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Phase 4 N=81 Randomized Quadruple-blind Treatment

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

Traumatic Brain Injury

Enrolled (actual)
81
Serious AEs
1.2%
Results posted
Feb 2026
Primary outcome: Primary: Neuropsychiatric Inventory-Irritability Domain - Observer-rated Proportion Improved ≥ 3 Points Baseline to Day-91 — 30; 31 Participants

Study Design & Population

Study type
Interventional
Phase
Phase 4
Interventions
Buspirone (Drug); Placebo (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Indiana University
Primary completion
Sep 2025

Outcome Measures

OutcomeResultp-value
PRIMARY
Neuropsychiatric Inventory-Irritability Domain - Observer-rated Proportion Improved ≥ 3 Points Baseline to Day-91
30; 31
SECONDARY
Neuropsychiatric Inventory-Aggression Domain - Observer-rated Proportion Improved ≥ 3 Points Baseline to Day-91
28; 27
SECONDARY
Neuropsychiatric Inventory-Distress Irritability Domain - Observer-rated
2.0; 1.7
SECONDARY
Neuropsychiatric Inventory-Distress Aggression Domain - Observer Rated
1.5; 1.3
SECONDARY
St. Andrews-Swansea Neurobehavioural Outcome Scale - Observer-rated
51.7; 53.1
SECONDARY
Global Impressions of Change - Observer-rated
2.8; 2.7
SECONDARY
Personal Health Questionnaire - Participant-rated
5.3; 5.2
SECONDARY
Generalized Anxiety Disorder - Participant-rated
6.0; 4.8
SECONDARY
Traumatic Brain Injury-Quality of Life Anger - Participant-rated
50.8; 51.0
SECONDARY
Clinical Global Impressions -- Global Improvement -- Clinician Rated.
2.4; 2.1

Summary

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.

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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01821690). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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