Treatment

Epileptic seizures are damaging to the brain. The seizure places a great strain on the individual nerve cell, because of greatly increased metabolic processes during the seizure. This brings with it marked changes in the nerve cell's surroundings. The concentration of various substances increases, for example calcium, which has a damaging effect on the nerve cell. The result of a single epileptic seizure is that some nerve cells are lost. This is of great importance, as nerve cells cannot be recreated. Repeated seizures over a number of years will lead to a considerable loss of nerve cells. The same can be seen after status epilepticus. The result is a premature senile decay, so-called dementia, which causes noticeable forgetfulness, memory loss, unstable temperament and increasing lack of judgement and emotional bluntedness. It is therefore vital to get seizures treated and under control as soon as possible.

It is not proved that all types of seizure are as damaging to the human brain. There is unanimity in that convulsive seizures do damage. On the other hand it is less certain how large a roll is played by simple partial seizures without secondary generalization. The damage done by absences is supposedly minimal.

In addition to the influencing intellectual performance, seizures also carry a risk of accidents occurring, depending on where and when they occur. It can for example be a risk of a fall with resulting head injury, or the risk of drowning, if seizures occur while bathing.

There is seldom any good reason to start treatment after a single seizure. At least two seizures need to have occurred for the diagnosis epilepsy to be made. However, if serious changes typical of epilepsy are seen on EEG after only one seizure has occurred, it may be justified to start treatment.

After the second seizure there is usually a cause for treatment. An exception is if a long time has passed since the first seizure. When seizures are very rare it can be questioned if treatment is reasonable. It is a question of weighing the problems the seizures give, against the economic costs and the problem of having to remember to take medicine every day.

The treatment of seizures without convulsions cannot be said to be vital. If simple or complex partial seizures are treated or not will depend on seizure frequency, severity, and the possibility of excluding seizure-provoking factors. Attention should also be paid to conditions of work, the question of the driving license and the family and social situation.

The choice of drug is determined by the:

Effect, control of treatment, side effects and price

It is important to understand that although there are some "basic rules" as to which drug works best against which type of seizure, the individual epilepsy patient often has to "feel his way" forward. This is because there is a difference from person to person in how the drugs work, and what side effects they give.

All drugs have side effects. In the case of single drugs there are noticeable differences in how often they occur, just as the type of side effect is different from drug to drug.

There are two types of side effects to antiepileptic medicine, just as there are to all other drugs. They are acute and chronic side effects.

Skin-rash

The most commonly used antiepileptic drugs give similar acute dose-dependent side effects. Drowsiness, poor memory, difficulty controlling the arms and legs, dizziness, double vision, nausea and headaches can all occur. These side effects disappear when the dose is reduced.

Acute side effects are rarer and less unpleasant in the case of valproate, carbamazepine, oxcarbazepine and vigabatrin compared to many of the other anti-epileptic medicines.

The new medicines used in the treatment of epilepsy are much more expensive than the old drugs. This is because it has generally become very expensive to develop new drugs, also those for the treatment of epilepsy. The Health Authorities in all countries have increased their requirements as to documentation of the effects of any new drug. The requirements of the proof of a new drugs safety to be used on human beings have also been increased.

Even in countries where the patient receives a subsidy towards the cost of medicines, there is still an appreciable difference between the cost of the old and the new drugs.

When we, in spite of this difference, recommend the new drugs, it is in order to avoid the chronic side effects which many of the old medicines have. These side effects are not only unpleasant, they can also result in the user becoming an invalid.

Before starting treatment with a particular medicine, the person should be questioned as to whether he has had that medicine before, and, if so, if he could tolerate it. It is very important to give the doctor exact details of possible allergic reactions to medicines one has taken in the past, so that a new over-sensitive reaction, which could be highly dangerous, can be avoided.

One should be weighed before treatment starts. Weight increase is a side effect of many anti-epileptic medicines. This can be because one eats more (valproate, vigabatrin, tiagabine), or accumulates more water in the body (carbamazepine, oxcarbazepine). Weight loss may be seen in patients treated with topiramate. Weight should therefore be controlled every time the patient comes to out-patient control. If he gains weight during treatment, the medicine content of the blood might fall and there is a risk of seizures. It may be necessary to increase the dose.

Weighing is particularly important in children. This is because their weight changes considerably as they grow. Each time their weight is checked, there is the possibility that their dosage should be altered accordingly.

Treatment starts with a small dose which is gradually increased until the planned dose is reached. This is applies specially to lamotrigine, topiramate, carbamazepine, oxcarbazepine, clonazepam, primidone and ethosuximide, drugs which can give many side effects if the full dose is started straight away. The most usual dose-related side effects can be avoided in this way. The phasing-in of the tablets can often be done with the help of a schedule. Sometimes this must be "made to measure" for the individual patient, in order to avoid side effects.

