Amantadine to improve neurorecovery in traumatic brain injury-associated diffuse axonal injury: a pilot double-blind randomized trial.

Abstract

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.

PARTICIPANTS:

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.

MAIN OUTCOME MEASURES:

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.

• Authors: Jay M Meythaler, Robert C Brunner, Alice Johnson, Thomas A Novack
• Journal: The Journal of head trauma rehabilitation (J Head Trauma Rehabil) Vol. 17 Issue 4 Pg. 300-13 (Aug 2002) ISSN: 0885-9701 [Print] United States
• PMID: 12105999 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Dopamine Agents
• Amantadine

Topics

• Accidents, Traffic
• Adolescent
• Adult
• Aged
• Amantadine (administration & dosage)
• Axons (drug effects, pathology)
• Brain Injuries (diagnosis, drug therapy)
• Cross-Over Studies
• Dopamine Agents (administration & dosage)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Administration Schedule
• Female
• Follow-Up Studies
• Glasgow Coma Scale
• Humans
• Injury Severity Score
• Male
• Middle Aged
• Pilot Projects
• Probability
• Recovery of Function
• Statistics, Nonparametric
• Treatment Outcome