Novel anticonvulsant agents for use in refractory epilepsy

Most epileptic dogs are managed effectively with “standard” anticonvulsant drugs i.e. phenobarbitone and bromide. However, approximately one-third are refractory to appropriate doses of these drugs. Increasing the dosage of phenobarbitone and bromide in an effort to improve seizure control can lead to unacceptable side-effects. There are few alternative anticonvulsants to use as additional therapies in refractory canine seizure cases, as most of the available drugs used in people have very short elimination half-lives or are toxic to dogs. The 3 human drugs which have been used as adjunctive anticonvulsant medications are felbamate, gabapentin, zonisamide and pregabalin. Clinicians at the AHT studied the efficacy of Gabapentin as an adjunctive therapy for the management of refractory epilepsy in dogs. The study included 11 dogs with refractory idiopathic epilepsy. Five dogs showed a significant reduction in seizure frequency (ie seizures reduced to less than 50% per week). However, many dogs still exhibited multiple days on which there was cluster seizure activity. Gabapentin was well tolerated - five dogs exhibited mild side effects (ataxia and sedation).

Felbamate has an elimination half-life in dogs of approximately 5-6 hours and requires dosing three times daily. Its use has been documented in 6 dogs which all showed an improved seizure frequency after a median duration of therapy of 9 months; potential side-effects in dogs include haematological abnormalities, keratoconjunctivitis sicca and hepatotoxity.

Zonisamide has an estimated elimination half-life of 15 hours in dogs, and has been administered twice daily in 12 dogs with refractory idiopathic epilepsy. In this study 58% of dogs responded favourably, experiencing a mean reduction in seizures of 81.3%. Five of the twelve (42%) dogs actually had an increased seizure frequency and 50% of the dogs exhibited side-effects which included sedation, ataxia and vomiting.

Pregabalin There is a clear need for another anticonvulsant for use in dogs with idiopathic epilepsy which are refractory to the combination of phenobarbitone and bromide. An ideal adjunct to this combination therapy would be effective in reducing seizure frequency or severity when administered twice daily without such side-effects as sedation or hepatoxicity.

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