Difficulties during the phasing-in of the medicine usually mean that it has gone too fast. The body needs more time to get used to the new drug. If lengthening the introductory period removes the problem, the patient can tolerate the medicine. Many patients claim that they cannot "take" a particular medicine. In most cases this only means that a previous treatment was started too abruptly.

In the past epilepsy medicine and other medicines, were given in doses determined by their clinical effect. That is to say, the dose was adjusted according to the result which could be achieved.

Today it has become possible to, measure the concentration of medicine in the blood, which is a considerable improvement. It has been shown that, in the case of epilepsy medicine, there are very large differences between individuals in how fast medicine is broken down.

The result is that if the same dose (in mg/kg) is given to several people, a very different medicine-content of the blood can be measured in each person. It has been shown that there is a very close connection between the amount of medicine in the blood and the its effectiveness. This connection is better than the connection between dose and effect. It is therefore better to measure the medicine content of the blood, instead of just running on the size of the dose.

The reason that the same dose can give such different plasma levels is that we are all individuals, for example when it comes to how fast our livers break down medicine. One cannot know in advance if one belongs to a group which breaks down medicine slowly or fast.

If an epilepsy medicine is given, which has a half-life of 8 hours, it is necessary to dose 3 times a day to achieve a stable concentration in the blood. It is therefore an advantage to have medicine with as long a half-life as possible, so as not to have to take medicine too many times a day.

The half-life of most ant-epileptic drugs is so long that they only need to be taken twice in the course of 24 hours. It is an advantage to take tablets as few times a day as possible. If tablets have to be taken in the middle of the day, at work or school, problems can arise. It is known that treatment is adhered to best if pills only have to be taken once or twice a day. If it is necessary to give medicine more often, the risks of some doses being forgotten are large.

Retarded formulation

In the case of some antiepileptic drugs, for example carbamazepine, which have such a short half-life that the dose would have to be given 3 times a day to achieve a stable blood content, new "retard" formulas have been developed. The tablet's absorption time in the intestine is prolonged. It is then possible to take the tablets less often, and maintain a stable blood concentration.

Some medicines, clonazepam, ethosuximide, and primidone, need to be taken 3 or 4 times a day, although the half-life is long. This is because the single dose must not be too large, as one then would risk getting acute dose-related side effects. These are avoided by dividing the daily dose into many small doses. In this situation it is also recommended to use a dosage dispenser to ensure that the treatment is correctly complied with (see below).

If a medicine gives stomach problems, it is best to take the tablets straight after meals, when the stomach's lining is protected by the food.

Steady state: This means the state where one has achieved a stabile concentration of medicine throughout the day. Although one talks of a "stable" concentration in the blood, there will be small variations through the day. They are however variations on either side of the same centre point.

When treatment is started with a new drug, 5 times the half-life's length must pass before the concentration in the blood is stable. With a drug with a half-life of, for example, 12 hours, the medicine will be stable in the blood after 60 hours. If it is a case of slow phasing in of a dose, 5 times the half-life length must pass, from the time the "full" dosage is given. If one for example takes carbamazepine (half-life about 12 hours), and full dose is first given on day 8, it will take 8 + 2 ½ = 10 ½ days to achieve steady state. There shall, in other words go at least 10 ½ days before one can begin to evaluate how the medicine is working.

If it , for example, turns out that the dose is too low, there must go another 5 half-lives before one can evaluate if the new dose is working, as well as possibly measure the concentration in the blood. It is useless to change the dose of a drug at this point. One must have patience and wait sufficiently long each time in order to evaluate the effect of the changes made.

Therapeutic range or optimal range: By examining many people it has been established what concentration of each type of medicine should be in the blood for it to have the optimal effect and give fewest side effects. This is the "therapeutic range". Its lower boundary is delineated by the concentration the drug should have in order to have an effect, and its upper boundary is the concentration where most people would begin to have side effects. It is important to remember that the "therapeutic range" is only a statistical concept. That is to say, it applies to many, but not all, people with epilepsy.

Milder forms of epilepsy can often be treated with a drug level below the therapeutic range. In some severe cases it can be necessary to increase the dose to a level which lies above the therapeutic range before satisfactory control of seizures is achieved. This is obviously quite acceptable, as long as the person can tolerate such concentrations without getting side effects. Each individual has his own therapeutic range.

Interactions: By this we understand that one drug influences the body's breaking down of another medicine.

There are many examples of epilepsy medicine being influenced by another type of medicine, for example, painkillers.

The result may be that the breaking down of the epilepsy medicine is hampered. This causes an increase in the medicine content of the blood, despite unaltered dosage. The result is often dosage-related side effects.

The other possibility is that the breaking down of the epilepsy medicine is speeded up. This causes the concentration of epilepsy medicine in the blood to fall. The result may be that seizures return, or begin to occur more often.

If medicine is prescribed, which is to be taken at the same time as epilepsy medicine, one should be sure that the doctor is aware which type of medicine one is taking for epilepsy.

