
	Historical Introduction How the brain works Types of Seizures Is epilepsy hereditary? Age-linked epilepsy Epilepsy caused by other illnesses Mental complications in connection with epilepsy Epilepsy as a social and psychological handicap Methods of examination The diagnosis epilepsy Treatment Chronic side effects of antiepileptic drugs Acute treatment Prophylactic treatment Surgical treatment Living with epilepsy Testing of new medicine The course of epilepsy Glossary of medical terms

Prophylactic treatment

Lamotrigine(Lamictal)
Levetiracetam (Keppra)
Gabapentin (Neurontin)
Oxcarbazepine (Trileptal, Apydan)
Carbamazepine (Carbamazepine DAK, Nordotol, Tegretol, Temporol, Tardotol, Trimonil Retard)
Valproate (Deprakine, Depakote, Leptilan, Orfiril)
Topiramate (Topamax, Topimax)
Vigabatrin (Sabril, Sabrilex)
Clonazepam (Rivotril)
Clobazam (Frisium)
Ethosuximide (Zarontin, Zarondan)
Phenytoin (Difhydan, Epanutin)
Phenobarbital (Phenobarbitone)
Primidone (Mysoline, Primidone)
Felbamate (Felbatol)

Definition

In giving prophylactic chronic treatment we try to prevent seizures by giving medicine every day. This is a treatment of the symptoms, as the cause of the epilepsy is often not known, and therefore cannot be treated.

Choice of drugs

There are many different drugs available today for the treatment of epilepsy, and many factors determine which one is best in each individual case.

On the following pages the different drugs are described, those we consider to be the best are listed first. Many of these medicines have an equally good antiepileptic effect, but there is a great difference in their chronic side effects, both in type and in frequency.

Lamotrigine(Lamictal)

Effect	In the development of new drugs to treat epilepsy the focus has up to now been on trying to stimulate the inhibitory neuron network in the brain. The basis for this is the belief that epilepsy may be caused by a reduced functioning of these neuron networks. On the other hand, epilepsy could just as well be caused by a too powerful working of the stimulating neuron networks. Within the last few years there have been attempts made to produce drugs which would restrain the stimulating neuron networks. lamotrigine is one of these drugs.
Application	Lamotrigine is most effective in the treatment of generalized seizures, absences and generalized convulsions. It has less effect against partial seizures. It belongs to the weaker antiepileptic drugs.
Conversion in the body	Half-life Lamotrigine is broken down slowly in the body, with a half-life of about 24 hours.
Dosage	Phasing in of dose Lamotrigine can be taken once or twice a day. A slow introduction of the drug is of benefit to lessen the risk of allergic skin rash, caused by lamotrigine. If rash occurs the patient may be desensitized when the skin has normalized, by slow increase of the dose using tablets of 5 mg each. 80% of the patients will then tolerate the drug without rash.
Concentration in the blood	Therapeutic range The blood content of lamotrigine can easily be determined. The therapeutic range has not yet been determined.
Side effects	An important feature of lamotrigine appears to be it's few side effects. The most common are rash and headache. Rash is seen in only about 10%, mainly in children. The headache is reversible and lasts about a week. It should not be treated by paracetamole (Panodil, Pinex, Kodipar), as this compound lowers the plasma level of lamotrigine.
Interaction with other drugs	Simultaneous treatment with valproate increases the half-life of lamotrigine considerably. If treatment is given with these two drugs at the same time, it is often necessary to reduce the dose of lamotrigine. Paracetamole inhibits the metabolism of lamotrigine.

