Effect of antiepileptic drugs on spontaneous seizures in epileptic rats

The present study investigated whether spontaneously seizing animals are a valid model for evaluating antiepileptic compounds in the treatment of human epilepsy. We examined whether clinically effective antiepileptic drugs (AEDs), including carbamazepine (CBZ), valproic acid (VPA), ethosuximide (ESM), lamotrigine (LTG), or vigabatrin (VGB) suppress spontaneous seizures in a rat model of human temporal lobe epilepsy, in which epilepsy is triggered by status epilepticus induced by electrical stimulation of the amygdala. Eight adult male rats with newly diagnosed epilepsy and focal onset seizures were included in the study. Baseline seizure frequency was determined by continuous video-electroencephalography (EEG) monitoring during a 7 days baseline period. This was followed by a 2-3 days titration period, a 5-7 days treatment period, and a 2-3 days wash-out period. During the 5-7 days treatment period, animals were treated successively with CBZ (120 mg/kg/day), VPA (600 mg/kg/day), ESM (400 mg/kg/day), LTG (20 mg/kg/day), and VGB (250 mg/kg/day). VPA, LTG, and VGB were the most efficient of the compounds investigated, decreasing the mean seizure frequency by 83, 84, and 60%, respectively. In the VPA group, the percentage of rats with a greater than 50% decrease in seizure frequency was 100%, in the LTG group 88%, in the VGB group 83%, in the CBZ group 29%, and in the ESM group 38%. During the 7 day treatment period, 20% of the VPA-treated animals and 14% of the CBZ-treated animals became seizure-free. These findings indicate that rats with focal onset spontaneous seizures respond to the same AEDs as patients with focal onset seizures. Like in humans, the response to AEDs can vary substantially between animals. These observations support the idea that spontaneously seizing animals are a useful tool for testing novel compounds for the treatment of human epilepsy.