Hammond et al.

(2018)

United States

RCT

PEDro= 9

N=119

Population: Mean age=38.6yr; Mean time post-injury=6.2yr; Injury severity: GCS<13.

Intervention: Individuals were allocated to receive either the placebo or 100mg amantadine twice a day for 60 days. Assessments were completed at baseline, day 28, and day 60.

Outcomes: Digit-span from Wechsler Memory Scale-III (DS), Trail Making Test (TMT), Controlled Oral Word Association Test (COWAT), Learning/Memory Index (LMI), Attention/Processing Speed Index (APSI).

1.        No significant differences were seen on the DS, TMT, COWAT, or the APSI between groups at any time point.

2.        The treatment group had significantly lower LMI scores at day 28 compared to the control group (p=0.001), this effect was not present at 60-day follow-up.

3.        The treatment group had significantly lower scores on the GCI compared to the control group at day 28 (p=0.002), this effect was not present at day 60 follow-up.

Schneider et al.

(1999)

USA

RCT

PEDro=5

N=10

Population: TBI; Mean Age=31 yr; Gender: Male=7, Female=3; GCS Score Range=3-11.

Intervention: Patients randomized to either amantadine (50-150 mg 2x/d) or placebo for 2 wk in a crossover design with a 2 wk 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 6 wk.

1.        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).

Kraus et al.

(2005)

USA

Pre-Post

N=22

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.

Intervention: 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).