Effects of Antiepileptic Drugs on Brain Excitability

Objectives. Epilepsy is a condition characterized by abnormally increased cortical excitability, and antiepileptic drugs (AEDs) control epilepsy by reducing cortical excitability. Serum blood levels presently represent the standard measure utilized to track the therapeutic effects of AEDs. However, peripheral blood levels do not always reflect brain levels, or provide direct information on cortical excitability. Transcranial magnetic stimulation (TMS) is a non-invasive technique that allows accurate measures of this parameter. The purpose of this protocol is to test the hypothesis that TMS measures of cortical excitability will correlate with serum blood levels of AEDs, and reflect clinical effects on cortical function directly in healthy volunteers. This information is crucial to reach the ultimate goal of developing a reliable quantitative measurement of central physiological effects of AEDs in epileptic patients. Study Population. 40 normal volunteers aged 18 to 55 years will be recruited for this study. Design. Subjects will be assigned to either of two groups, with each group receiving one of the following drugs; carbamazepine (CBZ), and lamotrigine (LTG). Measures of cortical excitability will be performed using TMS in various drug treatment phases: at baseline (before drug intake); during the AED induction period (once a day for the first 5 days), after 12 days of drug intake at the maximum dose during steady state; and 3, 7, and 14 half-lives after, and finally three weeks after abrupt drug withdrawal. Blood sampling for drug levels will be performed at each TMS study. Outcome Measures. The primary outcome variables will be MEP size, measured from recruitment curves. MEP size difference from baseline will be compared to the serum drug level for each drug.