Levetiracetam (Keppra)

Effect	Levetiracetam is a potent antiepileptic drug with few and rare side effects. The mechanism of action is unknown. It may bind to specific receptors in the brain.
Application	It is used in the treatment of simple and complex partial seizures with and without generalization. It is also effective against absences, myoclonic jerks and primary generalized seizures.
Conversion in the body	Levetiracetam is not metabolized. It is excreted unchanged in the urine. Half-life is 6-8 hours, longer in elderly people.
Dosage	It may be started with full dose, 1500 mg twice a day, however it is often an advantage to start lower.
Concentration in the blood	Therapeutic range The blood content of levetiracetam can easily be determined. The therapeutic range has not yet been determined.
Side effects	About 10% may have somnolence, and asthenia. Dizziness, gastro-intestinal symptoms, anorexia, headache, amnesia, ataxia, depression, aggressivity, nervousness, insomnia, tremor, vertigo, diplopia and exanthema are rare side effects.
Interaction with other drugs	As levetiracetam is not metabolized in the liver interaction with other drugs metabolized here cannot be expected.

Gabapentin (Neurontin)

Effect	Gabapentin is chemically related to the neurotransmitter GABA but its mechanism of action is unknown.
Application	Gabapentin is a weak antiepileptic drug which is used to treat postinfarction epilepsy. It has no interactions with other drugs which makes it advantageous in the treatment of elderly people who often take several drugs. It is also used as adjunctive therapy with standard antiepileptic drugs in patients who have not achieved adequate seizure control with these agents alone or in combination. It is effective against simple and complex partial seizures and secondarily generalized tonic-clonic seizures.
Conversion in the body	Half-life Gabapentin is not metabolized. It is only eliminated by the kidneys. Half-life is 5-7 hours.
Dosage	Phasing in of dose Titration to an effective dose can be accomplished in three days. It is administered three times daily.
Concentration in the blood	Therapeutic range The blood content of gabapentin can easily be determined. The therapeutic range has not been determined.
Side effects	Gabapentin appears to have few side effects. The most common are somnolence, an uncertain gait, dizziness, fatigue, nausea or vomiting.
Interaction with other drugs	There does not seem to be any interactions.

Oxcarbazepine (Trileptal, Apydan)

Application	Oxcarbazepine is a strong antiepileptic drug which is chemically in the same family as carbamazepine. It is used in treating the same seizure types, and has been shown to have as good an effect as carbamazepine.
Conversion in the body	Although the drugs resemble each other, oxcarbazepine is broken down in a different way to carbamazepine. Because of this some of the waste products produced when carbamazepine is broken down are avoided. This is perhaps why oxcarbazepine has fewer side effects than carbamazepine. Another advantage is that oxcarbazepine does not stimulate the liver as carbamazepine does. Enzyme induction Finally, it has proved that, although the two drugs resemble each other closely chemically, 75% of the people who get skin rash under treatment with carbamazepine will be able to change to oxcarbazepine without getting a rash once again. "Steady state" is achieved after 3 -4 days treatment at the full dose.
Dosage	Phasing in of the dose The dose of oxcarbazepine is about 1.5 times the dose of carbamazepine. It is important that the phasing in of the dose takes place slowly in order to avoid acute side effects. Half-life Oxcarbazepine has a half-life of about 8-10 hours. The dose is therefore normally given 2-3 times a day to achieve a stable concentration in the blood. There is no "retarded" formula for oxcarbazepine.
Concentration in the blood	Therapeutic range The level of oxcarbazepine in the blood can be measured, but we have very little knowledge as to within which levels it is most effective.
Side effects	Side effects are the same as for carbamazepine, but occur more rarely, with the exception of accumulation of water in the body, with disturbances in the body's salt balance, which occurs more frequently.
Interaction with other drugs	As oxcarbazepine has only a little effect on the liver's enzymes, there are seldom problems, even when several anti epileptic drugs are being used together. Oxcarbazepine is not, for example affected by dextropropoxyphene (Abalgin, Doloxene) or by erythromycin (Abbotticin, Ery-Maxin, Escumycin, Hexabocin). Contraceptive pill failure Unfortunately oxcarbazepine can cause failure of the contraceptive pill, although the drug generally does not stimulate the liver.

