Research Reports - Effectiveness of amantadine in the reduction of chronic traumatic brain injury irritability and aggression

J Head Trauma Rehabil. 2013 Nov 20

Hammond FM, Bickett AK, Norton JH, Pershad R

BACKGROUND:: Following traumatic brain injury (TBI), individuals may experience
chronic problems with irritability or aggression, which may need treatment to
minimize the negative impact on their relationships, home life, social
interactions, community participation, and employment.
OBJECTIVE:: To test the a priori hypothesis that amantadine reduces irritability
(primary hypothesis) and aggression (secondary hypothesis) among individuals
greater than 6 months post-TBI.
METHODS:: A total of 76 individuals greater than 6 months post-TBI referred for
irritability management were enrolled in a parallel-group, randomized,
double-blind, placebo-controlled trial of amantadine (n = 38) versus placebo (n =
38). Study participants were randomly assigned to receive amantadine
hydrochloride 100 mg twice daily versus equivalent placebo for 28 days. Symptoms
of irritability and aggression were measured before and after treatment using the
Neuropsychiatric Inventory Irritability (NPI-I) and Aggression (NPI-A) domains,
as well as the NPI-Distress for these domains.
RESULTS:: In the amantadine group, 80.56% improved at least 3 points on the
NPI-I, compared with 44.44% in the group that received placebo (P = .0016). Mean
change in NPI-I was -4.3 in the amantadine group and -2.6 in the placebo group (P
= .0085). When excluding individuals with minimal to no baseline aggression, mean
change in NPI-A was -4.56 in the amantadine group and -2.46 in the placebo group
(P = .046). Mean changes in NPI-I and NPI-A Distress were not statistically
significant between the amantadine and placebo groups. Adverse event occurrence
did not differ between the 2 groups.
CONCLUSIONS:: Amantadine 100 mg every morning and at noon appears an effective
and safe means of reducing frequency and severity of irritability and aggression
among individuals with TBI and sufficient creatinine clearance.

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