Amantadine to improve neurorecovery in traumatic brain injury-associated diffuse axonal injury: a pilot double-blind randomized trial.
BACKGROUND
Traumatic brain injury (TBI) caused by a high-speed transportation accident results in a mechanism of injury commonly described as diffuse axonal injury (DAI), which is associated with a reduction in dopamine turnover in the brain. Because of its affect on both dopamine and N-methyl-D-aspartate (NMDA) channels, amantadine has been the subject of considerable interest and clinical use in acute TBI.


METHODS
In this study, 35 subjects, who had a TBI in a transportation accident and were initially seen with a Glasgow Coma Scale score of 10 or less within the first 24 hours after admission, were randomly assigned to a double-blind, placebo-controlled, crossover design trial.


METHODS
Amantadine, 200 mg, or placebo was each administered for 6 weeks (12 weeks total) to patients who were recruited consecutively.


RESULTS
There was an improvement in the Mini-Mental Status (MMSE) scores of 14.3 points (P =.0185), Disability Rating Scale (DRS) score of 9.8 points (P =.0022), Glasgow Outcome Scale (GOS) score of 0.8 points (P =.0077), and in the FIM Cognitive score (FIM-cog) of 15.1 points (P =.0033) in the group that received amantadine during the first 6 weeks (group 1), but there was no improvement in the second 6 weeks on placebo (P >.05). In group 2 (active drug second 6 weeks), there was an improvement in the MMSE of 10.5 points, in the DRS of 9.4 points (P =.0006), in the GOS of 0.5 points (P =.0231), and in the FIM-cog of 11.3 points (P =.0030, Wilcoxon signed rank) spontaneously in the first 6 weeks on placebo (P =.0015). However, group 2 gained a statistically significant additional 6.3 points of recovery in the MMSE (P =.0409), 3.8 points in the DRS (P =.0099), 0.5 points in the GOS (P =.4008), and 5.2 points in the FIM-cog (P =.0173, Wilcoxon signed rank) between the sixth week and the twelfth week of treatment on the active drug.


CONCLUSIONS
There was a consistent trend toward a more rapid functional improvement regardless of when a patient with DAI-associated TBI was started on amantadine in the first 3 months after injury.
Meythaler
Jay M
JM
Department of Physical Medicine & Rehabilitation, Spain Rehabilitation Center R157, School of Medicine, University of Alabama at Birmingham, 619 6th Avenue, Birmingham, AL 35249-7330, USA. jmeythal@uab.edu
Brunner
Robert C
RC
Johnson
Alice
A
Novack
Thomas A
TA
D000063:Accidents, Traffic; D000293:Adolescent; D000328:Adult; D000368:Aged; D000547:Amantadine / Q000008:administration & dosage*; D001369:Axons / Q000187:drug effects* / Q000473:pathology; D001930:Brain Injuries / Q000175:diagnosis* / Q000188:drug therapy*; D018592:Cross-Over Studies; D015259:Dopamine Agents / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D015600:Glasgow Coma Scale; D006801:Humans; D015601:Injury Severity Score; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011336:Probability; D020127:Recovery of Function; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
D015259:Dopamine Agents; D000547:Amantadine