Antiepileptics

What are antiepileptics?
What are antiepileptics used for?
Drug treatment
How do Antiepileptics work?
Side effects of Antiepileptics
Precautions when taking Antiepileptics
Interactions with other medicines

What are antiepileptics?

Antiepileptics are a class of drugs that try and prevent rapid, repetitive, stimulation of the brain that causes seizure activity such as in epilepsy. Members of this class of drugs include carbamazepine, valproate, lamotrigine, oxcarbazepine, gabapentin, levetiracetam, pregabalin, tiagabine, topiramate, vigabatrin, acetazolamide and sulthiame.

What are antiepileptics used for?

Antiepileptics are used for the prevention of seizures and associated complications. They are also indicated for acute treatment of seizures including status epilepticus and febrile seizures.

Drug treatment

Before commencing treatment non-epileptic causes such as breath-holding attack, arrhythmia, pseudoseizures may be excluded by your doctor. The epilepsy type is then classified on the basis of description of seizures, neurological examination, EEG findings and neuroimaging. It is advised to avoid precipitants if possible (eg drugs, sleep deprivation, alcohol withdrawal). Antiepileptic medication is started when the impact of further seizures outweighs the risks of treatment. Treatment is usually indicated when 2 or more seizures have occurred within 6-12 months, except when there is a clear avoidable precipitant or with some types of seizures but your doctor will determine this. The aim of treatment is to prevent seizure recurrence preferably with monotherapy to minimise adverse effects. Non-compliance is a common cause of therapy failure and hence it is important to comply with your doctor's recommended treatment. If the seizures are not controlled by the maximum tolerated dose of the first antiepileptic drug, it may be replaced by a second drug.

The second drug is added to the first and once the patient is stabilised on an adequate dosage, then the first drug is gradually withdrawn. If trials of monotherapy fail, polytherapy (using multiple drugs) is often used but adequate control of seizures is more difficult. Specific diagnosis of seizure type is the most important factor for drug selection however your doctor will chose the best treatment for you. Tegretol (Carbamazepine) is often considered to be the drug of choice for partial seizures. Epilim (Valproate) is regarded as first line treatment for generalised seizures. Lamictal (Lamotrigine) may be used in adults as monotherapy in partial and generalised seizures and it appears to be as effective as carbamazepine. It is also used as adjunctive treatment. Trileptal (Oxcarbazepine), a compound structurally related to carbamazepine, is effective as monotherapy or adjunctive treatment in partial seizures or generalised tonic-clonic seizures. It may be an alternative in patients unable to tolerate carbamazepine. Lyrica (pregabalin), Topamax (topiramate), Neurontin (Gabapentin), Keppra (levetiracetam) and Gabitril (tiagabine) are newer antiepileptic drugs which are mainly used as adjunctive treatment. Sabril (Vigabatrin) should be used only when all other appropriate drug combinations have failed. It may cause visual field defects in 20-40% of patients. Acetazolamide and sulthiame are approved for epilepsy. However, evidence for their clinical efficacy is limited and they are not in common use in Australia. The following is a summary table of drug choice in epilepsy:

	First line	Second line
Partial	Carbamazepine	Gabapentin, lamotrigine, levetiracetam, oxcarbazepine, phenobarbitone, phenytoin, pregabalin, tiagabine, topiramate, valproate
Generalised tonic-clonic	Valproate, carbamazepine	Lamotrigine, oxcarbazepine, phenobarbitone, phenytoin, topiramate
Absence	Valproate, ethosuximide	Clobazam, clonazepam, lamotrigine
Myoclonic	Valproate	Clobazam, clonazepam, phenobarbitone
Infantile spasms	Tetracosactrin (ACTH analogue), prednisolone	Clonazepam, nitrazepam, valproate, vigabatrin*
* use only if no safer alternative

The doctor will determine what the best treatment for you is.

How do antiepileptics work?

