Amantadine enhancement of arousal and cognition after traumatic brain injury

OBJECTIVE: To determine the role of amantadine therapy for early arousal and improved cognition in traumatic brain injury (TBI). DATA SOURCES: Literature was accessed through MEDLINE (1950-August 2007) using the MeSH terms amantadine, brain injuries, cognition, and arousal. PubMed (through August 2007) terms included amantadine, traumatic brain injury, and cerebral injury. STUDY SELECTION AND DATA EXTRACTION: All studies of amantadine (used <6 mo after injury) for enhancement of arousal or cognition in patients with TBI were reviewed. DATA SYNTHESIS: Many cases of TBI are associated with frontal lobe injury As a dopamine agonist, amantadine is thought to be involved in frontal lobe stimulation. Two case reports, 3 retrospective studies, and 2 randomized, doubles blind, controlled trials of amantadine therapy for early arousal in TBI were identified and reviewed. Limitations of the available studies include open design, retrospective design, and heterogeneous brain injury types. Results have been inconsistent between studies, largely due to variability in designs, heterogeneity in patient populations, time following injury, and use of numerous different outcome measures. Despite these limitations, improvements in arousal and cognition, as documented by the Glasgow Coma Scale and other measures, have been observed in patients with TBI when amantadine has been initiated 3 days to 5 months after injury. CONCLUSIONS: At doses of 200-400 mg/day, amantadine appears to safely improve arousal and cognition in patients with TBI. Additional prospective controlled studies with homogeneous patient populations will better define the role of amantadine for early arousal.