“Exposure to amantadine is associated with more rapid emergence of cognitively mediated behaviors that serve as the foundation for functional independence,” the authors comment. However, they found that the effect waned when treatment was discontinued.
Dr. Joseph T. Giacino, at Spaulding Rehabilitation Hospital in Boston, Massachusetts, and colleagues point out that amantadine is commonly prescribed for patients recovering from severe traumatic brain injury, but studies of its effects have been less than rigorous.
For the current trial, the team enrolled 184 patients in a vegetative of minimally conscious state 4-16 weeks after brain injury and randomized them to 4 weeks of placebo or amantadine at doses increasing from 100 mg to 200 twice daily. They were then followed for an additional 2 weeks.
The primary outcome was the rate of improvement in the Disability Rating Scale (DRS) during the 4 weeks of treatment. Both groups improved significantly over this period, but the decline (i.e., improvement) in DRS score was faster in the amantadine group (difference, -0.24 points/week; p=0.007).
In the subsequent 2-week period, however, the rate of improvement slowed in the amantadine group while it continued as before in the placebo group — such that at 6 weeks from baseline the improvement in DRS score was not significantly different in the two groups.
“Whether treatment with amantadine, as compared with placebo, improves the long-term outcome or simply accelerates recovery en route to an equivalent level of function remains unknown,” Dr. Giacino and colleagues comment.
Be that as it may, they add: “In view of health care cost constraints and declining lengths of stay for inpatient rehabilitation, amantadine-induced acceleration of recovery may represent an important advance.”
The New England Journal of Medicine, 2012;366:819-826.