Giacino et al. (2012)

USA

RCT

PEDro=7

N=184

Population: TBI; Amantadine Group (n=87): Mean Age=35.5 yr; Gender: Male=64, Female=23; Median Time Post Injury=48 days. Placebo Group (n=97): Mean Age=37.2 yr; Gender: Male=69, Female=28; Median Time Post Injury=47 days.

Intervention: Participants were randomized to receive either amantadine (100 mg, 2x/ days, 14 days. Dose increased to 150 mg 2x/ day at week 3, and to 200 mg 2x/ day at week 4 if DRS score had not improved by at least 2 points from baseline) or a placebo for 4 wk. Outcomes were assessed at baseline, 4 wk and 6 wk.

Outcome Measure: Disability Rating Scale (DRS).

1.         DRS scores improved significantly more in the amantadine group compared to the placebo group at 4 wk (p=0.007).

2.         Rate of improvement on DRS was significantly slowed from 4-6 wk (p=0.02).

3.         The overall improvement on DRS from baseline to 6 wk was not statistically different between groups (p>0.05).

Meythaler et al. (2002)

USA

RCT Crossover

PEDro=6

N=35

Population: TBI; Mean Age=31 yr; Gender: Male=26, Female=9; Time Post Injury<6 wk; Mean GCS=5.4.

Intervention: Patients received amantadine at 200 mg/ day (Group 1, n=15) or placebo (Group 2, n=20) for 6 wk, after which they received the alternate treatment for 6 wk.

Outcome Measures: Mini Mental Status Exam (MMSE), Disability Rating Scale (DRS), Functional Independence Measure-Cognitive (FIM-cog), Galveston Orientation and Amnesia Test (GOAT).

1.        In Group 1, there was a mean improvement in scores on MMSE (+14.3, p=0.0185), DRS (-9.8, p=0.0022), GOS (+0.8, p=0.0077), and FIM-cog (+15.1, p=0.0033) with amantadine.

2.        No improvements were observed in Group 1 with placebo administration (p>0.05).

3.        In Group 2, there was a mean improvement in scores on MMSE (+10.5, p=0.0015), DRS (-9.4, p=0.0006), GOS (+0.5, p=0.0231), and FIM-cog (+11.3, p=0.003) with placebo.

4.        Group 2 continued to make significant gains in mean scores for MMSE (+6.3, p=0.0409), DRS (-3.8, p=0.0099), and FIM-cog (+5.2, p=0.0173) with amantadine.

Hughes et al. (2005)

Canada

Case Control

N=123

Population: TBI; Amantadine Group (n=28): Mean Age=37.36 yr; Gender: Male=17, Female=11; Mean Time Post Injury=6 wk; Mean GCS=4.14. Control Group (n=95): Mean Age=38.76; Gender: Male=58, Female=37; Mean Time Post Injury=6 wk; Mean GCS=4.18.

Intervention: Patients were compared based on whether they received amantadine or not (control). Most patients received an initial dose of 100 mg 2×/ day that increased to 200 mg 2×/ day if there was no improvement. Treatment was discontinued 3wk after emergence from coma.

Outcome Measure: Emergence from coma.

1.        The proportion of patients emerging from coma between amantadine and control groups was similar (46% versus 38%, p=0.42).

2.        Survival analysis identified age (p=0.004), GCS (p=0.008), and somatosensory evoked potential (p=0.0002) to be significant predictors of time to emerge from coma.

3.        After controlling for these variables, amantadine did not significantly contribute to patient’s emergence from coma.

Saniova et al. (2004)

Slovakia

Case Control

N=74

Population: TBI; Amantadine Group (n=41): Mean Age=42.12 yr; Gender: Male=35, Female=6; Mean GCS=4.74. Control Group (n=33): Mean Age=43.91 yr; Gender: Male=30, Female=3; Mean GCS=4.70.

Intervention: Patients were compared based on whether they had received standard therapy and amantadine (200 mg, 2×/ day) or standard therapy alone (control).

Outcome Measures: Glasgow Coma Scale (GCS), Mortality.

1.        At discharge, patients treated with amantadine showed significantly higher GCS scores (9.76 versus 5.73, p<0.0001).

2.        At discharge, patients treated with amantadine had a significantly lower mortality rate (6.06% versus 51.51%, p<0.001) than controls.