Carbamazepine (Carbamazepine DAK, Nordotol, Tegretol, Temporol, Tardotol, Trimonil Retard)

Application	Carbamazepine is used in treating generalized convulsive seizures and simple and complex partial seizures.
Conversion in the body	Over the first three weeks of treatment the drug is broken down faster and faster, because carbamazepine stimulates the liver. Although the carbamazepine content of the blood will normally be stable after 3-4 days treatment at full dose, it may be necessary to adjust the dose in the first weeks to prevent the carbamazepine level in the blood from falling. After this the treatment is easily controlled.
Dosage	Half-life Carbamazepine is broken down quickly in the body. The half-life is about 8 -12 hours. The dose must be taken 3 -4 times a day to keep a stable concentration in the blood round the clock. "Retarded" formulation The development of the so-called "retarded" formula, by which the length of time it takes to absorb the drug into the bloodstream has been artificially prolonged, has enabled the dose-frequency to be reduced to 1-2 times a day. In addition it has been shown that the "retarded" formula gives fewer side effects than the normal tablets did. This is because the blood concentrations are more stable through the day than with normal tablets. "Retarded" tablets should therefore always be used. Phasing-in When treatment begins, it is important to phase the drug in slowly, over 10 days or so, to avoid acute side effects. If the full dose is given at the start, most people would experience side effects, especially dizziness, and come to believe that they could not tolerate the drug.
Blood concentration	Therapeutic range The content of carbamazepine in the blood can be measured, and we now know within which area the drug should lie in order to achieve a good effect, and avoid side effects.
Side effects	Acute side effects If the drug is phased in too fast, or if the concentration in the blood is too high, typical side effects will occur, such as double vision, uncertain gait, dizziness and drowsiness. In about 5-10% a rash may be seen, often in the first weeks of treatment. This means that another treatment must be used. Very rarely the liver may be affected and anemia may occur. These side effects mean that the treatment must be adjusted. Some people may have an accumulation of water in the body, which can give weight gain and disturbances in the body's salt balance. These patients should also change to another drug, if it becomes pronounced. In old people in particular, disturbances in the heart rhythm may be seen. Chronic side effects If treatment is regularly controlled, carbamazepine has very little effect on the nervous system, in the form of tiredness, lethargy or reduced concentration. Most people can function as well as they did before treatment was started. As carbamazepine as well as giving relatively few side effects, also has outstanding antiepileptic properties, it is one of the best drugs for the treatment of epilepsy.
Interaction with other drugs	Carbamazepine causes other antiepileptic drugs to be broken down faster than normally is the case. This is because it stimulates the liver. Sometimes this can lead to a very large dose of the other antiepileptic drug being taken, in order to achieve a satisfactory level in the blood. The pain-killing preparation, dextropropoxyphene (Abalgin, Dextropropoxiphen DAK, Doloxene) and the preparation erythromycin (Abbotticin, Ery-Maxin, Escumycin, Hexabocin) which is used to treat infections, block the breaking down of carbamazepine. This leads to the concentration of carbamazepine rising, despite an unchanged dose. This can lead to poisoning. Other types of pain killers should be recommended. Failure of the contraceptive pill has also been described. This is because carbamazepine speeds up the break down of the contraceptive pill's hormones.

Valproate (Deprakine, Depakote, Leptilan, Orfiril)

