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We have had anti-epileptic drugs (AEDs) for over 100 years. The effectiveness of AEDs in totally controlling various types of fit is dependent on many factors such as the person's age, gender, type of epilepsy and whether the person has any other medical conditions. The number of AEDs has increased dramatically over the past 10 years and new drugs have been added to more established ones. The choice of drug is at times difficult and has to be tailored to each person's particular needs.

AEDs are broadly divided into first and second line drugs. This is not due to their relative effectiveness but is historical and relates to the time they were introduced for general use. The first line drugs include phenobarbitone, phenytoin, primidone, carbamazepine, and sodium valproate. These drugs were introduced between the turn of the century and the middle sixties so they have been used for many years and their usefulness and side effects are well known.

Second line drugs are newer ones, which were introduced from the late eighties and have gone through thorough trial programmes before being licensed for use as AEDs. First line drugs were not tested in the way second line drugs were but they have stood the test of time. The second line drugs include (in the order in which they became available); vigabatrin, lamotrigine, gabapentin, topiramate and tiagabine. There are other, less widely used AEDs that are only used in epilepsy that is severe and resistant to treatment, such as clonazepam, clobazam, acetazolamide and ethosuxamide.

Sodium valproate
This is a first line AED that is mainly used to treat primary generalised epilepsy. It is effective and broad spectrum and therefore can also be used to treat partial seizures with and without generalisation. The drug, in the form of tablets or syrup is easy to take and depending on the particular brand, it is taken either once or twice a day. Unwanted reactions (side effects) can include stomach upset, weight gain, tremor, hair loss with re-growth of wavy hair, effects on the menstrual cycle and possible reduction in fertility and an increased risk of polycystic ovaries. There are some general side effects that occur to some extent with all AEDs and information on these is given below.

Carbamazepine
This AED is used as the first line treatment for partial seizures with or without generalisation. It is not effective for primary generalised epilepsy and can actually increase some seizure types. The drug has to be started slowly and increased gradually over a few weeks to avoid some of the side effects, which can include rashes, drowsiness, balance problems, disturbed liver function and double vision. People taking carbamazepine will have regular blood tests to monitor the effect of the drug.

Phenytoin
Phenytoin is a standard AED that was introduced in the 1930s. It is effective for treating tonic clonic seizures but not for primary generalised epilepsy. It remains a very useful drug for some older patients and for those whose epilepsy is caused by a brain injury or tumour. However, it tends to be used less nowadays because of some of the side effects, which can include skin rashes, sedative effects, balance problems and double vision. When used over a long period of time, it can also cause acne, increased facial hair growth, coarsening of facial features, gum enlargement, disturbed liver function and interaction with other drugs which are processed by the liver. People taking phenytoin will have regular blood tests to monitor the effect of the drug.

Barbiturates (phenobarbitone and primidone)
Primidone appears to work by converting to phenobarbitone in the liver. These drugs are broad spectrum AEDs and have been used for most of this century. However, barbiturates have been used less over the past ten years, mainly because of the side effects. In children they can cause hyperactivity syndrome and in adults they can cause loss of concentration and effects on memory and drowsiness, which affects daily activities. Barbiturates are not used as initial drugs in the treatment of epilepsy; they are addictive drugs and because of this, there may be problems with drug withdrawal.

Vigabatrin
This drug, which was introduced in 1989, acts on a certain chemical messenger (neurotransmitter) in the brain called GABA. GABA is thought to suppress the electrical discharges of an epileptic fit and stop it spreading to other parts of the brain. As with all the newer drugs it was first tested in a group of patients whose epilepsy was not well controlled despite the use of multiple AEDs. Vigabatrin is given in twice daily doses and works in partial seizures with and without generalisation. This drug has been shown to be useful in one of the most severe forms of childhood epilepsy known as Lennox-Gastaut syndrome. However, side effects can include aggression, excitation, mental disorders and changes in vision.

