A newer-generation drug to treat canine idiopathic epilepsy

Seizure control is unsatisfactory to pet owners in about 1/4 to 1/3 of dogs treated with phenobarbital or bromide for idiopathic epilepsy. Although new antiepileptic drugs developed for people may be considered to treat epilepsy in dogs, safe and effective alternative drugs for dogs with refractory epilepsy remain scarce.

A recent study published in the Journal of the Veterinary Medical Association assessed the tolerability and short-term efficacy of oral administration of pregabalin as an adjunct to phenobarbital, potassium bromide or a combination of phenobarbital and potassium bromide in dogs with poorly controlled suspected idiopathic epilepsy.1 Pregabalin's mechanism of action is uncertain. High affinity for the alpha2-delta site subunit of voltage-gated calcium channels in the central nervous system may be involved in pregabalin's antiseizure effects.

The authors conducted the open-label noncomparative clinical trial in 11 dogs.1 Dogs eligible for inclusion in the study had satisfied the criteria for idiopathic epilepsy (onset of seizures between 1 and 5 years of age, normal neurologic status during the interictal period and normal blood biochemical analysis) and had poor control with the standard treatment of phenobarbital, potassium bromide or a combination of both. Criteria for poorly controlled seizures were based on frequency of two seizures a month despite therapeutic steady-state plasma concentrations that were in the therapeutic range of phenobarbital, potassium bromide or both. Pregabalin was given three times a day orally, starting at 2 mg/kg to avoid oversedation and then raised gradually to the maximum tolerated dose of 3 to 4 mg/kg.

Nine of the 11 dogs had cluster seizures. Owners of two of the dogs withdrew their dogs from the study at day 38 after the owners considered the treatments to be ineffective and the adverse effects (polyphagia, polyuria, polydipsia, pelvic limb ataxia) to be intolerable. In addition, a dog that received both phenobarbital and potassium bromide developed clinical signs consistent with severe pancreatitis after it ingested garbage as the study concluded. The dog was euthanized, but the authors did not consider this a pregabalin-related adverse effect.

All dogs had plasma concentrations of at least one drug (phenobarbital or potassium bromide) within the therapeutic range. Nine dogs achieved a final dose of pregabalin of 4 mg/kg, and the other two dogs achieved a final dose of 3 mg/kg. One week after the onset of pregabalin, the through plasma pregabalin concentration ranged from 2 to 11 µg/ml.

Although only four dogs reported in this study achieved seizure control with one or less convulsive episodes a month, seizure frequency was significantly (P = 0.005) reduced in the 11 dogs after the initiation of the pregabalin treatment. The mean number of seizures for each cluster event was significantly (P = 0.02) decreased in the three-month period after the initiation of the pregabalin treatment.

Adverse effects attributable to pregabalin administration consisted of sedation, ataxia, dizziness and weakness. Secondary effects of pregabalin tended to resolve when the oral dose of pregabalin was reduced temporarily from 4 mg/kg to 2 mg/kg.

Although most veterinarians consider a seizure frequency of one seizure a month acceptable control, most owners of epileptic dogs would consider one seizure every three months to be acceptable. It is important to mention that though only four of the dogs in this study achieved seizure control (one seizure a month), seizure frequency was significantly reduced in nine dogs. Therefore, the results of this study support the use of pregabalin as an adjunct to phenobarbital or potassium bromide (Table 1) in epileptic dogs poorly responsive to standard drugs. Adverse effects associated with pregabalin administration are typically mild and similar to those reported after the administration of gabapentin,2 another GABA analogue that is structurally similar to pregabalin.

Table 1

Dr. Lyman is a graduate of The Ohio State University College of Veterinary Medicine. He completed a formal internship at the Animal Medical Center in New York City. Lyman is a co-author of chapters in the 2000 editions of Kirk's Current Veterinary Therapy XIII and Quick Reference to Veterinary Medicine.

Dr. Bichsel completed his residency in neurology at the University of Georgia in 1984. He is a diplomate of the American College of Veterinary Internal Medicine and works at the Animal Emergency and Referral Center in Ft. Pierce, Fla.

REFERENCES

1. Dewey CW, Cerda-Gonzalez S, Levine JM, et al. Pregabalin as an adjunct to phenobarbital, potassium bromide, or a combination of phenobarbital and potassium bromide for treatment of dogs with suspected idiopathic epilepsy. J Am Vet Med Assoc 2009;235(12):1442-1449.

2. Muñana KR. Newer options for medically managing refractory canine epilepsy. Vet Med 2009;104(7):342-347.