Application	Valproate works well on many different types of epilepsy, especially generalized idiopathic epilepsy such as pyknoleptic petit mal, Rolandic epilepsy, juvenile myoclonic epilepsy and generalized convulsive seizures. In cases of severe epilepsy in children, for example myoclonic astatic epilepsy, an improvement can be seen after treatment with valproate. The drug can also be used in the treatment of partial seizures. Valproate is effective in preventing febrile convulsions. In the case of so-called photosensitive epilepsy, where epileptic changes are seen on EEG when a flickering light is shown during the EEG recording, valproate is the most effective medicine. Valproate is also one the best drugs for treating pyknoleptic petit mal. Ethosuximide is only effective against absences, whereas valproate also protects against convulsive seizures which about half of the children otherwise would develop.
Conversion in the body	Half-life Valproate is absorbed and broken down quickly. This leads to large fluctuations in the concentration of valproate in the blood over 24 hours. Even so, the drug need only be given once a day to maintain a good effect. The reason for this is not known. "Retarded" formula As is usually the case, a "retarded" formula should be used when available.
Dosage	Treatment can be started with the full dose, without phasing in of the medicine. A stable blood concentration, steady state, can be measured after 2-3 days.
Concentration in the blood	Therapeutic range The therapeutic range of valproate is well-defined (350-700 μmol/l).
Side effects	Stomach pains Stomach pains and dyspepsia were in the past common side effects of valproate. After the introduction of coated pills, which first dissolve in the intestine, these problems have virtually disappeared. The most common side effects of valproate are weight gain, hair loss and trembling of the hands. Weight gain About 60% of those treated with valproate experience problems with their weight. The only way to tackle the problem is to eat less. A dietician can be called in to help advise on diet, if necessary. Shaking of the hands depends on the dose size, and lessens when the dose is reduced. If that does not help, the shaking can be removed by treating with propranolol (Inderal, Frekven, Propranolol DAK). Some women find that menstruation stops for a time, but it always starts again. Hair loss Hair loss is sometimes seen during treatment with valproate. It is very rarely noticeable enough to give problems. Treatment with vitamin B can be tried. Liver damage Liver damage is a rare but serious side effect. It is caused by an allergic reaction. This is most often seen in brain damaged small children with severe epilepsy, and always starts within the first six months of commencement of treatment. After it has become a habit of doctors to warn of the symptoms, when treatment with valproate starts, it has become possible to stop treatment in time in the very few cases where this occurs. The symptoms are lethargy, nausea, vomiting, stomach pains, diarrhea and sometimes jaundice. If these symptoms are seen, the doctor should be consulted immediately. In some persons being treated with valproate, a fall in the number of blood platelets is seen, but this only rarely leads to bleeding. Spina bifida Valproate is suspected of giving malformations of the spinal cord, spina bifida, in children born of mothers who are being treated with the drug. The Danish Medical Health Board has issued guide lines for using valproate, because of this suspicion. Pancreatitis Pancreatitis is another rare side effect which has occasionally been observed in children. The symptoms are sudden strong stomach pains. As is also the case with carbamazepine, oxcarbazepine and vigabatrin, valproate does not lead to noticeable lethargy. Tests have shown that the ability to concentrate, reaction time and attentiveness are virtually unchanged during treatment with the drug. Valproate, lamotrigine, levetiracetam, carbamazepine, and oxcarbazepine are therefore the preferred drugs in modern epilepsy treatment.
Interaction with other drugs	Enzyme induction Valproate does not stimulate the liver. Failure of the contraceptive pill is therefore not a problem. Valproate does affect the breaking down of phenobarbital and lamotrigine. This can give a large increase of the concentration of these drugs in the blood, if treatment is being given with valproate and these drugs. There is a risk of poisoning, if a person who is taking lamotrigine and phenobarbital starts treatment with valproate. If treatment with valproate is started when the person is already taking phenytoin, the concentration of phenytoin in the blood will fall.

Topiramate (Topamax, Topimax)

Application	It is a very effective drug in the treatment of simple and complex partial seizures with and without generalization. It is also effective against myoclonic jerks.
Conversion in the body	Topiramate is partly metabolized in the liver, partly excreted unchanged in the urine. The half-life is 20-30 hours. Nevertheless it is most often administered twice a day. When it administered together with inducing drugs the half-life falls to 15 hours.
Dosage	Topiramate must be phased in slowly, starting with 25 mg a day for a week to 14 days and increasing the dose by 25 mg every 14 days until full dose. The drug is to some extent excreted in an unchanged form via the kidneys. In the case of elderly people, who perhaps have a reduced kidney function, a smaller dose should be given to avoid side effects.
Concentration in the blood	Therapeutic range The concentration of topiramate in the blood can be measured. Therapeutic range is 6-30 μmol/l.
Side effects	Topiramate has many side effects, such as dizziness, fatigue, ataxia, paraestesia, confusion, abnormal thinking, agitation, amnesia, aphasia, depression, diplopia, nausea, anorexia, weight loss and kidney stones.
Interaction with other drugs	All the inducing drugs will accelerate the metabolism of topiramate. Topiramate will only accelerate the metabolism of the pill.