Antiepileptics have various mechanisms of actions to try and prevent rapid, repetitive, stimulation of the brain that causes seizure activity. Topamax (Topiramate), Tegretol (Carbamazepine), Epilim (Valproate) and Lamical (Lamotrigine) and work by blocking voltage gated sodium channels and hence prevent the repeated stimulation. Neurontin (Gabapentin) and Gabitril (Tiagabine) elevates GABA levels, a chemical messenger that stops repeated stimulation. Some if this activity is also demonstrated by Topamax (Topiramate). Lyrica (Pregabalin) is newer drug which is an analogue GABA with analgesic, anxiolytic and anticonvulsant activity.

Side effects of antiepileptics

The side effects for each type of medication vary but the most common side effects that occur in less than 10% of patients are:

Drowsiness
Ataxia
Dizziness
Blurred vision
Headache
Nausea
Vomiting
Diarrhoea
Constipation

Some of the rare serious side effects that can occur in less than 1% of patients are:

Exfoliative dermatitis
Stevens-Johnson syndrome
Systemic lupus erythematosus
Agranulocytosis
Psychiatric disorders

You may never experience any of these side effects but if you have any concerns talk to your doctor about it.

Anticonvulsant hypersensitivity syndrome

Carbamazepine, oxcarbazepine and phenytoin are associated with this rare, but serious syndrome. It usually occurs after 1 to 4 weeks of therapy and is characterised by fever, rash and systemic organ involvement. If you notice any unusual rashes or feel unwell, consult your doctor as soon as possible.

Precautions when taking antiepileptics

Pregnancy and antiepileptics

Antiepileptic medicines can cause birth defects in pregnancy. Your specialist will assess the risk and benefit of the medicines you are on to make the decision. The risk increases with the number of antiepileptic medicines taken. Phenytoin, valproate, carbamezapine and lamotrigine are all pregnancy Category D. Facial malformations, cardiac defects and fingers and nail deformities may occur with several antiepileptic drugs, in particular phenytoin (Dilantin), valproate (Epilim), carbamazepine (Tegretol) and lamotrigine (Lamictal). There is also an increased risk of spina bifida with valproate and, to a lesser extent, with carbamazepine. Topiramate is Pregnancy Category B3. There are no studies using Topiramate (Topamax) in pregnant women.

Your specialist will assess the risks and benefits and ensure that you are given the best treatment. He may recommend you use your medication at the lowest effective dose and also start folic acid supplementation four weeks prior to and continue for 12 weeks after conception. Please seek your doctor's advice if you are pregnant or planning to become pregnant.

Interactions with other medicines

This class of medications can interact with other medicines. Your doctor may try and avoid the combination or monitor you. If you have any concerns talk to your doctor about it. Hormonal contraceptives: If you start or stop taking hormonal contraceptives (e.g. "the pill") while taking antiepileptic medication your doctor may need to adjust the dose depending on how well your condition is being treated. Consult your doctor if you have any concerns.

Reference

Australian Medicines Handbook. [online]. Anticonvulsants. January, 2007. Available at URL: http://www.amh.net.au (last accessed 09/09/07).
Therapeutic Guidelines: Nuerology. [online]. Drugs used in Epilepsy. Version 2, 2003. Available at URL: http://www.tg.com.au (last accessed 09/09/07).
MIMS Australia. [online]. Tegretol. 2007. Available at URL: http://www.mims.com.au (last accessed 09/09/07).
MIMS Australia. [online]. Epilim. 2007. Available at URL: http://www.mims.com.au (last accessed 09/09/07).
MIMS Australia. [online]. Lamictal. 2007. Available at URL: http://www.mims.com.au (last accessed 09/09/07).
MIMS Australia. [online]. Trileptal. 2007. Available at URL: http://www.mims.com.au (last accessed 09/09/07).
MIMS Australia. [online]. Lyrica. 2007. Available at URL: http://www.mims.com.au (last accessed 09/09/07).
MIMS Australia. [online]. Topamax. 2007. Available at URL: http://www.mims.com.au (last accessed 09/09/07).