The drugs used in the treatment of the various types of epilepsy we have discussed vary according to the seizure type. Some drugs are better for certain seizures than others. It is, however, important to remember that few anticonvulsants are very specific for particular seizures and that there is a choice of drugs for any particular seizure type. The choice may be related to your doctor’s experience, the side effects that he or she might anticipate and the way in which you as an individual tolerate a particular medication. The choice of a single drug is therefore not absolute.
Grand mal seizures: medications used in the treatment of grand mal seizures include carbamazepine, sodium valproate, phenytoin, primidone, phenobarbitone and clonazepam. The order in which the drugs are listed represents some personal bias by the author. Most people would feel that carbamazepine would be effective with the least side effects, but may disagree with the ‘preference’ listing of the rest of the drugs. It is important for patients to realise that the solution to which drug is best for them may not be a black and white issue. Different doctors may have slightly different approaches to a particular problem.
Absences (petit mal): the drug of choice for this condition is ethosuximide. An excellent alternative is sodium valproate, but its possible liver side effects make it a drug of second choice. In children whose absences are particularly resistant to treatment, clonazepam may be helpful.
Temporal lobe epilepsy (complex partial seizures): carba-mazepine is the drug of choice with phenytoin or sodium valproate being acceptable alternatives. Clobazam may be a useful adjunct (additional therapy) in some people with temporal lobe seizures.
Focal seizures: carbamazepine is the drug of choice, followed by phenytoin, sodium valproate or one of the barbiturates.
Reflex epilepsy: drug therapy is not often needed in this condition. Those whose fits are induced by sitting very close to the television should view it from three metres away in a well lit room. In addition, they should not approach the set in order to adjust it or change the channel. If the photosensitivity is induced by sunlight, then polarised sun glasses should be worn. If medication is required, sodium valproate is the drug of choice.
Infantile spasms: the treatment of this condition is difficult and the basis of it little understood. The drugs most commonly used are corticosteroid preparations such as corticotrophin (ACTH) and prednisone. An alternative is a group of drugs, the benzodiazepines, of which the most familiar to the general public would be diazepam (Valium). From this particular group of drugs, nitrazepam and clonazepam may be useful in the management of infantile spasms.
Myoclonic and tonic seizures: these are perhaps the most difficult forms of seizures to treat. The drugs of choice are probably sodium valproate, nitrazepam, clonazepam, and ACTH. If these have failed in children, the use of a ketogenic diet, which will be discussed later, may be considered.
Status epilepticus: as previously mentioned, status epilepticus is a medical emergency. The possibilities for non-professional management of this situation at home are limited. However, in children who recurrently have severe or prolonged seizures, it may be appropriate for a parent to administer rectal diazepam (Valium) to their child. This can be done by drawing up some diazepam into a narrow syringe and inserting it into the child’s rectum (back passage) and injecting the solution. Not all parents wish to do this, but it can be very useful and avoid a lot of trips to hospital.
A further matter worthy of discussion is that of therapeutic drug monitoring (blood level monitoring). Patients with epilepsy will be familiar with the practice of having blood samples taken from time to time to measure the blood levels of their anticonvulsant drugs. When a drug is administered to a person, it accumulates in the body over a few days and eventually reaches a certain level in the blood stream. As far as anticonvulsants are concerned, after taking medication regularly for about a week, the blood concentration will be at what is called ‘steady state’. If the patient continues to take the medication regularly thereafter, while there may be slight ups and downs in the concentration (level) over a 24-hour period, it will eventually remain stable (at a steady state).
Therapeutic drug monitoring determines whether the patient’s blood level is within what is called the ‘therapeutic range’. This is the range of blood concentrations within which the majority of people with epilepsy will have good seizure control with minimal drug side effects. This does not mean that every patient has to be within the therapeutic range. Some patients may be controlled very well with their blood levels below the therapeutic range, while others, if they do not have side effects, may need to be above the therapeutic range. The therapeutic range is just an average level. However, the therapeutic range and blood level monitoring are very useful for the doctor for some anticonvulsants, especially for phenytoin. Blood level measurements may be useful for carbamazepine,
phenobarbitone, primidone and perhaps ethosuximide. They are of little, if any, value for sodium valproate, nitrazepam, clonazepam or clobazam.
When should blood levels be measured? Unfortunately, it has become almost routine to measure the blood levels of anticonvulsants in all epileptic patients, every time they visit their doctor. This is quite unnecessary and has almost replaced the conversation with the doctor which is so essential to those who have epilepsy. Obviously, if a patient has good seizure control and no side effects, there is little need to measure any blood levels. The indications for blood level monitoring include:
Poor seizure control. This may be because the person is not taking his or her medication (non-compliance), is not receiving a sufficient amount of an appropriate medication, or is receiving an inappropriate medication. It may also be because the fits are uncontrollable or that the diagnosis of epilepsy is in fact wrong.
Polytherapy. This describes patients who are receiving more than one drug, usually because their seizures are difficult to control. There may be interactions between the drugs and in that case measuring the blood levels may be of value.
Side effects. If a patient is on only one drug (monotherapy) and has side effects, there may be no need to measure the blood level as it will be obvious what the cause is. It may be sufficient to stop the drug for a day or two to let the blood level decline. On the other hand if a patient is receiving several drugs (polytherapy), it may not be possible to know which drug is causing the problem without measuring the blood levels.
In the very young, the elderly or the handicapped: These groups may handle anticonvulsants differently in the body and may not be able to describe side effects which they are experiencing.
