In a first-of-its-kind study,1 researchers at the University of Pittsburgh Medical Center have found that amantadine - a drug originally developed as a medication used to treat or prevent illness caused by the flu virus, and later shown to improve symptoms of Parkinson's disease and cognitive function in patients with serious brain, spinal cord, or nerve-related illnesses and injuries - may be useful in treating adolescents with post-concussion syndrome.
Given 100 mg of amantadine twice daily at breakfast and lunch, a small treatment group of 25 student-athletes (ranging in age from 13 to 19 and with an average age of 15.54 years) who had not spontaneously recovered from concussion following a period of cognitive and physical rest, and were still experiencing persistent neurocognitive deficits and concussion symptoms at 3 to 4 weeks post-injury, reported a significant decrease in reported symptoms as well as improvements in verbal memory and reaction time on neurocognitive tests compared to a control group of concussed student-athletes with post-concussion syndrome treated conservatively (i.e., rest) and without medication.
The findings "provides tentative support for the efficacy of amantadine as pharmacological treatment for patients who fall outside of the normal recovery trajectory (i.e., more than 3 weeks) following concussion," writes lead author, Cara Camilio Reddy, MD, Director, Brain Injury Program, Department of Physical Medicine and Rehabilitation and Medical Advisor to the Sports Concussion Program in the Department of Orthopedic Surgery at the University of Pittsburgh Medical Center.
"These results highlight one possible treatment for patients with prolonged recovery from concussion," Reddy says, although it "may not be the treatment of choice for all patients with post-concussive symptoms" because "individualized concussion management requires [an] in-depth interview to evaluate the symptoms and to tailor a management plan based upon each individual's symptom profile."
Earlier placebo-controlled double blind studies of the use of amantadine had yielded inconsistent results, one showing no statistical effect of the drug on cognitive function,2 the other reporting consistent trends towards rapid functional improvement.3 Both studies, however, were of adults.
Due to limitations in the University of Pittsburgh study (small sample size, retrospective nature, a non-randomized design resulting in both subjects and clinicians being aware the drug was being used which could have resulted in placebo and experimenter bias), the study authors said their results "should be viewed cautiously" until double-blind randomized control trials of the efficacy of amantadine following concussion in a sufficiently large sample could be conducted to collaborate the study's findings.
As a result, until such further studies are done, amantadine should be considered a potential, as opposed to proven, therapy for the treatment of concussive brain injury. As with all medications, amantadine has side effects, but is generally well tolerated and is so safe that the current FDA approval for the drug is for use by healthy children during an influenza outbreak, in order to prevent them from getting the flu. It use cannot be stopped abruptly because of the risk of developing malignant hyperthermia, a medical condition that causes painful rigidity of the muscles and high fevers.
Because of a concern for the potential for birth defects in the children of women who are pregnant or who become pregnant while taking amantadine, careful thought should be given to the potential risks and benefits of taking the drug when deciding whether it should be used to treat concussion.
1. Reddy CC, Collins M, Lovell M, Kontos A. Efficacy of AmantadineTreatment on Symptoms and Neurocognitive Performance Among Adolescents Following Sport-Related Concussion. J Head Trauma Rehab 2012: DOI: 10.1097/HTR.0b013e318257fbc6 (published online ahead of print)(accessed December 13, 2012).
2. Schneider WN, et. al. Cognitive and behavioural efficacy of amantadine in acute traumatic brain injury:an initial double-blind placebo-controlled study. Brain Inj. 1999;13:863-872,
3. Meyerthaler JM, et. al. Amantadine to Improve Neurorecovery in Traumatic Brain Injury-Associated Diffuse Axonal Injury: A Pilot Double-blind Randomized Trial. J Head Trauma Rehabil. 2002;17:300-313.
Adapted from Kids, Sports, and Concussion by William P. Meehan, III, M.D. (Praeger 2011). Updated December 14, 2012 to include the new study by Reddy et. al.
