Compound Amantadine May Help Recovery and Irritability for Those with Traumatic Brain Injury

Compound Amantadine May Help Recovery and Irritability for Those with Traumatic Brain Injury

i-bottleIf you’re wondering where you heard about amantadine recently, you may be thinking of actor Michael J. Fox’s public announcements in recent years that he began using amantadine as part of his Parkinson’s Disease treatment regimen, as an off-label prescription to address his dyskinesia and complications from levodopa therapy. The actor was even able to return to network television after adding amantadine to his pharmacotherapy regimen, and now compound amantadine could prove a breakthrough active pharmaceutical ingredient for another class of patients—sufferers of traumatic brain injury (TBI).1

It’s hard to imagine what it’s like to undergo the devastating short- and long-term consequences of traumatic brain injury. In many ways, we feel that what happens in our brains is what makes up our “self,” and diseases or conditions that contribute to loss of brain function control can be both physically and emotionally difficult to experience and witness. For people 15 to 30 years old, it’s even the number one cause of death and disability, according to the Centers for Disease Control and Prevention.2

For pharmacists with patients who have received traumatic brain injury, even those who may be in semi-vegetative states, progressive research into compound amantadine treatments may signal breakthroughs in neuropharmacologic therapies.

Compound Amantadine for Patients in Semi-Vegetative States

Amantadine is an antiviral most commonly known as a treatment for Type A influenza, also known as avian flu or “bird flu.” The compound acts by inhibiting viral assembly during the process of replication, specifically against A subtypes, as it has no visible effect against B-strain viruses.3

In the years since Michael J. Fox’s announcement of his use of the drug, amantadine hydrochloride has become a common off-label treatment for a group of side effects known as “parkinsonian side effects,” which can occur from Parkinson’s disease, but also as side effects from antipsychotic medications. As an antidyskinetic medicine, it can be used to treat palsy and improve muscle control. This is thought to be a result of its effects on dopamine neurons and as a limited N-methyl-D-aspartate (NMDA) receptor agonist.4

Researchers who took note of the compound’s effects as an antidyskinetic posited that it might also improve function and lessen irritability in patients with TBI. The first double-blind studies were conducted in the late 1990s, and although they showed some promise for amantadine’s ability to promote recovery for patients suffering from traumatic consciousness disorders, they suffered from inadequate sample sizes and methodological issues that prevented any breakthroughs from the results.

A later 2012 study published in the New England Journal of Medicine sought to address the earlier studies’ shortcomings and covered 11 clinical sites in three countries, including patients ranging in age from 16 to 65 years old, and with a larger sample size of 184 patients and a clearer methodological framework. The study measured patients’ scores on the Disability Rating Scale (DRS) before and after treatment with compound amantadine, or with a placebo for the control group.

Pharmacists who worked in neuropharmacology found the researchers’ results highly intriguing. Although both the placebo-controlled group and the group taking doses of amantadine exhibited significant improvement in DRS scores during the 4-week trial, the amantadine group recovered at a much faster rate and required fewer dosage escalations during the trial period. A higher number of patients in the amantadine-dosage group displayed favorable outcomes at the end of the trial over the control group, meaning that their DRS benchmarks had improved at a statistically significant rate, from vegetative to semi-conscious or semi-conscious to minimally conscious, for instance.5

Treating Traumatic Brain Injury and Related Irritability with Amantadine

A more recent 2015 study published in the Journal of Neurotrauma sought to expand upon amantadine’s uses for neuropharmacology, exploring whether the compound might not only improve DRS scores, but also reduce symptoms of irritability among TBI patients. Examining 168 patients who had sustained acute TBI more than 6 months prior to the 60-day trial period, the double-blind study used several metrics to measure irritability change for patients, including scores on the Neuropsychiatric Inventory (NPI-I) from patients and observers, and the physician rating scale Clinical Global Impressions (CGI).

Conducted at seven sites across the U.S., the study examined chronic irritability, which was estimated to be present in 30 to 70 percent of patients with TBI in the post-acute period and severely affecting patients’ ability to recover, as well as a patient’s network of caregivers and medical professionals.

The study results showed that both the control and amantadine-dosed groups showed improvement at the 60-day mark, though patients and observers reported that the amantadine group showed more improvement. Neither group had any issues with adverse events, and ultimately, the study concluded that they could not say definitively whether amantadine improved irritability based on the data. However, the researchers also noted, and pharmacists would surely agree, that further research should be conducted because observers and patients themselves reported improvement at 60 days on the 100 mg twice daily amantadine dose.6

What’s Next for Studies into Compound Amantadine for TBI?

Amantadine is still primarily used as a treatment for parkinsonian side effects today. All studies into amantadine usage for traumatic brain injury have suffered from sample sizes too small for sweeping changes in pharmacotherapy for neurological trauma. As with any potentially promising area of research into possibly life-changing treatment methods for patients, pharmacists who work regularly with TBI patients need to pay close attention to any new information coming out regarding amantadine for TBI purposes.

Even though no large-scale studies are currently planned for investigating the use of amantadine to improve recovery or reduce irritability in TBI patients, compound pharmacists can still educate their patients and other specialists on the trauma care team about the potential efficacy of amantadine for individual patients. Off-label amantadine and amantadine hydrochloride compounded treatments may still be beneficial for certain patients, or as one addition to a treatment regimen.

Breakthroughs don’t occur overnight. Compounds do not become common treatments for specific conditions without rigorous research and a willingness from some pharmacists, physicians and patients to work together and try new treatments, just like Michael J. Fox’s work with amantadine for Parkinson’s treatment.

Pharmaceutica North America is a premier provider of high-quality bulk active pharmaceutical ingredients, unit-dose APIs and custom compounding kits, including kits and APIs for treating chronic and acute pain. Contact us to learn more about how our products can help you provide the best possible patient care.

Show 6 footnotes

  1. “It’s Official: Michael J. Fox Has a New Show! (So Is He on a New Drug?)” Aug. 22, 2012,
  2. “Placebo-Controlled Trial of Amantadine for Severe Traumatic Brain Injury,” March 1, 2012,
  3. “Amantadine,” accessed Jan. 24, 2016,
  4. “Amantadine,” accessed Jan. 24, 2016,
  5. “Placebo-Controlled Trial of Amantadine for Severe Traumatic Brain Injury,” Ibid.
  6. “Amantadine Effect on Perceptions of Irritability after Traumatic Brain Injury: Results of the Amantadine Irritability Multisite Study,” July 29, 2015,

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