Buspirone Therapy for Localized Epilepsy
Condition: Anxiety Disorder; Seizures; Epilepsy; Partial Epilepsy; Depression
MeSH terms: Epilepsy; Seizures; Epilepsies, Partial; Anxiety Disorders
Intervention: Buspirone; Placebo
Intervention MeSH terms: Buspirone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Epilepsy; Temporal Lobe Epilepsy; Serotonin 1A Receptor; Seizures

Summary:

      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.

      Participants 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.
    

Eligibility criteria:

        -  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