Patients with traumatic brain injury often experience a period of acute confusion that may
include agitation as they recover from their injuries. While this confusion generally
resolves with time, patients may pose increased risk of injury to themselves or others
during this period. Their behavior may also increase stress for family members and
interfere with their ability to benefit from rehabilitation therapies. A number of
different medications have been used to treat confusion to decrease agitation, decrease risk
of injury, and improve participation in rehabilitation therapies. To this point, there has
not been a research or scientific basis for knowing which medication is the best for a
specific patient. The overall goal of this study is to conduct a scientific investigation
to help determine which medication works best to treat confusion.
Study hypothesis: Amantadine will reduce the severity and number of symptoms of acute
confusion after traumatic brain injury.
Patients with TBI who require inpatient rehabilitation are frequently confused at the time
of admission for rehabilitation. Our investigations of confusion conducted as part of the
TBIMSM have clarified the nature of confusion in early recovery after TBI. Early confusion
(PTCS) has been found to be a complex syndrome characterized by disorientation, cognitive
impairment, restlessness, decreased level of daytime arousal, sleep disturbance, fluctuation
of symptoms, and psychotic-type symptoms. PTCS complicates early management of patients
with TBI, and may contribute to increased risk of injury to patients and hospital staff,
increased stress among family members and staff, decreased participation in therapies,
increased cost of care, and an increased likelihood of being discharged to psychiatric or
long-term care settings. These facts indicate the need for effective management of PTCS.
Consensus regarding optimal treatment of the cognitive and behavioral symptoms encountered
among patients with PTCS does not exist currently. While many agents have been tried to
address such symptoms in TBI, few have been investigated systematically. These
circumstances indicate the need for appropriate clinical trials to provide guidance to
clinicians for medical treatment of PTCS. In response, the NIDRR-Traumatic Brain Injury
Model System of Mississippi proposed a randomized, double-blinded, placebo-controlled,
parallel group trial for the pharmacological treatment of PTCS. The agent selected for this
clinical trial is amantadine, an NMDA and indirect dopamine agonist. This agent will be
compared to placebo on response measures of efficacy and safety.
Study hypothesis: Amantadine will reduce the severity and number of symptoms of PTCS.
- Acute Traumatic Brain Injury (≤90 days postinjury)
- Responsive (not fulfilling criteria for Minimally Conscious State)
- Meet PTCS criteria on 2 consecutive examinations (as determined by the Confusion
- Initial neurorehabilitation hospital admission
- Anticipated ≥2 week length-of-stay after meeting PTCS criteria
- Preexisting seizure disorder
- Prior history of hospitalization for psychiatric condition