OBJECTIVE: To initiate a pilot clinical trial assessing the safety, tolerability and efficacy of the 5HT1A receptor agonist buspirone in patients with localization-related epilepsy. Buspirone is a 5HT1A receptor agonist that is approved for the treatment of anxiety disorders. Patients with localization-related epilepsy have reduced 5HT1A receptor binding on 18FCWAY positron emission tomography (PET). Increasing neurotransmitter activity at 5HT1A receptor sites may ameliorate seizures. STUDY POPULATION: Forty patients with localization-related epilepsy DESIGN: A randomised, double-blind, placebo-controlled cross-over, phase II clinical trial. The trial will have a screening phase in which each patient will undergo physical and neurological examination, and standard blood tests, followed by a one month baseline phase. At the end of baseline, patients who qualify will have neuropsychological, anxiety, and mood evaluation, FCWAY PET and MRI (if imaging was not performed already). During the subsequent first study phase, patients will be randomized to buspirone or matching placebo. After completion of the first study phase, patients will be crossed over to the alternate study arm. At the end of the study, any patient who wishes to do so may remain on open-label buspirone. OUTCOME MEASURES: 1. Difference in seizure rate comparing the 3 month placebo and active study phases 2. Neuropsychological, anxiety, and mood indices comparing the 3 month placebo and active study drug phases
- INCLUSION CRITERIA: - Patients may be male or female. - Patients will be aged 18 65 - Patients must have at least 3 seizures during the one-month baseline. - Localization-related epilepsy diagnosed by standard clinical criteria that has not responded to treatment with two standard antiepileptic drugs either sequentially or in combination. - Patients must be able to provide informed consent - Patients must be able to remain on their baseline AED drugs and doses throughout the study - Patients must be able to use seizure calendars to record seizures throughout the trial. EXCLUSION CRITERIA: - Pregnant patients will not participate in the study. - During the study, women of child-bearing potential must use a reliable method of birth control and will have pregnancy testing throughout the protocol. - Use of any alcohol or recreational drugs starting two weeks before entering baseline and for the duration of the study. - Patients on medications with potential for a clinically significant interaction with buspirone, including MAO inhibitors, clozapine, zolpidem, hypnotics, hydromorphone derivatives, oxycodone, and diltiazem. - Current treatment for psychiatric disorder other than depression, anxiety or bipolar disorder. - Patients with a diagnosis of schizophrenia. - Current treatment for another significant medical disorder, such as diabetes, or heart disease, or an untreated disorder, that might interfere with the study. - Calculated Creatinine clearance of less than 80 ml/min calculated with the Cockcroft-Gault formula: - Clcr = [(140-age) times ideal body weight in Kg] times (0.85 if female) divided by (72 times serum Cr in mg/dL) - Evidence of impaired liver function based on serum chemistries. - Inability to participate in the study procedures, such as MRI, PET, seizure and adverse event recording, or drug titration