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The objective of the current study was to determine the efficacy of amantadine in improving cognitive and behavioural performance in a traumatic brain injury (TBI) rehabilitation sample. The design was a prospective, randomized, double-blind, placebo-controlled, crossover design. Subjects were 10 adult traumatic brain injury patients in an acute brain injury rehabilitation unit. Subjects received a 2-week trail of amantadine or placebo, followed by a 2-week washout, then a 2-week trail of the alternative (placebo or amantadine). Neuropsychological outcome measures included orientation, attention, executive function, memory, orientation, behaviour, and a composite variable. Results of repeated measures ANOVA and regression analysis of slope/change showed a main effect of time, but no significant difference for amantadine versus placebo. In conclusion, although patients generally improved, this initial exploratory study found no differences in rate of cognitive improvement between subjects given amantadine versus those given placebo. However, the small sample size, heterogeneous population, acute time course, and large number of dependent variables limit power and generalizability. Implications are discussed for further research to better answer questions regarding efficacy of amantadine post-TBI. [ABSTRACT FROM AUTHOR]