Traumatic brain injury (TBI) is one of the most significant causes of disability to able bodied persons in the most productive period of their lives. The most common cause is high-speed transportation accidents, and these result in a mechanism of injury commonly described as diffuse axonal injury (DAI). DAI causes a reduction in the turnover of dopamine in the brain. Basic science research has suggested that increasing dopamine turnover at the synaptic level may have a beneficial effect on recovery from brain injury. One medication, Amantadine, has been the subject of considerable interest and clinical use. It stimulates the release of dopamine from the presynaptic neuron, inhibits the re-uptake of dopamine, may directly interact with post-synaptic dopamine receptors and is a weak N-methyl-D-aspartate (NMDA) antagonist. The concept study proposed herein will evaluate the early clinical use of Amantadine in TBI. This concept study is supported by the outcomes of a pilot study performed at UAB. However, the definite beneficial effect of Amantadine on brain injury recovery has never been demonstrated. Considering the widespread clinical application of Amantadine in TBI patients, a well-controlled prospective multicenter clinical trial should be carried out. This concept study, or any other(s) selected, will contribute to the multicenter TBI Clinical Trials Network. As Amantadine is generically available, there is little interest in it by the private sector. The study design is a single case double blind, randomized controlled trial. Utilizing well established outcome measures, including behavioral and cognitive, the investigators will attempt to establish the efficacy and side effects of Amantadine in the acute stages of recovery from TBI. This research has the significant possibility of reducing the disability and economic burden of these patients.
