Hammond et al.

(2015)

USA

RCT

PEDro=10

N_Initial=168, N_Final=157

Population: TBI=168; Amantadine (n=82): Mean Age=40.2 yr; Gender: Male=66, Female=16; Severity: Mild=20, Moderate=3, Severe=59. Placebo (n=86): Mean Age=38.2 yr; Gender: Male=64, Female=22; Severity: Mild=22, Moderate=1, Severe=63.

Intervention: Participants were randomized to receive either 100 mg of amantadine or a placebo every morning and at 12pm for 60 days. Assessments to determine state of irritability were conducted at baseline, 28 days, and 60 days.

Outcome Measure: Neuropsychiatric Inventory Irritability (NPI-I) Most Problematic, NPI-I Most Aberrant, NPI-I Distress.

1.        No significant differences in irritability between groups on observer NPI-I ratings at 28 days or 60 days, but both groups showed improvement in irritability.

2.        Participant-rated NPI-I Most Problematic (p=.0353) and Distress (p=.0362) scores were significantly different between amantadine and placebo at 60 days, however after adjustment multiple comparisons revealed no significant difference.

Hammond et al.

(2014)

USA

RCT

PEDro=9

N_Initial=76, N_Final=72

Population: TBI=76; Amantadine Group (n=38): Mean Age=34.7 yr; Gender: Male=25, Female=13; Mean Time Post Injury=5.3 yr; Mean GCS=9.5. Placebo Group (n=38): Mean Age=42.1 yr; Gender: Male=22, Female=16; Mean Time Post Injury=4.7 yr; Mean GCS=7.5.

Intervention: Participants were randomized to receive placebo or 100 mg of amantadine hydrochloride in the morning and at 12pm every day for 28 days. Participants were assessed for effects of amantadine on irritability and aggression at baseline and post-treatment.

Outcome Measure: Neuropsychiatric Inventory (NPI) Irritability (NPI-I) and 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.        81% of patients with a TBI  who took amantadine had improved irritability by at least 3 points on NPI-I, compared to 44% of placebo (p=.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 on NPI-D, BDI-II, GMHS, or BSI-anxiety.

4.        Only individuals with moderate to severe aggression at baseline on NPI-A had significant change in aggression after amantadine treatment compared to placebo (p=.046).