Lamotrigine
This broad spectrum AED is used to treat both primary and partial seizure disorders. It needs to be started slowly and increased cautiously over several weeks to avoid skin rashes. The drug is given in twice daily doses and has been shown to be useful on its own (monotherapy) as well as in combination with other AEDs. It produces fewer effects on mental alertness compared to other AEDs. The drug can interact with others, particularly sodium valproate, and its use has to be carefully monitored.

Gabapentin
This AED is used in combination with other drugs for the treatment of epilepsy. The drug has to be used in three divided doses and it may be necessary to take six or more tablets a day. It does not interact with other drugs and can be started fairly quickly. Side effects are those seen in AEDs in general. Gabapentin is not used for the treatment of absence seizures.

Topiramate
Topiramate is another broad spectrum AED that is used to treat both primary and partial seizures. Twice daily dosing is used and it needs to be started slowly to avoid side effects. Drowsiness, confusion, impaired concentration, depression, aggression, kidney stones and loss of weight are possible side effects.

Tiagabine
This recently licensed AED works when added to other drugs in the treatment of partial secondary generalised epilepsy. It has similar side effects to other AEDs.

Other AEDs
There are other currently available drugs that are usually used as second or even third line drugs when major AEDs fail to control epilepsy. These are usually taken in combination with first line drugs and they include clobazam, clonazepam, diazepam, ethosuxamide and acetazolamide. There are also a number of other drugs which are currently being tested for the treatment of epilepsy but which are not yet licensed for use.

General side effects of AEDs
Most people with epilepsy will need to take AEDs for a number of years. Unwanted side effects of AEDs can include tiredness, nausea, poor memory and difficulty with concentration. However, drug side effects vary and can often be avoided with careful dosing and choice of the correct drug for each individual person. In high doses imbalance, double vision, and slurring of speech can occur. Your doctor will discuss possible side effects with you in detail.

It should be emphasised that AEDs are powerful drugs that act on the chemicals of the brain and should be taken according to the directions given to you by your doctor or specialist nurse. If the drugs are stopped suddenly there is a risk of more frequent fits and sometimes, continuous fitting (status epilepticus). As several drugs may be used together for the treatment of epilepsy, the effects of one drug on another (drug interaction) are important. Some anti-depressants and drugs used to treat some forms of mental illness may make the epilepsy worse and this has to be considered before they are used.

When should AEDs be started?
This very important question is not yet fully answered. Some people may have one or two fits in their lives without any apparent cause, while in others the seizure frequency can be much more, up to several times a day. When someone has a single seizure the decision to start AEDs is not straightforward. If there is no clear cause for the fit then AEDs may well be withheld until a second fit occurs. This practice, which is currently considered to be the most acceptable in the UK, is being studied by the Medical Research Council. Where a clear cause for a first fit can be found, then the likelihood of other fits occurring is high and AEDs are usually started straight away. The choice of the specific drug will depend on the type of epilepsy as well as the age and gender of the affected person and any other medication they may be taking.

Withdrawing AEDs
When the epilepsy is well controlled and there have been no seizures for more than three years, the possibility of withdrawing AEDs can be considered. There are certain types of epilepsy such as juvenile onset myoclonic epilepsy where it is not possible to safely withdraw AEDs. Where someone has generalised tonic clonic seizures after the age of 16 years, pre-existing brain damage or physical and learning disabilities, then withdrawal of AEDs is less likely to be successful.

Even if someone has been seizure free for years and has been driving cars, they will have to stop driving for the first six months of withdrawal from AEDs, and if they have a seizure then they will have to be free of fits for a further year before resuming driving. Generally speaking, up to a third of adults whose epilepsy is well controlled will experience fits again after slow withdrawal. Because of this it is important to take into account all the factors about the epilepsy before making a decision to withdraw AEDs.

General AED information
Anti-epileptic drugs should never be stopped suddenly as this could lead to recurrent fits or even status epilepticus, which is a very serious condition. Most
AEDs are taken once or twice daily. After taking AEDs for a long time a certain level builds up in the body. Because of this there is no need to take a double dose if you forget a single dose. It is possible to drink alcohol while taking AEDs as long as it is occasional and in small amounts. Some people may find that the effects of alcohol are heightened by the AED medication.