Vigabatrin (Sabril, Sabrilex)

Application	In contrast to all other antiepileptic medicines, vigabatrin works better against partial than against general seizures. Vigabatrin is therefore used for treating simple and complex partial seizures with or without secondary generalization. Vigabatrin is also effective in the treatment of children with epilepsy. Current studies show vigabatrin to be specially good in the treatment of infantile spasms, which have otherwise been difficult to treat. The drug can increase the frequency of absences and can provoke myoclonic seizures.
Conversion in the body	Half-life Vigabatrin's half-life is short, only 5-7 hours. Because of the drug's special mechanism, which destroys the enzyme in the brain which breaks down GABA, the length of the half-life has no practical relevance to how often vigabatrin should be taken. The elderly The drug is excreted in an unchanged form via the kidneys. In the case of elderly people, who perhaps have a reduced kidney function, a smaller dose should be given to avoid side effects.
Dosage	Phasing in of the dose Treatment with vigabatrin can be started at the full dose. The medicine is expensive. Treatment is therefore often started with a small dose and slowly increase it, to find how little a dose the individual can "manage" with. Only one dose a day is needed. In many cases twice a day is preferable, because of the number of tablets involved.
Concentration in the blood	Therapeutic range The concentration of vigabatrin in the blood can be measured. Because of it's special effect, however, this has proved to be unnecessary. There is no connection between the concentration in the blood, and the effect the drug has.
Side effects	Vigabatrin has proved to have particularly few but dangerous side effects. Tiredness can be seen with high dosage. A small weight gain can sometimes be seen, but this seldom gives problems. In adults and children whose epilepsy is caused by brain damage, increased restlessness and anxiety can sometimes be seen. Sometimes this problem can be eliminated by reduction of the dose. In rare cases it may be necessary to break off treatment. Very occasional cases of depression or psychosis have been reported. The most dangerous side effect is constriction of the visual field which may be seen in up to 30% of the patients. In many it seems to be an irreversible side effect. The use of this drug is therefore now restricted to very severe types of epilepsy! Micro vacuoles in the brain In some species of animals used in research treatment with vigabatrin led to the development of drop-shaped liquid filled blisters in the brain, the so-called micro vacuoles. Such changes have never been observed in humans, even after lengthy treatment with the drug. Measurement of powers of concentration, reaction time and tiring before and after treatment with vigabatrin shows that the drug has nearly no influence on these functions.
Interaction with other drugs	Enzyme induction Vigabatrin does not stimulate the liver. It therefore does not cause the contraceptive pill to fail. When vigabatrin and phenytoin are given at the same time the concentration of phenytoin in the blood falls.

Clonazepam (Rivotril)

Application	Clonazepam has an effect on all types of seizures and can be used for acute seizure treatment.
Conversion in the body	Clonazepam is broken down very slowly. Half-life The half-life is 20-50 hours.
Dosage	Phasing in of the dose To avoid acute side effects the dose should be slowly introduced over 2-3 weeks. Despite the long half-life, 3 to 4 doses a day are often given to avoid side effects after a single dose.
Concentration in the blood	Therapeutic range Clonazepam can be measured in the blood. This is unnecessary, as there is no apparent connection between the concentration in the blood, and the effect, or side effects. The dose size should therefore relate to its effect.
Side effects	The most common side effects are lethargy, unsteady gait, limp muscles, slurred speech and dizziness. Mental changes such as restlessness, irritability, aggression and bad temper verging on depression, can be seen in both adults and children. It is a great advantage if clonazepam is given alone. Fewer side effects are then seen. Tolerance development The effectiveness of clonazepam unfortunately "tails off" in some people after about 6 to 12 months treatment, the so-called "tolerance development".

