Treatment of epilepsy

Can you cure epilepsy?
Epilepsy is unfortunately a condition that the animal is born with and as such cannot be cured. Treatment of epilepsy aims at 'controlling' the seizures. While anti-epileptic drug will make some fortunate animal seizure-free, successful treatment more often implies reducing the frequency and severity of the seizures with acceptable side effects.

It is therefore important to understand that the animal will still seizure despite being on treatment. Unfortunately seizure 'control' may not be obtained in up to one third of animal despite adequate therapy.

When to start treatment?
There are two schools of thought. Many dogs will have a single seizure episode in their lives, therefore it may not be feasible to treat every dog that seizures. The first school of thought advises treatment of seizures as soon as a dog is diagnosed as having recurrent seizures (i.e. after the second seizure episode). Experimental evidence and a single study in dogs suggest that early treatment offers better long-term control of the seizures as compared to animals that are allowed to have numerous seizures prior to the onset of treatment.

The second school requires balancing the benefits gained from the introduction of anti-epileptic therapy with the adverse effects caused by the medication and the demands on the owner.

Although largely arbitrary, the following would be a reasonable guide to starting treatment:

• Where more than one seizure occurs per month and/or the owners object to their frequency
• If the animal has a very severe seizure or a cluster of seizures, irrespective of the frequency of the seizures or seizure cluster
• The seizures increase in frequency or severity
• An underlying brain disease has been identified as the cause of the seizures

What are the drugs used for treatment of epilepsy?
Many drugs used in human with epilepsy are either toxic in companion animal or are eliminated too quickly by the body to allow good 'control' of seizure. The first line treatment in dogs is phenobarbitone (Phenobarbitone?, Epiphen?) or bromide (Potassium bromide syrup?, Epilease capsule?, Genitrix?) and phenobarbitone, diazepam (Valium?) or gabapentin in cats.

Phenobarbitone is often the preferred first choice as it takes quicker effect (within 2 weeks) than bromide (3 to 6 months). Bromide can be used as first choice in animal with pre-existing liver disease or animal with very low seizure frequency. Diazepam is not suitable for maintenance treatment of epilepsy in dogs as the duration of effect is too short.

Why regular blood tests are important to monitor the treatment?
More than any other drug, the concentration of anti-epileptic drug in the blood is more important to consider than the quantity of tablet given. This concentration determines not only the good effect (also known as therapeutic effects) but also the toxic and inefficient effects. Blood concentrations of phenobarbitone and bromide should be determined to ensure that they are within a certain range of concentration known as the therapeutic range.

Failure to be within this range (concentration too low or too high), the quantity of tablet should be adapted and the concentration re-check a few weeks later. Response to treatment is extremely variable between animals. Some will need to be on the low end of the therapeutic range while others will need to be at the top end to experience therapeutic effect. This means that checking the concentrations are within the therapeutic range is not enough and consideration must be given to what effects (beneficial or undesirable) it has on the animal.

Compared to bromide, the concentration of phenobarbitone tends to drop with time in dogs (more or less quickly depending on the dog) if the quantity of tablet is kept unchanged. This means that the quantity of tablet will likely need to be increase to keep the blood concentration at the same level. Again this does not imply the animal will more likely suffer side effect as the inefficient, therapeutic and toxic effect are related to the quantity of drug in the blood and not the quantity of tablet given.

When to check the anti-epileptic blood concentration?
Determination of the blood concentration of phenobarbitone is indicated:

• 2 weeks after starting treatment or changing the dosage
• When the seizure frequency seems to increase
• Every 3 to 6 months to verify that blood concentration do not drift out of the intended range
• When undesirable drug-related side effects are suspected
• Determination of the blood concentration of bromide is indicated:
• 3 months after starting treatment or changing the dosage
• When undesirable drug-related side effects are suspected

What are the side effects of anti-epileptic drug?
Therapy for epileptic seizures may have side effects that in rare occasion can be worse than the seizures themselves. Mild side effects are common when first starting treatment (or increasing the dose) with phenobarbitone or bromide and include increase thirst and appetite, more frequent urination, mild sedation and mild wobbliness in the back legs.

Phenobarbitone can have in very rare occasions more serious side effects such as liver toxicity and blood abnormality (low red blood cells, low platelets and low white blood cell count). It is however important to be aware of two points regarding side-effects: (1) dog on phenobarbitone will frequently show some abnormal liver and hormonal parameters without significance for the animal's health and (2) chronic liver toxicity is mainly observed in dog for which the blood level of phenobarbitone is above the recommended range.

Complete blood profiles (liver function test and haematology) are recommended on a six months basis to monitor to such potential side effects. Bromide is a much safer drug by its nature (form of salt) despite still causing increased thirst and appetite. It is absorbed, distributed within the body and pied without interfering with the liver. Its use as only second choice is mainly justified by the long time it takes to reach efficient blood level (around 3 to 6 months).

What are the options if the animal is not responding anymore to anti-epileptic drug?
Many causes can explain why the animal is not responding to treatment: incorrect diagnosis (causes of epileptic seizures other than epilepsy), inadequate choice of anti-epileptic drug for the species treated (e.g. diazepam in dog), inadequate dosage of medication, animal becoming 'resistant' to the therapeutic effect of the drug (also known as becoming refractory).

An animal having been diagnosed with epilepsy is defined as refractory to anti-epileptic treatment when its quality of life is compromised by frequent and/or severe seizures despite appropriate choice and blood concentration of drug.

The first choice drug for use in refractory epilepsy is bromide in dogs, used in conjunction with phenobarbitone. Some dogs may need to be started on a loading dose (five times the usual daily dose per day for five days) to rapidly get the blood levels within the therapeutic range.

If the dog is already on phenobarbitone and bromide, gabapentin and levetiracetam are two newer human anti-epileptic drugs that can be added to the treatment. Rectal diazepam can be used at home in dogs with tendency of severe cluster seizures to reduce the total number of seizure events during a cluster.

Can you take the animal off anti-epileptic drug in the long-term?
It is important not to alter or stop the treatment without veterinary advice. Epilepsy being a condition that cannot be cured, it is very likely that the animal will have to stay on treatment for the rest of its life. Dosage reduction should only be considered if the animal remains seizure-free for at least a good year and should be very gradual over many months to prevent precipitating seizure.

If you are concerned about the health of your pet you should contact your veterinary surgeon.