engleski

Medication treatment of epilepsies

In 1938 Merrit and Putnam discovered phenytoin and separated antiepileptic potential of the drug from sedation effects of earlier drugs. Since then we have at least 14 major antiepileptic drugs (AED) on the world market: primidone, ethosuximide, diazepam, carbamazepine, clonazepam, valproate, felbamate, gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, zonisamide and levetiracetam, in order of their appearance. However, most studies show a similar efficacy of all AEDs, but differentiate them by the common side-effects. When Mattson et al. published the first randomized, double-blind, placebo-controlled study in 1985, comparing carbamazepine, phenobarbitone, phenytoin and primidone, they concluded the unsatisfactory status of AEDs. The main focus of this lecture is whether something has changed in efficacy and specificity of new AEDs for treating and curing epilepsy, and not only controlling seizures, thirty years later. There is evidence that AEDs change concentration of many common drugs prescribed to patients with medical comorbidity and the opposite is true as well. Many “ common” medications change serum levels of AEDs ; such as salicilates, antibiotics and pain killers. In addition, there are important pharmacokinetic interactions among the AEDs, usually due to protein binding or enzyme inducement. Special groups, like women in childbearing age, breast-feeding mothers, children, elderly and mentally handicapped require special considerations when selecting an AED. These are areas of particularly strong research today, and databases including epilepsy patients in these categories are getting larger. Patients with epilepsy and psychiatric comorbidities require additional evaluation. Multiple groups showed that self-reported quality of life scores of epilepsy patients significantly depend on their mood status. Therefore, to preserve their life quality, the medication treatment should be optimized and indications for use of antidepressants, antipsychotics or anxyolytics should be appropriately made. Do AEDs alter the course of epilepsy? It appears that AEDs can impact a long-term outcome in several ways: both negative and positive. Examples of negative impact are changes in resistance glycoproteins at the blood-brain barrier, development of tolerance and cross-tolerance, and the AEDs might treat seizures but not epilepsy. All of them are more or less neurotoxic and have clear side-effects. Positive impact of AEDs is their protection against the epileptogenic effects of acute seizures and, some of them possibly offer neuroprotection. Long-term seizure-free patients are candidates for AED discontinuation. Some of the parameters that might help neurologists in this decision are: seizure-free patient for 2 or more years on AEDs ; single seizure-type, well-controlled from the start ; normal neuro exam and normal IQ ; and normalization of EEG during treatment. In conclusion, today, 30 years after the Mattson et al. study we know that current AEDs are capable of suppressing seizures, but lack evidence of antiepileptogenicity. They have no impact on the natural history of epilepsy and cannot prevent epilepsy. Further, new drugs have not changed the proportion of drug resistant patients, which is still 30%. What we should be aware is that when 2-3 AEDs in sufficient doses have failed to control seizures, evaluation for epilepsy surgery should be considered. A future drug-of-choice should have a long-term safety, good tolerability, high efficacy, minimal or no interaction potential and allow good quality of life.

Epilepsy; diagnosis; medication

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