Patients with severe traumatic brain injury who were treated with amantadine hydrochloride (Symmetrel) had more rapid recovery of function than those receiving placebo, a multicenter randomized trial found.

During one month of treatment, improvements on the Disability Rating Scale (DRS) were faster in the active treatment group, with a difference in the slope of -0.24 points each week (P=0.007), according to Joseph T. Giacino, PhD, of Harvard Medical School, and colleagues.

The rapid recovery seen among patients receiving amantadine was manifest in “functionally meaningful behaviors such as consistent responses to commands, intelligible speech, reliable yes-or-no communication, and functional-object use,” the researchers observed in the March 1 issue of the New England Journal of Medicine.

However, once treatment was stopped, the placebo-treated patients had more rapid improvement compared with those who had received amantadine, and improvements among patients in both groups were similar by the end of the study.

Amantadine - originally marketed as a treatment for influenza and also used to treat Parkinson’s disease - is thought to act in brain injury patients by enhancing dopaminergic activity in various areas of the brain that mediate attention and arousal.

Although the precise neural mechanisms of action are uncertain, a pilot study suggested cognitive benefits among patients treated with the drug.

To further establish the safety and efficacy in patients with severe brain injury, Giacino and colleagues enrolled 184 patients who were either in a vegetative or minimally conscious state.

The active treatment began with doses of 100 mg twice daily for two weeks, then increased to 150 mg twice daily for the third week, and to 200 mg twice daily if needed during the fourth week.

Patients were assessed weekly through week six on the DRS, which has scores from 0 to 29, with higher scores reflecting worse status.

At baseline, levels of disability were similar in the active treatment and placebo groups, but after four weeks of treatment, severity was less in patients receiving amantadine:

- Moderately severe to severe disability (DRS scores 7 to 13), 25.6% for the amantadine group versus 16.8% for the placebo group
- Severe to extremely severe (DRS scores 14 to 21), 55.8% versus 51.6%
- Vegetative state to extremely vegetative (DRS scores 22 to 29), 18.6% versus 31.6%

Recovery was more rapid among those who were in a minimally conscious state than among those in a vegetative state, but the overall effect size on the DRS was similar (-0.24 points versus -0.25 points), the researchers reported.

And while faster recovery also was seen among those who began treatment earlier, the overall results were more pronounced in those treated later, with effect sizes of -0.40 points compared with -0.19 points.

During the two weeks after cessation of the active treatment, significant improvement continued in the placebo group, with a slope of -0.44 points each week (P<0.001).

Recovery at this time was slower, however, in the amantadine group, with a slope of -0.14, and by the end of week six, DRS scores were similar in the treatment and placebo groups.