Efficacy of Amantadine Treatment on Symptoms and
Neurocognitive Performance among Adolescents Following Sports-Related

Reddy CC, Collins M, Lovell M, Kontos AP. J Head Trauma
Rehabil. 2012 May 18. [Epub ahead of print]

Medications that improve the transmission of dopamine, a neurotransmitter, have been shown
to improve functional outcomes in animal
concussion.  Amantadine, a dopaminergic agent, has recently
been shown through preliminary research and anecdotal evidence to improve
post-concussion cognitive function and symptoms such as attention, concentration,
impulsivity, and fatigue.  This retrospective study by Reddy, et al. examined
the influence of amantadine on the improvement of cognitive deficits among 25
patients (11 male and 14 females, ~16 years old) who suffered a concussion and
had no persistent symptoms. All 25 patients sustained a concussion and had
persistent symptoms (defined as symptoms lasting at least 21 days) and/or
persistent deficits on the ImPACT neurocognitive battery.  Treatment consisted of 100 mg of amantadine
twice daily (at breakfast and lunch) for an average of 3 to 4 weeks.  This treatment group was compared to an age-,
sex-, and concussion history–matched group of 25 adolescents in the control or
“rest” group. Patients were excluded from the study if they had a history of
migraines, headaches, neurological disorders, sleep disorders, the diagnosis of
major psychiatric disorders, ADD/ADHD, or current/history of substance
abuse.  Patients were also excluded if
they were concurrently receiving medication that modified central nervous
system function or if they had a contraindication to amantadine.  The outcome measurement for the study was
pre- and post-intervention (i.e. administration of amantadine) ImPACT score of
verbal and visual memory, visual processing speed, reaction time, and symptom
scores of the amantadine group compared with the matched controls. Results
showed that over the study course both groups improved with time.  However, the rate of improvement in three
domains:  symptom recovery, verbal
memory, and reaction time was greater in the amantadine treated group than the
usual care “rest” group. There were no significant differences in visual memory
or visual motor processing speed.

The results of this study are noteworthy because it is
one of the first studies to suggest that amantadine may be effective in
improving symptom recovery for patients who are suffering from protracted
symptoms and have functional deficits evaluated with neurocognitive testing by
ImPACT.  The results add to a small but
increasing body of evidence that some pharmacological therapies may be useful
in concussion and traumatic brain injury management.  As with all retrospective chart review
research, the results of this study should be viewed as promising but
preliminary.  It was not a randomized
trial and the control group would have been more ideally a group of concussed
athletes treated with a placebo.  The
results should also be viewed with caution due to the small sample size of each
study group as well as the fact that rest, which is considered one of the most
important aspects of concussion recovery, could not be controlled for with
measures of adherence.  Furthermore, it
is difficult to fully determine from the results if additional time alone could
have been responsible for recovery and improvement of ImPACT testing.  Given their results, the authors advocate for
further study of amantadine in a double-blind placebo-controlled fashion.  Have you had experience with amantadine as a
recovery agent in post-concussion management? 
Do you feel that any other therapies, modalities, or medications are
helpful in managing the recovery of patients with prolonged post-concussion

Written by: Stephen Stache, MD and Marc I. Harwood, MD
Reviewed by: Jeffrey Driban

SMR Note: SMR does not traditionally provide posts for
retrospective studies but since the use of pharmacological interventions in
concussion management represents a potentially important emerging area of
research we felt it important to share. Please keep in mind that retrospective
case-control studies are not the same level of evidence as a randomized
clinical trial.

Related Readings:

Related Posts:

Reddy CC, Collins M, Lovell M, & Kontos AP (2012). Efficacy of Amantadine Treatment on Symptoms and Neurocognitive Performance Among Adolescents Following Sports-Related Concussion. The Journal of Head Trauma Rehabilitation PMID: 22613947