Amantadine, an indirect dopamine agonist and N-methyl-D-aspartate antagonist was studied in a double-blind, placebo-controlled trial to determine its effectiveness in promoting recovery from a post-traumatic vegetative or minimally conscious state in human patients. Amantadine was administered for 4 weeks between 4 and 16 weeks after injury in patients with disorders of consciousness after traumatic brain injury. The authors found that amantadine significantly improved the rate of functional recovery over the 4-week period of treatment, when compared to recovery under placebo conditions. Improvements were seen in functionally meaningful behaviors such as consistent responses to commands, intelligible speech, reliable yes-or-no communication, and functional-object use. The authors hypothesize that the therapeutic effects of amantadine may reflect enhanced neurotransmission in the dopamine-dependent nigrostriatal, mesolimbic, and frontostriatal circuits that are responsible for mediating arousal, drive, and attention. The rate of recovery in the amantadine group slowed during the drug washout period, suggesting that the response is drug-dependent. According to the authors, whether amantadine treatment, when compared to placebo, improves long-term outcome or simply accelerates recovery en route to an equivalent level of function remains for future study.

Giacino JT, Whyte J, Bagiella E, Kalmar K, Childs N, et al.: Placelo-Controlled Trial of Amantadine for Severe Traumatic Brain Injury.  New England J. Medicine 366: 819-826 (2012).

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