Canine epilepsy is a challenging clinical problem and once treatment is started it is usually required lifelong. Treatment selection should always be based on a careful comparison of the individual risk-benefit ratio for the different treatment options. Proven efficacy, tolerability and safety are the main criteria for selection of any antiepileptic therapy. Standard therapy includes phenobarbitone and bromide and there is much clinical evidence for their use although phenobarbitone is the only licensed veterinary drug for treating epilepsy. The advantage of a licensed canine product is that the pharmacodynamics of the veterinary formulation will be known in dogs. Generic human preparations of antiepileptic medication may have quite different properties in dogs than in man.

Treatment
Treatment options for epilepsy in man have improved dramatically since the early 1990s with the introduction of nine new generation antiepileptic drugs (AEDs) (felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, vigabatrin and zonisamide). In human medicine, a first line drug for patients with newly diagnosed epilepsy must demonstrate satisfactory efficacy as a monotherapy and few of the new anti-epileptics have achieved this. New generation AEDs are likely to become more important in the management of human epilepsy as experience with their use is gained (Tomson, 2004).

Management & research
To date published studies in dogs have looked primarily at the efficacy and pharmacokinetics of phenobarbitone and potassium bromide and most epileptic dogs are managed effectively with these “standard” anticonvulsant drugs. However, approximately one-third are refractory to appropriate doses of these drugs and further increases in the dosage, in an effort to improve seizure control, can lead to unacceptable side-effects. Clinical trials have also been published investigating the use of felbamate for partial seizures, per rectum diazepam, zonisamide and primidone. Four human drugs that have been used as adjunctive anticonvulsant medications in dogs are felbamate, gabapentin and zonisamide and levetiracetam.

Clinicians at the Animal Health Trust in Newmarket have completed a study into the efficacy of gabapentin as an adjunctive therapy for the management of refractory idiopathic epilepsy in dogs. Five of 11 dogs with refractory idiopathic epilepsy showed a significant reduction in seizure frequency when treated with gabapentin. However, many dogs still had cluster seizure activity on multiple days. Gabapentin was well tolerated - five dogs exhibited mild side effects (ataxia and sedation). This small study indicates that gabapentin may reduce seizure frequency in some dogs with refractory idiopathic epilepsy. A larger study is warranted to further evaluate the potential benefits of gabapentin in epileptic dogs. Like many human drugs gabapentin will be an expensive treatment for dogs.

The use of felbamate 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 (as reported in man). Although sedation is not seen with this drug, excitability ahs been reported at high doses. The cost of treatment with felbamate will also be high. In a study using zonisamide twice daily, in 12 dogs with refractory idiopathic epilepsy, 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. Zonisamide is not available in the UK.

Phenytoin has little place in the management of canine epilepsy due its rapid metabolism in dogs. A slow release formulation is now available but no trials have been published on slow release phenytoin and the presently available form should not be used with phenobarbitone and has erratic gastrointestinal bioavailability It is essential that the use of any new treatment is properly documented to identify potential benefits and adverse effects. The anecdotal reports of success with any treatment must be interpreted with great caution. Benefit to the whole canine population can only be achieved by an evidence-based approach - so that the most efficacious treatments can be identified and made available to all; whilst time is not wasted repeating the mistakes of others with unefficacious treatment. In addition to the information on efficacy, safety and tolerance one of the main advantages of licensed (over non-licensed) veterinary products is the monitoring of  suspected reactions to licensed products by an independent body. This monitoring is an ongoing process with an obligation on license holders to track, investigate and record reactions. This makes it possible to find out whether any suspected reaction has been reported for a particular product.

There are significant risks in the direct translation of results from human medicine to the veterinary field. It is important to study possible therapies in the species in which they are to be used. Contrary to the situation in humans (where gabapentin is excreted unchanged by the kidneys), gabapentin is metabolised by the liver in dogs and this puts this species at risk of hepatotoxicity (although this has not yet been documented). This risk may be increased when gabapentin is administered with phenobarbitone.

There is a clear need for another antiepileptic drug for use in dogs with idiopathic epilepsy which are refractory to the combination of phenobarbitone and bromide. It should be remembered that in human patients conventional treatments are always explored fully, and only if epilepsy is refractory to these treatments are other possibilities explored.

Clinical trials
The Royal Veterinary College, in association with the Animal Health Trust, is running a clinical trial to test the efficacy of Levetiracetam – the most well tolerated anti-epileptic drug in man, (with adverse reactions equivalent to placebo). In man this is a highly effective adjunctive therapy to control seizures refractory to standard treatment.

There are anecdotal reports of the use of adenosine agonists (e.g.vivitonin) in epileptic dogs, however there is no published work on its use in the management of canine seizures.

References

Spinella M (2001) Herbal Medicines and Epilepsy: The Potential for Benefit and Adverse Effects. Epilepsy Behav 2 (6), 524-532 - PubMed -

Tomson T J (2004) Drug selection for the newly diagnosed patient: When is a new generation antiepileptic drug indicated? Neurol 251 (9), 1043-1049 - PubMed -