Parkinson's drug Amantadine may help brain injury victims: Study

By Dr. Ananya Mandal, MDMar 1 2012

According to a new study Amantadine – a drug used to treat the symptoms of Parkinson's disease, also speeds recovery from severe traumatic brain injuries.

The study shows that Amantadine helps boost brain levels of dopamine, a neurotransmitter linked to arousal. And for patients who are in a vegetative state following a brain injury, the drug can help -- possibly by improving responsiveness during rehabilitation.

“There are clear benefits to getting patients from point A to point B faster and relieving some of those initial deficits more quickly,” said study author Joseph Giacino, director of rehabilitation neuropsychology at Boston's Spaulding Rehabilitation Hospital. “If you talk to a patient's family, you'll know what it means for them to be able to communicate sooner.”

For the study Giacino and colleagues followed 184 patients with “disorders of consciousness” following traumatic brain injuries sustained up to 16 weeks previously. Eighty-seven patients received amantadine for four weeks during their inpatient rehabilitation, while the rest received a placebo. Four weeks is typical for acute inpatient rehabilitation in the U.S.

After four weeks, more people in the flu drug group could give reliable yes-and-no answers, follow commands or use a spoon or hairbrush - things that few of them could do at the start. Far fewer patients who got amantadine remained in a vegetative state, 17 percent versus 32 percent.
“Over the four-week course of treatment, the amantadine group clearly outpaced the placebo group in terms of their rate of improvement,” said Giacino. When ranked in terms of disability, more patients treated with amantadine were less-disabled compared with patients who received a placebo. And fewer amantadine patients finished the four-week trial in a vegetative state.

Patients treated with amantadine were also more likely to rapidly regain “cognitively mediated behaviors that serve as the foundation for functional independence,” such as the ability to recognize objects, sustain attention and communicate. The study was published today in the New England Journal of Medicine.

However the advantages afforded by amantadine were not permanent. Two weeks after the treatment was stopped, the drug's benefits wore off – “more compelling evidence that this drug was in fact pushing the rate of recovery,” said Giacino. It's not known whether prolonged treatment would lead to more pronounced and sustained effects, he said.

Each year, an estimated 1.7 million Americans suffer a traumatic brain injury. Falls, car crashes, colliding with or getting hit by an object, and assaults are the leading causes. About three-quarters are concussions or other mild forms that heal over time. But about 52,000 people with brain injuries die each year and 275,000 are hospitalized, many with persistent, debilitating injuries, according to government figures.

With no proven remedies to rely on, doctors have used a variety of medicines approved for other ailments in the hopes that they would help brain injury patients. Those decisions are based on “hunches and logic rather than data,” said Dr. John Whyte, of the Moss Rehabilitation Research Institute in suburban Philadelphia. He led the study along with Giacino.

Giacino's study is the first to carefully compare the drug to a placebo. “Traumatic brain injury is tricky,” said Giacino. “We know that the majority of these individuals are going to get a lot better in the first three months after the injury, and it's very difficult to judge whether a person got better because you started a particular medication or whether the mechanism of injury was such that it allowed them to get better anyway.”

Because the drug is approved for Parkinson's disease, doctors can and do use it off-label for traumatic brain injury patients - a practice now supported by the study.

“What's so important about this study is that it really validated the agent's use in this population,” said Dr. Jaime Levine, director of brain injury rehabilitation at NYU Langone Medical Center's Rusk Institute of Rehabilitation Medicine. “I think these findings will improve awareness ... improve the quality of care, and access to care.”

Although the study did not uncover how amantadine helped to speed recovery, Levine said it likely “lowers the activation energy needed for a patient to start interacting with their environment.” “If someone isn't awake enough to learn or relearn things in rehab, they're unlikely to consolidate that learning,” she said. “Using amantadine early in the acute rehabilitation setting will allow a patient to benefit so much more from the rehab they're getting.”

The study also opens the door to test amantadine in patients with non-traumatic brain injuries from stroke, aneurysm, oxygen deprivation and tumor resection, Levine said. “All of these things can cause a disorder of consciousness oftentimes clinically indistinguishable from traumatic brain injury,” she said. “I hope this trial will pave the way for more work looking at amantadine in various conditions.”

Dr. Ramon Diaz-Arrastia said the results were welcome news in a field that has seen many failed efforts. He is director of clinical research at the government's Center for Neuroscience and Regenerative Medicine, which works with the military and government scientists on brain injury research. “It's an important step toward developing better therapies,” he said.