Clobazam (Frisium)

Application	Clobazam is very similar to clonazepam. It is also effective against all seizure types.
Conversion in the body	Half-life Clobazam has a long half-life of about 20 hours.
Dosage	Phasing in of the dose Because of the risk of side effects, the dose should be phased in slowly. A small dose is often sufficient. It is only necessary to take one dose a day. Steady state is achieved after 5 days treatment at the full dose.
Concentration in the blood	Therapeutic range clobazam can be measured in the blood. Just as in the case of clonazepam, there is no connection between concentration in the blood and effectiveness of the drug.
Side effects	These are the same as in the case of clonazepam. They are much less pronounced. Unfortunately tolerance development is very common.

Ethosuximide (Zarontin, Zarondan)

Application	Ethosuximide is used in the treatment of pyknoleptic petit mal and myoclonic-astatic epilepsy. It has no effect on generalized convulsive seizures. Neither does ethosuximide prevent the development of convulsive seizures. It is therefore better to treat with valproate.
Conversion in the body	Half-life Ethosuximide is broken down slowly. The half-life is about 30 hours in children, and about 60 hours in adults.
Dosage	Ethosuximide should be given 2 or 3 times a day to avoid side effects from a single dose. In order to avoid stomach pains, the capsules should be taken at mealtime. Phasing in of the dosage Phasing in of the dosage is necessary.
Concentration in the blood	Therapeutic range The blood concentration of ethosuximide can be measured. It is routinely used and is stable (steady state) after about one week's treatment with the full dose.
Side effects	Ethosuximide can irritate the lining of the stomach. If the blood concentration is too high, tiredness, headache and symptoms which resemble sea-sickness can occur. There are also rare side effects such as rash or severe anemia.

Phenytoin (Difhydan, Epanutin)

Application	Phenytoin is used for the treatment of generalized convulsive seizures, simple or complex partial seizures, but has no effect on absences. It is also used in acute seizure treatment.
Conversion in the body	Phenytoin is broken down in the liver, as most drugs are.
Conversion in the liver	The speed at which drugs are broken down usually depends on their concentration in the blood. This makes it easy to adjust the treatment. The changes which occur in the concentration of the drug when the dose is increased or decreased can be predicted. This is more complicated in the case of phenytoin, as an increased concentration leads to "saturation" of the breaking down process in the liver. It simply cannot "handle" any more. This means that even a small increase in dose can lead to unforeseeable changes in the blood. Treatment with phenytoin is therefore difficult to control. It can lead to seizures, if the blood content is too low, or seizures and symptoms of intoxication if the concentration is too high.
Dosage	Half-life The half-life of phenytoin is long. It is therefore sufficient to give a dose 1-2 times a day to achieve a stable concentration in the blood round the clock. There is no need for the dose to be introduced gradually.
Concentration in the blood	Therapeutic range The blood-content of phenytoin should be regularly measured, as the treatment is difficult to control. The therapeutic range is well-known. The blood-content is stable after about 10 days treatment (steady state).
Side effects	Acute side effects The most common side effects are double vision, dizziness and an uncertain gait, which are seen when the blood concentration gets too high. In some cases confusion and involuntary twisting movements of the body, arms and legs are seen. Growth of gums Even when treatment is well-regulated problems often arise with the gums, which can become thickened. Thorough tooth brushing can limit this, but sometimes surgery may be necessary to remove the excess gums. Women and children may have a great increase of body hair. A coarsening of the features may result after many years' treatment. Phenytoin influences many of the body's hormonal systems and the natural defense mechanisms (the immunological system). It reduces the body's defense against infection. Respiratory infections are more common. The excessive growth of the gums is, in fact, a response to chronic gum infection. An allergic reaction is sometimes seen in the form of a rash. Then treatment must be changed to another preparation. Chronic side effects Prolonged treatment with phenytoin may reduce the powers of concentration and lessen physical and mental ability. The person cannot manage to function as well as before, he is tired and goes to bed early. Interest in the world around him diminishes, and hobbies and interests are dropped. This development happens slowly, often without the person being aware of it. Only when phenytoin is withdrawn, and replaced with another drug which does not give these chronic side effects, can the person discover what it is like to live a normal life again. Although the antiepileptic properties of phenytoin are excellent, these side effects mean that it should be used as little as possible.
Interaction with other drugs	Enzyme induction Phenytoin stimulates the liver and can thereby cause a speeding-up of the break-down of other antiepileptic drugs, for example lamotrigine, topiramate, carbamazepine and valproate. Failure of the contraceptive pill has also been described. The concentration of phenytoin in the blood falls when it is given together with valproate or vigabatrin. Disulfiram (Antabuse) Dextropropoxyphene (Abalgin, Doloxene) and sulphur preparations hamper the breaking-down of phenytoin and can cause symptoms of intoxication.

