Buspirone for the Treatment of Traumatic Brain Injury (TBI) Irritability and Aggression

The purpose of this study is to improve behavior control displayed by persons with traumatic brain injury by assessing effectiveness of treatments for post-TBI irritability and aggression.

PURPOSE OF PROJECT: To study the effect expressed by persons with TBI through assessment of buspirone effectiveness for post-traumatic irritability and aggression and development of an irritability/aggression impact measure.

SUMMARY OF PROJECT: It is anticipated that 74 subjects with 74 corresponding subject observers will be recruited for the treatment study. Subjects will be recruited from community and self-referrals.

Interested potential participants will be scheduled for an in-person screening visit. Subjects who consent and qualify will be randomized in a 1:1 ratio, buspirone or placebo. Stratification to randomization group will occur based on the presence of major or minor depression (defined by PHQ-9 total score \>5). Randomized subjects will receive active treatment or placebo. There will be 4 clinic visits. Visits will occur at baseline, for consenting and screening, day 35, day 63 and day 91. At all 4 clinic visits, both the subject and the observer will be given questionnaires regarding the subject's behavior and mood. Day 91 ends the period of the randomized clinical trial phase of the study and the subjects will begin the 1 month continuation phase of the study in which all participants receive active buspirone.

The following questionnaires will be used as measures of irritability and aggression for the subject and the observer: Neuropsychiatric Inventory (NPI \& NPI-Distress), Aggression \& Irritability Impact Measure (AIIM) and Global Impression of Change.

The following questionnaires will be dispensed to the subject only: TBI-Quality of Life-Anger, Personal Health Questionnaire (PHQ-9), Generalized Anxiety Disorder (GAD-7), PTSD Checklist Civilian (PCL-C), and Glasgow Outcome Scale Extended (GOS-E) The Investigator will complete the Clinical Global Impression of change at Visits 1, 2, 3, and 4. History and Physical Exam, creatinine level (kidney function) and liver function tests will be obtained for eligibility. Serum pregnancy tests will be drawn at screening for females of childbearing potential.

Eligibility Criteria:
Inclusion Criteria:

* Closed head injury (impaired brain function resulting from externally inflicted trauma without penetrating injury as defined below) at least 6 months prior to enrollment
* Irritability that is either new or worse than level of irritability before the traumatic brain injury, by report of observer or person with TBI
* Age at time of enrollment: 18 to 70 years
* Voluntary informed consent of patient and observer
* Subject and observer willing to comply with the protocol
* Observer-rated NPI Irritability Domain score 6 or greater to include only moderate-severe irritability
* Medically and neurologically stable during the month prior to enrollment.
* If taking antidepressant, anxiolytic, hypnotic, or stimulant medications, no change anticipated in these medications during the month prior to enrollment
* No change in therapies or medications planned during the 91-day participation
* No surgeries planned during the 91-day participation
* Vision, hearing, speech, motor function, and comprehension sufficient for compliance with all testing procedures and assessments
* Observer (e.g.: family member, close friend, employer) with whom subject interacts sufficiently to observe occurrences of irritability. The observer interacts with the participant for a period long enough and of a nature to be able to judge the participant's irritability. The interactions would need to be adequate to judge observer distress over the irritability, severity of irritability and frequency of irritability on the following scale: \< once weekly; once per week; several times per week, but not every day; essentially continuous.

Exclusion Criteria:

* Potential subject without a reliable observer
* Penetrating head injury as defined by head injury due to gunshot, projectile or foreign object
* Injury \< 6 months prior to enrollment
* Ingestion of buspirone during the month prior to enrollment
* Inability to interact sufficiently for communication with caregiver
* History of schizophrenia or psychosis
* Diagnosis of progressive or additional neurologic disease
* Clinical signs of active infection