Sports Medicine Research: In the Lab & In the Field: Amantadine Shows Promise as Potential Post-Concussion Management Medication (Sports Med Res)
Friday, September 28, 2012

Amantadine Shows Promise as Potential Post-Concussion Management Medication

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

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 models of 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 symptoms?

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

5 comments:

samwalton said...

I have had an athlete who was seen by Dr. Collins from this research group and received the amantadine treatment. She was experiencing a lingering headache and sub-baseline results on the ImPACT at the time she was seen by him and after about 6-8 weeks of treatment with amantadine and some visual and vestibular therapy, she was able to become symptom free, her ImPACT scores improved and she was eventually able to return to play.
She was older than the subjects of this group (21y/o) but she improved nonetheless. I think that given this study and much anecdotal evidence, this may be a burgeoning research venture and perhaps eventually a "go-to" treatment for concussed individuals.

I agree that we need to see evidence in more randomized controlled trials before we get overly excited, but I'm optimistic. I think the future of concussion management is in more specific assessment, further understanding of the pathological changes that occur, and pharmacological interventions. The more we know about all of this, the better of our patients will be.

Stephen Stache said...

Thank you for your comment. Your story serves as appropriate example of the mentioned anecdotal evidence regarding the use of amantadine. I have heard some patients refer to a "light-switch" type feeling when they start the medication with regards to the symptoms of fogginess and ability to focus. In the sub-set of patients with lingering symptoms in the cognitive realm of post-concussion symptoms, amantadine seems very reasonable to consider.

Hopefully in the months to come more data will be published showing additional promise.

Kate said...

This is a very interesting finding since we still have very little understanding on concussions as well as post-concussion symptoms. It is hard to tell how an athlete will react to a concussion, with some bouncing right back and others suffering from symptoms for weeks to months. Due to this, athletic trainers need every tool possible to help treat every concussion scenario imaginable. This drug helping with post-concussive symptoms could be a great new tool. However, I definitely agree that it needs to be tested further before we rely upon it. For example, it should be tested on older populations. Health care professionals know that concussions affect younger populations differently compared to adults. Also I think it would be interesting to see how this drug physically affects the brain by imaging the brain of people who are taking the drug. Does this drug actually help the healing process of the brain or does it just mask the symptoms? We must be careful that we don't simply drug an athlete to decrease symptoms and send them back into participation before the brain has had an appropriate time to rest.

I have not used medications to treat post-concussive symptoms before. Normally I use relaxation tools to help decrease their headache which seems to be the root of most problems. For instance, they can't concentrate or have difficulty remembering because their head is constantly hurting. Therefore, I usually try to calm them down by giving them time each day in the doctors office to just relax on the exam table, then do gentle neck stretches. Just giving them an atmosphere that is calming and relaxing seems to help my patients most of the time.

Stephen Stache said...

Kate,

Thank you for your comments. I think it is important to remember that 85-90% of athletes who suffer a concussion will recover without any interventions other than brain rest. In clinical practice, pharmaceuticals are not recommended for use before 14 days post injury. Decision making for the use of pharmaceuticals should come from a trained medical professional with experience in concussion management and post-concussion syndrome. As you mentioned pharmaceuticals should never be used to mask symptoms to allow for return to play. In my clinical experience with concussion management which includes the use of pharmaceuticals, athletes are given medications with goal of symptom relief and return to normal function as a person and more importantly in the case of high school athletes, as a student. Most state legislation regarding concussion management now requires athletes to be symptom free and off all medications before return to play protocol is even a consideration.

Regarding you questions of how amantadine works on the brain in concussion recovery, I do not have an easy answer. Understanding pharmacokinetics and pharmacodynamics of medications that are used off-label is often difficult. As mentioned in the article and the blog post, amantadine is believed to modulate the transmission of dopamine. Based on findings in animal models and in the use of amantadine in patients with severe traumatic brain injury, the changes in the transmission of dopamine seems to improve symptoms related to cognitive function, attention and concentration. With this evidence in mind, amantadine has been used in concussion management to help with similar symptoms. This article serves as encouraging but not definitive evidence that with the desired additional research, the use of amantadine could become more accepted.

Anonymous said...

I am on Amantadine and 2 other medications for cluster migrains and migrains etc. I have been out for a couple weeks and to be honest it is kind of scary how much has changed without it. Mornings-afternoons simply hurt when I am atually able to get to the store if I remember my list I am still confused why and what am I geting? By afteernoon if things havent gone smoothly I am wipped and my day/night completly reversed. Food is somthing I make myself choke down when I happen to actally be hungry I take advantage and just eat whatever mostly peanut butter. My loss of apatight I can trace back to the amount of food that simply wont stay down when the pain is so bad. I am fairly sure this is not all related to being out of one pill for a few weeks if it is well there has to be another way. This is just hopfully the last of many head injurys for me it has kicked my butt for over a year now with no sighns of letting up. Call me a baby but I am tired of pain taking pills that manage to take the edge off and being tired.

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