Amantadine for the Treatment of Traumatic Brain Injury Irritability and Aggression: A Multi-site Study

Inclusion Criteria: * Closed head injury (defined as impaired brain function resulting from externally inflicted trauma without penetrating injury) at least 6 months prior to enrollment * Irritability that is either new or worse than the level of irritability before the traumatic brain injury, by report of the Observer or person with TBI * Age at time of enrollment: 16 to 75 years * Voluntary informed consent and authorization of participant and informant * Subject and informant willing to comply with the protocol * Informant-rated NPI Irritability Domain score 6 or greater (moderate-to-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 or during the 90-day participation * No change in therapies or medications planned during the 90-day participation * No surgeries planned during the 90-day participation * Vision, hearing, speech, motor function, and comprehension sufficient to complete interviews * 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 irritabi…