Seizure diary

Most people are bad at remembering things, and this is also true of epilepsy patients. In order to keep track of what seizures one has had it is therefore important to keep a seizure diary. It should be brought to every consultation at the out-patient clinic. If the person has more than one kind of seizure, different symbols can be used to indicate the different types. If you cannot remember seizures, a family member, teacher or fellow worker can help you by filling in the diary.

The seizure diary is the only tool the doctor has to "manage" treatment by. It is therefore crucial that you do not have to depend your all to fallible memory to retain this information.

Vomiting

It is important to go to your check ups at the out-patient clinic. Seizure frequency, weight and side effects are controlled. At the same time the medicine content of the blood is tested and other blood tests may be taken to guard against side effects. The frequency of out-patient visits depends on seizure frequency. If new medicine is being introduced, it may be necessary to come every month or every few months, depending on seizure frequency. When there are no seizures there are no grounds to come more often than once or twice a year. Children must be controlled more often, because they grow and put on weight. This can change their need of medicine.

When you are brought into the casualty ward because of seizures or side effects, the concentration of medicine in the blood is checked. You should always carry information giving details about your epilepsy and treatment.

It is best to treat with a single drug, monotherapy, if possible. It used to be believed that using several drugs increased each drug's effect. This has been shown to be incorrect. Treatment with a single drug is in most cases the most effective. Several antiepileptic drugs taken together can increase the side effects of the individual drug. When several drugs are used together it is difficult to decide which one is responsible for the side effects. If the first chosen drug does not stop the seizures, the next choice is tried. At first, the first drug must continue to be given. If the seizures come under control, the first drug can slowly be withdrawn. It is highly likely that drug number two will be sufficient. If the seizures reappear when only drug number two is given, one of the other drugs should be tried in the same way. The overriding rule is to treat with as small an amount of medicine as possible. This method means that only one change of treatment should be carried out at one time. If one at the same time starts giving a new drug and withdrawing an old, and problems arise, there is no way of deciding which process is responsible. It is therefore a golden rule in the treatment of epilepsy only to make one change at a time in treatment. Then it is always possible to establish "cause and effect".

Only when treatment with the different drugs individually has not had sufficient effect should an attempt be made to combine drugs, so-called polytherapy. The people who need treatment with more than one drug are those with severe epilepsy, or those who have several types of seizures. In all, it amounts to about 20% of those with epilepsy.

It is not always an advantage to be seizure free if the person is prevented, by side effects, from leading a normal life. The final results must be carefully weighed in the balance before adding another drug to the list of those being taken. The gain may be so insignificant that the person may be better served without the extra drug. As long as one cannot achieve freedom from seizures without at the same time having to suffer inconvenient side effects, the possibility of surgical epilepsy treatment should be considered.

When you have been seizure free for several years, the question of stopping treatment arises. Experience shows that the course of epilepsy is often such that the illness disappears in the course of time. This has nothing to do with the treatment you have had. That has only served to keep seizures away. It is part of the "natural history" of the illness. In the case of adults, at least five years should have passed without seizures, but in the case of children we will often try to withdraw treatment after two or three years without seizures. You must realize that there is about a 40% risk of seizures reappearing. The risk is greatest if the epilepsy is caused by an organic brain disease, or if it is a case of partial seizures, particularly partial complex seizures, or if it was difficult to bring the seizures under control in the first place. On the other hand the chances of success are better in cases of mild epilepsy in children.

If seizures start again after withdrawal of medicine, it is usually easy to get them fully under control again by giving the same medicine as before.

Some wish to continue treatment, no matter how long they have been free of seizures. They are willing to accept the bother of having to take medicine every day, as well as taking the risk of chronic side effects. Others are eager to try to manage without medication.

It is naturally up to each individual to make this important decision for himself, in consultation with his doctor. If you are afraid of having seizures at work, or if you are dependent on your driving license, you can arrange that the attempt to withdraw medicine takes place during a holiday period.

It is dangerous to experiment by yourself. There is a high risk of status epilepticus, with serious brain damage resulting, if withdrawal does not proceed in the right way. When doctor and patient have agreed to withdraw the medicine, it should be done slowly over weeks or months. Only in the case of serious side effects, such as allergic skin-rash or signs of acute liver damage, should treatment be stopped abruptly. Treatment should then should continue immediately with another quick-working drug.

Before pregnancy

Valproate and carbamazepine are under suspicion as causing spina bifida in the child. If treatment is given with one of these drugs, it is advisable to have an amniotic fluid test which can reveal any malformation in the fetus. An abortion can then be carried out.

When the woman has become pregnant, she should straight away be referred to the maternity unit where the birth is to take place. It is well known that women with epilepsy have a slightly higher risk of complications during delivery than other women, and that their babies are often born prematurely. It is therefore important that the birth takes place in a maternity unit close to the epilepsy clinic.

Control during pregnancy

Medicine content in the child

Breast feeding