Epilepsy is a group of diseases that cause repeated fits (seizures). Many animals, including humans, dogs and cats suffer from epilepsy. In dogs, most of the causes are not known. However, epilepsy often runs in families and it is known to be hereditary in some dog breeds. Unfortunately, epilepsy cannot usually be cured, and your pet may need to be on tablets for life. Our aim is to reduce the frequency and/or severity of the fits with the medication. If your pet has been seizure-free for a year then we may consider slowly weaning him/her off the treatment. Unfortunately, your pet may continue to have some seizures, even when treated with the antiepileptic medication.
It is vital that your pet gets his/her medication every day. The medication needs to be given at the same time and at the same interval every day to ensure that the blood levels of the drug remain stable. We need to monitor the blood levels and liver function by doing a blood test every few months. A seizure diary and blood level diary is useful to monitor how well your pet is doing. Pets can often be confused, have abnormal vision and be wobbly (ataxic) after a fit. Occasionally pets can also show some aggressive behaviour just after a fit, so it is important to handle them very gently in this period.
NB: Most fits only last 1-2 minutes. It is a good idea to time the fits so you are sure of the length. It is very helpful to carefully observe the fit. In particular, what were the first signs, was one side of the body affected first, and what sort of movements your pet exhibited, e.g. running movements, shaking, jaw chomping.
Your pet's fit lasts longer than 5 minutes or if your pet seems to have trouble breathing. Most fits that only last a couple of minutes are not emergencies. However prolonged fits (status epilepticus) or several fits close together (cluster seizures) can be life-threatening and may require urgent veterinary treatment at your local practice.
The treatment of choice for epilepsy is pharmacological (by giving medication, such as tablets). The aim of treatment with anti-epileptic drugs is to regain the balance between excitatory and inhibitory signals, so that the epileptic storm does not develop and spread to neighbouring brain areas. The anti-epileptic drug phenobarbitone and potassium bromide do this by enhancing the inhibitory signals in the brain. Treatment of epileptic patients is symptomatic and not curative. This means that the drugs that we use, do not cure the epilepsy but only control the seizures. Based on this, it is clear that epileptic patients usually have to receive antiepileptic drugs (AEDs) on a life-long basis.
Phenobarbitone, one of the first AEDs, still holds its position as a first-line drug for epilepsies. This drug is a relative safe AED with a high efficacy and a long elimination half-life in dogs (42 - 89 hours). It enhances the effect of the inhibitory signals. Phenobarbitone thereby inhibits spreading of seizure activity and makes it less likely that the seizure spreads in all parts of the brain. Around 30% of phenobarbitone is excreted unchanged renally. However, phenobarbitone is mainly metabolized in the liver. The metabolism of phenobarbitone causes a very strong liver enzyme induction. Adverse effects include sleepiness, wobbliness, increase in appetite, increase in drinking, incontinence and hyperactivity. However, in human medicine because of adverse effects such as sleepiness and behavioural problems (depression or hyperactivity) phenobarbitone is now regarded as second-line therapy for humans in industrial countries.
Bromide has been used as an add-on drug in phenobarbitone-resistant canine epilepsy. Most data on bromide in veterinary medicine has been on potassium bromide. Bromide was also proposed as first drug of choice, e.g., in patients with liver problems. The exact mechanism of action is unknown. Excretion of bromide occurs through the kidneys. Bromide has a very long elimination half-life (about 28 days). Sufficient drug dosage will therefore be reached in about two to three months. Bromides have a narrow therapeutic range in humans. In humans, signs of bromide toxicosis include wobbliness, depression, stupor, muscle pain, dermatological signs such as rash and nodular pustular skin lesions, and gastrointestinal signs such as anorexia, vomiting and constipation. However, bromide in dogs normally has much less side effects. In cats it is known to cause in some animals an asthma like syndrome, which can resolve after stopping the bromide treatment.
One of the major side effects of phenobarbitone is liver toxicity. Liver toxicity occurs more frequently if the epileptic dog has phenobarbitone plasma concentrations above 35 µg/ml. This is especially a problem in phenobarbitone-resistant epileptic dogs, because those dogs have high daily doses of phenobarbitone. Another major side effect of chronic phenobarbitone treatment is affecting the blood cell count. Canine epileptic patients having a combination therapy of phenobarbitone and potassium bromide have a higher risk of developing pancreatitis than epileptic dogs with phenobarbitone monotherapy. Furthermore, skin inflammation has been reported in dogs receiving long-term phenobarbitone administration.
Most of the epileptic dogs regain either seizure freedom or a good reduction of seizure frequency. However, about one third of the epileptic dogs remains to have a high seizure frequency and is classified as pharmacoresistant. These animals might have a reduced quality of life. We therefore decided to use well established human anti-epileptic drugs (Levetiracetam and Topiramate) as an additional treatment option.
Other antiepileptic drugs have been tested in dogs. Zonisamide has been used as an add-on drug in phenobarbitone- and potassium bromide-resistant epileptic dogs and reduced seizure frequency succesfully. Also, felbamate has been reported to reduce seizure frequency in phenobarbitone-resistant dogs. However, felbamate and zonisamide are not licensed in the UK and are very expensive. Thus, the treatment with those substances would be difficult in the UK .
Furthermore, other AEDs like carbamazepine, oxcarbazepine, valproic acid, gabapentin, vigabatrin, lamotrigine, phenytoin, and nimodipine are also not applicable in dogs because of their pharmacokinetic properties particularly the elimination half-life, toxicity, adverse effects, and the cost of potential treatment.
Non-pharmacological treatment such as epilepsy surgery, vagal nerve stimulation, and ketogenic diet have been proposed as therapeutic alternatives in the management of canine epilepsy, but still lack either good tolerability and / or efficacy.