Potential Impact of Amantadine on Aggression in Chronic Traumatic Brain Injury

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To assess the effects of amantadine on anger and aggression among individuals with a chronic traumatic brain injury (TBI).


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 scores.


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).


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.

Trial Registration:

clinicaltrials.gov Identifier: NCT00779324; http://www.clinicaltrials.gov/ct2/show/NCT00779324?term=irritability&rank=6.

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