Phenytoin. Phenytoin is broken down in the body by the liver in a rather complicated way which is different to other anticonvulsants. The difficulty with phenytoin is that, contrary to expectation, as the dosage is increased the concentration in the blood stream does not increase proportionally. This means that as the dosage is increased, the blood concentration may suddenly rise quite precipitously and the patient may become intoxicated. For this reason, patients who are receiving phenytoin should have regular blood tests, at least when they are being started on treatment, until they are stabilised on the medication.
There are a number of other indications for blood level monitoring which are still open to debate, but these are uncommonly needed and will not be discussed in detail. As children grow they will need to have their anticonvulsant dosage increased, so occasional blood level tests may be of value.
Absences (petit mal): the drug of choice for this condition is ethosuximide. An excellent alternative is sodium valproate, but its possible liver side effects make it a drug of second choice. In children whose absences are particularly resistant to treatment, clonazepam may be helpful.
Temporal lobe epilepsy (complex partial seizures): carba-mazepine is the drug of choice with phenytoin or sodium valproate being acceptable alternatives. Clobazam may be a useful adjunct (additional therapy) in some people with temporal lobe seizures.
Focal seizures: carbamazepine is the drug of choice, followed by phenytoin, sodium valproate or one of the barbiturates.
Reflex epilepsy: drug therapy is not often needed in this condition. Those whose fits are induced by sitting very close to the television should view it from three metres away in a well lit room. In addition, they should not approach the set in order to adjust it or change the channel. If the photosensitivity is induced by sunlight, then polarised sun glasses should be worn. If medication is required, sodium valproate is the drug of choice.
Infantile spasms: the treatment of this condition is difficult and the basis of it little understood. The drugs most commonly used are corticosteroid preparations such as corticotrophin (ACTH) and prednisone. An alternative is a group of drugs, the benzodiazepines, of which the most familiar to the general public would be diazepam (Valium). From this particular group of drugs, nitrazepam and clonazepam may be useful in the management of infantile spasms.
Myoclonic and tonic seizures: these are perhaps the most difficult forms of seizures to treat. The drugs of choice are probably sodium valproate, nitrazepam, clonazepam, and ACTH. If these have failed in children, the use of a ketogenic diet, which will be discussed later, may be considered.
Status epilepticus: as previously mentioned, status epilepticus is a medical emergency. The possibilities for non-professional management of this situation at home are limited. However, in children who recurrently have severe or prolonged seizures, it may be appropriate for a parent to administer rectal diazepam (Valium) to their child. This can be done by drawing up some diazepam into a narrow syringe and inserting it into the child’s rectum (back passage) and injecting the solution. Not all parents wish to do this, but it can be very useful and avoid a lot of trips to hospital.
A further matter worthy of discussion is that of therapeutic drug monitoring (blood level monitoring). Patients with epilepsy will be familiar with the practice of having blood samples taken from time to time to measure the blood levels of their anticonvulsant drugs. When a drug is administered to a person, it accumulates in the body over a few days and eventually reaches a certain level in the blood stream. As far as anticonvulsants are concerned, after taking medication regularly for about a week, the blood concentration will be at what is called ‘steady state’. If the patient continues to take the medication regularly thereafter, while there may be slight ups and downs in the concentration (level) over a 24-hour period, it will eventually remain stable (at a steady state).
Therapeutic drug monitoring determines whether the patient’s blood level is within what is called the ‘therapeutic range’. This is the range of blood concentrations within which the majority of people with epilepsy will have good seizure control with minimal drug side effects. This does not mean that every patient has to be within the therapeutic range. Some patients may be controlled very well with their blood levels below the therapeutic range, while others, if they do not have side effects, may need to be above the therapeutic range. The therapeutic range is just an average level. However, the therapeutic range and blood level monitoring are very useful for the doctor for some anticonvulsants, especially for phenytoin. Blood level measurements may be useful for carbamazepine,
phenobarbitone, primidone and perhaps ethosuximide. They are of little, if any, value for sodium valproate, nitrazepam, clonazepam or clobazam.
When should blood levels be measured? Unfortunately, it has become almost routine to measure the blood levels of anticonvulsants in all epileptic patients, every time they visit their doctor. This is quite unnecessary and has almost replaced the conversation with the doctor which is so essential to those who have epilepsy. Obviously, if a patient has good seizure control and no side effects, there is little need to measure any blood levels. The indications for blood level monitoring include:
Poor seizure control. This may be because the person is not taking his or her medication (non-compliance), is not receiving a sufficient amount of an appropriate medication, or is receiving an inappropriate medication. It may also be because the fits are uncontrollable or that the diagnosis of epilepsy is in fact wrong.
Polytherapy. This describes patients who are receiving more than one drug, usually because their seizures are difficult to control. There may be interactions between the drugs and in that case measuring the blood levels may be of value.
Side effects. If a patient is on only one drug (monotherapy) and has side effects, there may be no need to measure the blood level as it will be obvious what the cause is. It may be sufficient to stop the drug for a day or two to let the blood level decline. On the other hand if a patient is receiving several drugs (polytherapy), it may not be possible to know which drug is causing the problem without measuring the blood levels.
In the very young, the elderly or the handicapped: These groups may handle anticonvulsants differently in the body and may not be able to describe side effects which they are experiencing.
Phenytoin. Phenytoin is broken down in the body by the liver in a rather complicated way which is different to other anticonvulsants. The difficulty with phenytoin is that, contrary to expectation, as the dosage is increased the concentration in the blood stream does not increase proportionally. This means that as the dosage is increased, the blood concentration may suddenly rise quite precipitously and the patient may become intoxicated. For this reason, patients who are receiving phenytoin should have regular blood tests, at least when they are being started on treatment, until they are stabilised on the medication.
There are a number of other indications for blood level monitoring which are still open to debate, but these are uncommonly needed and will not be discussed in detail. As children grow they will need to have their anticonvulsant dosage increased, so occasional blood level tests may be of value.
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