AAN 2011: Amantadine Improves Consciousness in TBI Patients with Disorders of Consciousness

Daily amantadine improves consciousness and increases function in patients with impaired consciousness following traumatic brain injury, according to a study presented at the 63rd Annual Meeting of the American Academy of Neurology.

Patients receiving amantadine improved in both clinical signs of increased consciousness and functional behaviors over 4 weeks of treatment, compared to those receiving placebo. The study was the first large-scale placebo-controlled trial of any medication for this condition.

“There have been no proven therapies for treatment of consciousness disturbances following traumatic brain injury,” said lead researcher Douglas Katz, MD, Associate Professor of Neurology at Boston University School of Medicine.

This absence of clinical trials is despite the fact that TBI is a highly prevalent and frequent disorder, with over 1.7 million Americans sustaining a brain injury each year. While most patients eventually recover, about 14% of patients are discharged from the hospital in a vegetative or minimally conscious state. Patients in a vegetative state have some eye opening and sleep-wake cycle activity, while those in a minimally conscious state engage in visual tracking, and inconsistent response to commands.

“While off-label medication use is common, there have been no proven therapies to promote recovery,” Katz said.

Previous case series and a small pilot trial indicated the potential of amantadine, a flu medication also used in Parkinson's disease. Amantadine is an NMDA antagonist and dopamine agonist, which may be related to its clinical efficacy in TBI, according to Katz.

To formally test the ability of amantadine to improve consciousness, Katz and colleagues enrolled 184 patients at 8 centers who were either in a vegetative or minimally conscious state. Eligible patients were between 4 and 16 weeks post-injury, were unable to follow commands reliably, and had no previous exposure to amantadine.

Patients received 100 mg twice daily for 4 weeks, followed by a 2-week washout. The primary outcome measures were change in slope on the Disability Rating Scale (DRS) and the Coma Recovery Scale-Revised (CRS-R). The DRS rates functional activities, while the CRS-R measures clinical correlates of recovery, such as increased arousal.

One hundred eighty-one patients completed the study. Patients receiving amantadine had a significantly steeper slope (faster recovery) on both scales compared to placebo. During washout, treated patients continued to improve, but at a slower rate.

“Eighteen percent of patients in the amantadine group remained in the vegetative state at the end of treatment, versus thirty-one percent of those in the placebo group,” Katz said.

There was no significant different in adverse events between the two groups.

“Amantadine is safe and effective in promoting more rapid functional recovery in patients with disorders of consciousness after traumatic brain injury,” Katz said. “It is the first proven therapy to promote recovery in TBI, and should be considered in patients with disorders of consciousness lasting more than four weeks.”