer generation drugs are now available at reduced costs. In the cat, phenobarbital (preferred) and diazepam are the historical maintenance drugs of choice. Bromide is an effective anticonvulsant in the cat, but is associated with a very high incidence of inflammatory lung disease, and is not recommended. Diazepam should be used with extreme caution in cats, as it has been associated with idiosyncratic hepatic necrosis after oral administration. Levetiracetam may be a reasonable choice in the cat if phenobarbital is not an option, although the drug must be administered three times daily. There is limited information available on zonisamide in cats, although side effects seem to occur more frequently in this species.

Initial maintenance therapy for epileptic animals

     • Phenobarbital – 2.5-3 mg/kg q 12 hours (Dogs or cats)
     • Potassium bromide – 40-50 mg/kg/day q 24 hours or divided (q 12 hours) (Dogs)
     • Zonisamide – 3-5 mg/kg q 12 hours (Dogs)
     • Levetiracetam – 20 mg/kg q 8 hours (Dogs and Cats)
     • Diazepam – 0.2-1.0 mg/kg q 12 hours (Cats, use with caution)

Phenobarbital is available in generic tablets (15, 30, 60, 90, 100 mg) or suspension (3 and 4 mg/ml) formulations, as is diazepam (2, 5, 10 mg tabs; 1 and 5 mg/ml suspension). Zonisamide is available as 25, 50 and 100 mg capsules. Levetiracetam is available as 250, 500, 750 and 1000 mg tablets and a 100 mg/ml suspension. Bromide is typically compounded from the chemical grade salt, and complexed with potassium (KBr) or less frequently with sodium (NaBr). It should be noted that due to molecular weight differences between the cation, equal amounts of KBr and NaBr do not contain the same amounts of bromide, and therefore have different anticonvulsant potencies (250 mg KBr = 211 mg NaBr). KBr is available from a number of compounding pharmacies. Liquid formulations are preferred over capsules, as they facilitate dosage adjustments, and KBr is best administered with food to reduce gastrointestinal irritation. Dietary salt affects serum levels of bromide, and a constant salt level should be maintained in the diet.