Treatment of Epilepsy

The goal of epilepsy treatment is create a seizure free state within the individual, this may be achieved by means of pharmacological or surgical intervention, as well as the simple lifestyle changes, alone or in combinations.

Pharmacological treatment of Epilepsy

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The first call of treatment is the removal of factors that may provoke seizures, such as alcohol, drugs, or sleep deprivation.

Anti-convulsants form the mainstay of seizure prevention, successfully creating a seizure free state 60% of case. Anti-convulsants are selected to counter the effects and etiologies of the form of seizure and epileptic syndrome:

• Blockers of recurrent Sodium channel activation (Phenytoin, carbamazepine, oxcarbazepine)
• Enhancers of GABA action (Phenobarbital, benzodiazepines)
• Glutamate modulators (Topiramate, lamotrigine, felbamate)
• Binding site antagonists (Gabapentin, levetiracetam)
• T-channel calcium blockers (Ethosuximide, valproate)
• N- and L-calcium channel blockers (Lamotrigine, topiramate, zonisamide, valproate)
• H-current (a.k.a. funny current) modulators (Gabapentin, lamotrigine)
• Carbonic anhydrase inhibitors (Topiramate, zonisamide)

The above denotes the multiple and singular functionalities of different anti-convulsants. The table bellow gives a gross generalisation of the anticonvulsants used in the treatment of epileptic seizures:

Studies have shown Valporate is better tolerated by the body than topiramate, but has a higher efficacy than Lamotrigine, making it the drug of choice in the treatment of generalised and unclassified seizures. However Valporate is also known to have adverse effects during pregnancy thus prescription to women during childbearing years should be carefully considered.

The treatment of partial seizures is perhaps more complex, owing to a greater specificity of aetiology. Carbamazepine is the mainstay for therapy. Failing this adjunctive therapy with levetiracetam, tiagabine, gabapentin, or pregabalin may be considered, or even selected as for alternative monotherapies. Valporate has been shown to have similar efficacies Carbazepine, however studies have indicated the latter may be the better choice in complex partial seizures.

Many considerations have to be made when prescribing anti convulsants and should only be done by a qualified medical practitioner. Many anti-convulsants are known to seriously damage the liver including Valporate (especially dangerous to children). It has been shown in many instances that men are better able to tolerate certain drugs. Developing individuals and the elderly also exhibit different drug tolerances, and individuals who are or have suffered hepatic or renal dysfunctions have a reduced capacity to metabolise and remove drugs. The patients medical history, current medication and state of health will all significantly weigh on the drug selected to deal with the patients epileptic syndrome. It should also be noted that selecting inappropriate drug effects may exacerbate seizure susceptibility. Monotherapies are usually attempted first to avoid complications with the interactions of drugs and their effects, however a lack of response may require the administration of multiple drugs.

Some anticonvulsants are not approved by the food and drug administration (FDA) for uses in epilepsy treatment. These may be used in the treatment of unusual or difficult cases, and experimental trial studies. They include; acetozolamide, progesterone, adrenocorticotropic hormone, various corticotropic steroid hormones and bromide. New anti-convulsants are first tested in conjunction, and later in a head to head comparison with drugs of equivelant function, in order to search for similar or improved anti epileptic effects with fewer adverse side effects within given contexts.

Anticonvulsants act only to suppress seizures, and in instances may fail to prevent or even reduce attacks. These patients may candidates for alternative treatments.

Patients observed to be seizure free for an appropriate durations (2-5 year typically) may be candidates for the discontinuation of medication as are patients with syndromes which are outgrown, such as those experienced in childhood alone. The opportunity is normally carefully assessed prior to the termination of medication, MRI and EEG having to meet certain criteria of “normality”. About 75% of patients will experience a relapse, 50% of which will do so in the first 3 months, thus appropriate seizure precautions should be taken. Graudal “weening” from anti convulsants is commonly practiced.

Status epilepticus becomes more difficult to treat as it progresses, many treatments becoming ineffective at later stages caused by changes in receptor populations. Due to the potentially fatal nature of the condition, fast treatment is a must. Midazolam is the only drug absorbed fast enough for intramuscular, buccal or intra-nasal application. Rectal administration of diazepam (a benzodiazepine) and other drugs may also prove effective, but an intravenous route proves the fastest acting route. Entry to the brain must also be swift, thus drugs are selected for a high lipid solubility to effectively pass the blood brain barrier, though this may cause problems with accumulation in inappropriate areas, countered by an increase in the size of doses used.

The pharmacokinetics of anticonvulsants during seizures are prone to modulation by the form of seizure, especially in convulsive (tonic, clonic or tonic-clonic) seizures where a fall in blood pH is seen.