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Regarding the usefulness in measuring the serum concentrations of antiepileptic drugs, it is often of value to do so with those drugs that are liable to cause toxic side effects such as carbamazepine, ethosuximide, phenobarbitone and phenytoin. In general, there seems to be little advantage in determining the serum concentrations of the newer, and better tolerated, antiepileptics.

Factors which influence the serum concentrations of the antiepileptic drugs depend on the chemical nature of the drug, the drug formulation and drug interactions and the time at which the blood sample is taken (usually at the trough concentration before the daily dose). In addition, the individual patient can cause changes in the drug concentration. Such factors include genetic and constitutional factors, such as the age and gender, the absorption of the drug (which is influenced by food and gastrointestinal function), the metabolism (which is affected by the hepatic enzyme status), the distribution of the drug (which is influenced by the serum protein concentration, nutritional status and pregnancy), and lastly the excretion (which is affected by renal disease).

In practice, the monitoring of the serum drug concentration is generally unnecessary but there are criteria which may help the clinician to decide when monitoring is appropriate. These include:

• Poor therapeutic response in spite of an adequate dose of the drug.

• Physiological or pathological conditions that are known to affect the kinetics of the drug (e.g. renal or liver disease, pregnancy)

• Minimizing the problems caused by the non-linear kinetics of the drug (e.g. phenytoin).

• Minimizing the problems caused by drug interactions.

• To assess the changes in bioavailability caused by changes in drug formulation.

It should be emphasized that the outcome of therapy in newly diagnosed patients is generally good. In about 70-80% of these patients, seizures will cease usually within a few years of treatment. In the case of such patients, the risk of subsequent recurrence is low (approximately 10% after a 5-year period without an attack) and most patients will be able to discontinue medication. The prognosis is worse if there is structural brain damage, severe epilepsy syndromes, a family history of epilepsy, a high frequency of tonic-clonic seizures before the start of therapy or in those patients with psychiatric or neurological disorders. EEG analyses have, in general, been shown to be a poor indicator of prognosis.

Limitations of current antiepileptic drug therapy

It has been estimated that drug therapy will fail in 10-20% of patients. In this situation the epilepsy is described as intractable and the goal of therapy should be changed to defining the best compromise between inadequate seizure control and drug-induced side effects. The concept of intractability is invariably fairly arbitrary. There are over 10 widely used antiepileptic drugs and far more combinations. The chances of a new drug controlling the seizures after five appropriate drugs have failed to do so has been estimated to be less than 5%. Thus from the practical point of view one may categorize a patient as intractable when at least five of the major antiepileptics have been shown to be ineffective.

Summary of the antiepileptic drugs used for different types of seizures

There is a dearth of good comparative data on the appropriate drugs to be used for different seizure types. The following table is based upon summaries published in standard monographs, several of which are mentioned in the references to this chapter:

For simple and complex partial seizures and secondary generalized tonic-clonic seizures, the first line drugs are - carbamazepine, valproate and phenytoin. Second line drugs include - acetazolamide, clobazam, clonazepam, ethosuximide, felbamate, gabapentin, lamotrigine, levetiracetam, oxacarbamazepine, primidone, tiagabine, topiramate and vigabactin.

For generalized absence seizures, first line treatment is with valproate or ethosuximide and second line treatment with acetazolamide, clobazam, clonazepam, lamotrigine, phenobarbitone and primidone.

For atypical absence, tonic and clonic seizures, first line treatment is with valproate and second line with acetazolamide, carbamazepine, clobazam, clonazepam, ethosuximide, felbamate, lamotrigine, oxacarbamazepine, phenobarbitone, phenytoin, primidone or topiramate.

Myoclonic seizures are best treated with valproate but, as a second choice, with clobazam, clonazepam, ethosuximide, lamotrigine, phenobarbitone, piracetam or primidone.

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