Effect of Amantadine on Executive Functioning Following Brain Injury

Author/Year/ Country/Study design/PEDro/ N





Kraus et al. (2005)

Population: TBI; Mean Age=36yr; Gender: Male=17, Female=5; Severity of Injury: Mild=6, Moderate=6, Severe=10; Mean Time Post Injury=63.2mo.
Treatment: Positron emission tomography (PET) scan was done and participants received amantadine (100mg titrated to up to 400mg/d over 3wk).  Amantadine was administered 3×/d (200mg at 8AM, 100mg at 12PM, and 100mg at 4PM) for 12wk.
Outcome Measure: Trail Making Test part A and B (TMT A, TMT B), Controlled Oral Word Association Test (COWAT), Digit Span, California Verbal Learning Test (CVLT), Rey Osterreith Complex Figure-immediate (Rey Im) and delayed (Rey De) recall.

  1. Measures of executive function, as indicated by TMT B and COWAT, were significantly improved in patients following treatment with amantadine (t=-2.47; p<0.02).
  2. No significant differences were found for attention (TMT A and Digit Span) or memory (CVLT, Rey Im, and Rey De).
  3. Correlational analyses with PET scan results suggest that there may be a strong relationship between executive domain improvement and changes in left pre-frontal metabolism (r=0.92; p=0.01) and left medial temporal metabolism (r=0.91; p=0.01).

Schneider et al. (1999)

Population: TBI; Mean Age=31yr; Gender: Male=7, Female=3; GCS Score Range=3-11.
Treatment: Patients randomized to either amantadine (50-150mg 2x/d) or placebo for 2wk in a crossover design with a 2wk washout period.
Outcome Measure: Battery of Neuropsychological tests, Neurobehavioural Rating Scale.

  1. There was a general trend towards improvement in the study sample over the 6wk.
  2. There were no significant between group differences in terms of orientation (p=0.062), attention (p=0.325), memory (p=0.341), executive flexibility (p=0.732) or behaviour (p=0.737).

PEDro = Physiotherapy Evidence Database rating scale score (Moseley et al., 2002).