REVIEW – December 2005

Drug resistant epilepsy. Current options for management


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Modern community based studies have shown that approximately 36% of persons with epilepsy remain refractory to antiepileptic drug (AED) treatment. In Estonia, up to 8400 patients with drug resistant epilepsy can be expected. In the last decade, several new AEDs were marketed – oxcarbazepine (OXC), lamotrigine (LTG), topiramate (TPM), gabapentin (GBP), vigabatrin (VGB), tiagabin (TGB), levetiracetam (LEV), and zonisamide (ZNS). The first four are registered and available in Estonia. Evidence-based reviews are hence needed to provide practicing physicians with adequate knowledge for making a rational choice from among the available drugs for individual patients.

Numerous comparative trials have revealed that new drugs are often as efficacious as conventional drugs, while their tolerability is even better. However, the methodology of these trials is frequently criticised. A sub commission of the American Academy of Neurology has evaluated the available data of new AEDs, and concluded that most new compounds are characterised by proven efficacy as add-on therapy in patients with refractory partial epilepsy, and only LTG and TPM have been shown to be effective against generalised seizures. Until now, relatively few studies have been conducted to evaluate these drugs as monotherapy for newly diagnosed epilepsy. Only OXC, LTG, TPM and GBP have been provided with sufficient data to conclude that they are as efficient as conventional drugs but have less adverse effects in monotherapy. Thus, UK guidelines, as well as Estonian guidelines, recommend that a new AED should be considered only if there is no benefit from a conventional AED, or in case it is contraindicated.

A recent suggestion is also to provide more aggressive polytherapy for resistant epilepsy as early as possible. The prognosis of epilepsy can be determined in most patients early in the course of the illness, i.e. in those with symptomatic/lesional epilepsy, ineffective first AED, high pre-treatment number/frequency of seizures etc. When combining this knowledge with result from recent studies, which have reported that rational duotherapy does not end up in higher toxicity compared with alternative monotherapy, it is reasonable to start duotherapy as early as poor response to medication is revealed.

One of the recommended strategies is a mechanistic approach based on the modes of action of AEDs. The mechanisms of AEDs fall into a number of general categories. Combination of drugs with similar modes of action is discouraged, and combination of drugs with different mechanisms is preferred.

Surgical methods for treatment of epilepsy should be considered if the refractoriness of the illness is established. It is especially effective against a potentially operable structural abnormality, such as mesial temporal sclerosis. Another rapidly developing surgical method is vagus nerve stimulation for the non-resective etiology of epilepsy. The work-up for epilepsy surgery includes EEG-videotelemetry (VTM) whose goal is to record ictal events. VTM is available in Estonia since 2002, and a team of epilepsy surgery programme is working at the Department of Neurology and Neurosurgery, the University of Tartu.