Phenobarbital (Phenobarbitone)

Application	Phenobarbital is effective in treating generalized convulsive seizures and simple partial seizures. It has no effect on complex partial seizures and absences. Phenobarbital can be used as a preventative treatment for febrile convulsions. It can also be used for acute seizure treatment, but takes up to one hour to work, if injected into a muscle.
Conversion in the body	Half-life Phenobarbital is broken down very slowly. This can lead to the risk of it accumulating in the body during long term treatment.
Dosage	Phasing in of the dose One dose a day is sufficient to keep the blood concentration steady. A phased introduction of the dose is not necessary.
Concentration in the blood	Therapeutic range The therapeutic range is known. It takes about three weeks from the start of treatment for the concentration in the blood to become stable (steady state).
Side effects	The most common side effects are tiredness and lethargy., which can occur even at low blood concentrations. The opposite is often seen in children, with restlessness and irritability. These side effects are so common and create such problems, that despite the drug's excellent properties, it should be used as little as possible.
Interaction with other drugs	Phenobarbital is a powerful stimulant of the liver and can therefore cause a speeding up of the break-down of other antiepileptic drugs. Failure of the contraceptive pill is most common during phenobarbital treatment.

Primidone (Mysoline, Primidone)

Application	Primidone is used to treat generalized convulsive seizures and simple and complex partial seizures. It is not effective against absences.
Conversion in the body	Primidone is broken down in the body into phenobarbital and another metabolite, PEMA, which also has an antiepileptic effect. We are not yet sure how large a role PEMA plays, in relation to that played by phenobarbital.
Dosage	Phasing-in of the dose The dose has to be phased in slowly to avoid side effects. The dose is usually given 2-3 times a day to avoid that the single dose be too large.
Concentration in the blood	Therapeutic range Both the concentration of primidone and PEMA in the blood can be measured. Normally only the concentration of phenobarbital is measured.
Side effects	The same as phenobarbital.
Interaction with other drug	The same as phenobarbital.

Felbamate (Felbatol)

Effect	Its mechanism of action may have something to do with a decrease in excitatory neurotransmitters. It possess some protective activity against damage in the brain caused by restricted blood and oxygen supply.
Application	Felbamate is used very little today because of its dangerous side effects! It is mainly used as adjunctive therapy with standard antiepileptic drugs in patients who have not achieved adequate seizure control with these agents alone or in combination. It is effective against simple and complex partial seizures and secondarily generalized tonic-clonic seizures. Seizures associated with the Lennox-Gastaut syndrome in children and adults are also suppressed.
Conversion in the body	Half-life Felbamate is metabolized in the liver. Half-life is 13-23 hours.
Dosage	Phasing in of dose Titration to an effective dose is started by 1200 mg a day and increased to 3600 mg a day if necessary. It is administered three to four times daily.
Concentration in the blood	Therapeutic range The blood content of felbamate can easily be determined. The therapeutic range has not yet been defined.
Side effects	The most common side effects are nausea, vomiting, anorexia, headache, somnolence, double vision, dizziness and sleep disturbances. Aplastic anemia is the most dangerous of its side effects. Aplastic anemia and hepatic failure may not be reversible even if detected early!
Interaction with other drugs	Plasma concentrations of felbamate are increased during coadministration with valproate and decreased with phenytoin and carbamazepine. Plasma concentrations of phenytoin and valproate are increased during simultaneous treatment with felbamate, while those of carbamazepine are decreased and those of the epoxide metabolite of carbamazepine are increased.

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