Hammond et al.

(2015)

USA

RCT

PEDro=10

N_Initial=168, N_Final=157

Population: TBI. Amantadine Group (n=82): Mean Age=40.2yr; Gender: Male=66, Female=16; Severity: Mild=20, Moderate=3, Severe=59. Placebo Group (n=86): Mean Age=38.2yr; Gender: Male=64, Female=22; Severity: Mild=22, Moderate=1, Severe=63.

Intervention: Participants were randomized to receive either placebo or 100 mg of amantadine 2x/day for 60 days. Assessments were conducted at baseline, 28 days, and 60 days.

Outcome Measure: Neuropsychiatric Inventory Irritability (NPI-I).

1.        Observer-rated NPI-I scores showed no significant differences between groups at 28d or 60d, but both groups showed improvement in irritability.

2.        Participant-rated NPI-I Most Problematic (p=0.0353) and Distress (p=0.0362) scores were significantly different between amantadine and placebo at 60d, but there was no significant difference after adjustment for multiple comparisons.

Hammond et al.

(2014)

USA

RCT

PEDro=9

N_Initial=76, N_Final=72

Population: TBI. Amantadine Group (n=38): Mean Age=34.7yr; Gender: Male=25, Female=13; Mean Time Post Injury=5.3yr; Mean GCS=9.5. Placebo Group (n=38): Mean Age=42.1yr; Gender: Male=22, Female=16; Mean Time Post Injury=4.7yr; Mean GCS=7.5.

Intervention: Participants were randomized to receive placebo or 100 mg of amantadine 2x/day for 28 days. Assessments were conducted at baseline and 28 days.

Outcome Measure: Neuropsychiatric Inventory (NPI) Irritability (NPI-I), NPI Agitation/ Aggression (NPI-A), NPI Distress (NPI-D), Beck Depression Inventory-II (BDI-II), Brief Symptom Inventory (BSI), Global Mental Health Scale (GMHS).

1.        Eighty-one percent of the amantadine group had improved irritability by at least 3 points on NPI-I, compared to 44% of placebo (p=0.0016).

2.        Significant difference in frequency and severity of irritability on NPI-I between amantadine and placebo groups (p=.0085).

3.        No significant differences between amantadine and placebo groups on NPI-D, BDI-II, BSI-Anxiety, or GMHS.

4.        Only individuals with moderate to severe aggression at baseline on NPI-A had significant reduction in aggression after amantadine treatment compared to placebo (p=0.046).