Research Reports - Potential impact of amantadine on aggression in chronic traumatic brain injury

J Head Trauma Rehabil. 2017 Sep/Oct;32(5):308-318. doi:

Hammond FM(1), Malec JF, Zafonte RD, Sherer M, Bogner J, Dikmen S, Whitney MP,
Bell KR, Perkins SM, Moser EA.

OBJECTIVE: To assess the effects of amantadine on anger and aggression among
individuals with a chronic traumatic brain injury (TBI).
METHODS: A cohort of 118 persons with chronic TBI (>6 months postinjury) and
moderate-severe aggression selected from a larger cohort of 168 participants
enrolled in a parallel-group, randomized, double-blind, placebo-controlled trial
of amantadine 100 mg twice daily (n = 82) versus placebo (n = 86) for treatment
of irritability were studied. Anger and aggression were measured at treatment
days 0, 28, and 60 using observer-rated and participant-rated State-Trait Anger
Expression Inventory-2 (STAXI-2) and Neuropsychiatric
Inventory-Agitation/Aggression domain (NPI-A) Most Problematic and Distress
RESULTS: Participant-rated day 60 NPI-A Most Problematic (adjusted P = .0118) and
NPI-A Distress (adjusted P = .0118) were statistically significant between the 2
groups, but STAXI-2 differences were not significant after adjustment for
multiple comparisons. Substantial improvements were noted in both amantadine and
placebo groups (70% vs 56% improving at least 3 points on day 60 Observer NPI-A;
P = .11).
CONCLUSION: Amantadine 100 mg twice daily in this population with chronic TBI
appears to be beneficial in decreasing aggression from the perspective of the
individual with TBI. No beneficial impact on anger was found. 

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