Abstracts

RATIONALE: Acute efficacy studies of potentially new antiepileptic drugs are difficult to perform since most epilepsies show a variability in occurrence of seizures and epileptiform discharges. In photosensitive patients epileptiform discharges can be evoked at any time by intermittent photic stimulation (IPS) in the laboratory. The frequencies to which an individual patient is sensitive so called photosensitivity range- is relatively stable and reflects the liability of seizures in daily life. Although, the majority of photosensitive patients belong to the idiopathic generalised epilepsies, a photoparoxysmal response (PPR) to IPS can also be found in other epilepsy types. Whether the efficacy of the antiepileptic activity predicted by the model can be extrapolated to different epilepsy syndromes, also without photosensitivity, can be obtained posterior clinical studies. Such a comparison will provide a proof of concept of this model. METHODS: A meta-analysis of twelve drug trials (mainly performed in our center)has been performed using this model. Abolishment or clear diminishment of the PPR is considered as measure of pharmacodynamic. The results obtained in the model (early phase II)were compared with subsequent clinical studies (phase III and IV). RESULTS: The recruited number of patients varied from 4 to16, mostly women, with an age ranging from 17-39 yrs. Most of the patients had generalised epilepsies. The studied drugs (carbamazepine, lamotrigine, valproic acid, ethosuximide, levetiracetam etc.) have different mechanisms of actions and have been proven effective in different types of epilepsies. One drug, Org 6370, proved to be provocative in the model and has not been developed as an antiepileptic drug. CONCLUSIONS: This model can be used as a quick screening method to assess the antiepileptic power of the compound. The predicted potential antiepileptic effect, may extent not only to those patients with a photosensitive epilepsy, but also may include other syndromes without this trait.