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

Neuropsychiatric Inventory (NPI) is a 40-item instrument evaluating 12 behavioral domains with prior use in TBI. NPI-Irritability domain (NPI-I) encompasses temper outbursts, mood fluctuations, abrupt anger, impatience, irritable disposition, and argumentative behavior. Assessment involves identifying if these behaviors are present and then scoring the most concerning manifestation on severity (1=mild to 3=severe) and frequency (1-4 scale, higher=greater occurrence). Domain totals (0-12 range) represent the product of severity and frequency ratings for the predominant symptom.

Neuropsychiatric Inventory (NPI) is a 40-item instrument evaluating 12 behavioral domains with prior use in TBI. NPI-Aggression domain (NPI-A) captures emotional reactivity, resistance to activities, obstinate conduct, lack of cooperation, verbal outbursts, profanity, and physical aggression. Assessment involves identifying if these behaviors are present and then scoring the most concerning manifestation on severity (1=mild to 3=severe) and frequency (1-4 scale, higher=greater occurrence). Domain totals (0-12 range) represent the product of severity and frequency ratings for the predominant symptom.

Neuropsychiatric Inventory (NPI) is a 40-item instrument evaluating 12 behavioral domains with prior use in TBI. NPI-Irritability domain (NPI-I) encompasses temper outbursts, mood fluctuations, abrupt anger, impatience, irritable disposition, and argumentative behavior. Assessment involves identifying if these behaviors are present and then scoring the most concerning manifestation on severity, frequency, and distress. The NPI-I Distress quantifies the emotional burden experienced by the rater regarding the most troublesome behavior using a 6-point rating system 0 to 5 (lower scores=lower distress).

Neuropsychiatric Inventory (NPI) is a 40-item instrument evaluating 12 behavioral domains with prior use in TBI. NPI-Aggression domain (NPI-A) captures emotional reactivity, resistance to activities, obstinate conduct, lack of cooperation, verbal outbursts, profanity, and physical aggression. Assessment involves identifying if these behaviors are present and then scoring the most concerning manifestation on severity (1=mild to 3=severe) and frequency (1-4 scale, higher=greater occurrence). Domain totals (0-12 range) represent the product of severity and frequency ratings for the predominant symptom. The NPI-A Distress quantifies the emotional burden experienced by the rater regarding the most troublesome behavior using a 6-point rating system 0 - 5 (lower scores=lower distress).

A self-report measure of overall neurobehavioral function. St Andrew's-Swansea Neurobehavioural Outcome Scale (SASNOS) is a 49-item observer-rated measure of neurobehavioral dysfunction in acquired brain injury. This study utilized the 15-item aggression subscale (overt aggression, irritability, and provocative behavior). The scale uses a 7-point Likert scale ("never" to "always") for items, and raw total scores are converted into standardized T-scores (M=50),(SD=10). Higher score reflects less aggression with a clinically relevant range usually extending from below (30) (indicating significant disability/high aggression) to (70) or higher (fewer symptoms).

A self-report measure of overall change. Global Impression of Change (GIC) employs a 5-point Likert scale whereby observers rate perceived changes in the participant from significant improvement to substantial deterioration. High score reflects worsening. Score ranges 1 to 5: 1-much improved, 2-mildly improved, 3-unchanged, 4-mildly worsened, 5-much worsened.

A measure of depression that maps on to Diagnostic and Statistical Manual (DSM) criteria for depression. Personal Health Questionnaire-9 (PHQ-9) is a 9-item self-report depression screening based on DSM-V criteria with validity and reliability in TBI populations. Higher scores indicate greater presence of recent depression symptoms. PHQ-9 has a total score range of 0 to 27, based on 9 items scored from 0 ("not at all") to 3 ("nearly every day"). It is a validated tool for assessing depression severity in various populations, including those with traumatic brain injury.

A self-report measure of anxiety. Generalized Anxiety Disorder-7 (GAD-7) is a 7-item self-report questionnaire assessing generalized anxiety disorder symptoms based on DSM-V criteria. Total score ranges from 0 to 21, where higher scores indicate greater severity of anxiety. Scores are categorized as: 0-4 (Minimal), 5-9 (Mild), 10-14 (Moderate), and 15-21 (Severe). A score of 10 or higher is commonly used as the cutoff for clinical screening.

A self-report measure of overall impact of anger on quality of life. TBI-Quality of Life (TBI-QOL) Anger is a 10-item measure of the continuum of anger in TBI populations that is calibrated with the Patient Reporter Outcome Measurement Information System (PROMIS) scales. The measure assesses self-reported frequency and intensity of anger symptoms-including irritability, frustration, and outward aggression-in individuals with traumatic brain injuries. A T-score metric is used, typically ranging from roughly 30 to 80+, where a mean of 50 and a standard deviation (SD) of 10 represent the general population. Higher scores indicate more severe anger.

Clinician rating of overall change. The Clinical Global Impressions (CGI) scale is a 3-item, 7-point observer-rated instrument used in psychiatry to assess treatment response. It measures severity of illness (1-7), global improvement (1-7), and the efficacy index (0-4) or specific combinations of therapeutic/side effects). Lower scores generally indicate better outcomes (e.g., 1="Very much improved"). CGI-Improvement (CGI-I) (1-7): Assesses change from baseline, with 1 indicating "very much improved" and 7 indicating "very much worse".