Buspirone Therapy for Localized Epilepsy
Buspirone Therapy for Localized Epilepsy
Background:

 - Buspirone is a drug that is approved for the treatment of anxiety in adults. Studies
 suggest that buspirone might act on parts of the brain that can increase certain levels of
 brain activity. Increasing this brain activity may help decrease epileptic seizures that come
 from certain parts of the brain. Researchers want to see if buspirone can reduce seizure
 frequency in people with seizures who are already taking antiseizure medication.

 Objectives:

 - To test whether buspirone can reduce the frequency of seizures in people whose seizures
 seem to start from one part of the brain.

 Eligibility:

 -  Individuals between 18 and 65 years of age who have seizures coming from one or more
 places in the brain.

 -  Participants must have tried at least two different antiseizure medications. They must
 also have had at least three seizures during a 1-month observation period while on
 current medicines.

 Design:

 -  Participants will have a screening visit with a physical exam and medical history.
 Participants will complete mood and memory testing scales. Blood, urine, and saliva
 samples will be collected.

 -  Participants will have a magnetic resonance imaging scan to evaluate brain structures
 that relate to epilepsy. They will also have a positron emission tomography scan to look
 at parts of the brain that are affected by buspirone.

 -  Participants will start taking a study drug (either buspirone or placebo) twice daily.
 They will keep a calendar of seizures and record any side effects. Treatment will be
 monitored with clinic visits and blood samples.

 -  After 12 weeks on the study drug, participants will gradually stop taking either the
 placebo or buspirone over two weeks. They will stay off the drug for another 2 weeks.

 -  After 2 weeks, participants will start taking a study drug that is the opposite of the
 one they had before. They will keep a calendar of seizures and record any side effects.
 Treatment will be monitored with clinic visits and blood samples.

 -  After 12 weeks on the study drug, participants will gradually stop taking either the
 placebo or buspirone.

 -  Participants will have a final followup visit with additional blood tests, mood and
 memory testing scales and imaging studies.
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