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Updated: Feb 23, 2026
Controlled Cortical Impact Model for Traumatic Brain Injury
Published on: August 5, 2014
Potential Impact of Amantadine on Aggression in Chronic Traumatic Brain Injury
Flora M Hammond1, James F Malec, Ross D Zafonte
1Indiana University School of Medicine, Indianapolis, Indiana (Drs Hammond, Malec, and Perkins and Ms Moser); Rehabilitation Hospital of Indiana, Indianapolis, Indiana (Drs Hammond and Malec); Spaulding Rehabilitation Hospital, Harvard Medical School, Massachusetts General Hospital, and Brigham and Women's Hospital, Boston, Massachusetts (Dr Zafonte); TIRR Memorial Hermann, Houston, Texas (Dr Sherer); Department of Physical Medicine and Rehabilitation, The Ohio State University, Columbus, Ohio (Dr Bogner); University of Washington, Seattle, Washington (Drs Dikmen and Bell); Department of Physical Medicine and Rehabilitation, Carolinas Rehabilitation, Carolinas HealthCare System, Charlotte, North Carolina (Ms Whitney); and University of Texas Southwestern Medical School, Dallas, Texas (Dr Bell).
Amantadine may reduce aggression in chronic traumatic brain injury (TBI) patients, according to participant reports. However, the drug did not significantly impact anger levels in this study.
Area of Science:
- Neuroscience
- Psychiatry
- Clinical Trials
Background:
- Chronic traumatic brain injury (TBI) can lead to persistent aggression and anger.
- Effective pharmacological interventions for aggression post-TBI are limited.
- Amantadine is being investigated for its potential neuropsychiatric effects.
Purpose of the Study:
- To evaluate the efficacy of amantadine in reducing anger and aggression in individuals with chronic TBI.
- To compare amantadine's effects against a placebo in a randomized, double-blind trial.
Main Methods:
- A randomized, double-blind, placebo-controlled trial involving 118 participants with chronic TBI and moderate-to-severe aggression.
- Participants received amantadine 100 mg twice daily or a placebo for 60 days.
- Anger and aggression were assessed using the State-Trait Anger Expression Inventory-2 (STAXI-2) and Neuropsychiatric Inventory-Agitation/Aggression (NPI-A) scores.
Main Results:
- Participant-rated NPI-A scores for Most Problematic and Distress showed statistically significant improvement with amantadine.
- No significant differences in STAXI-2 scores were observed between the amantadine and placebo groups after multiple comparisons adjustment.
- Both groups showed improvement, with 70% on amantadine and 56% on placebo showing improvement in observer-rated NPI-A.
Conclusions:
- Amantadine (100 mg twice daily) may be beneficial in decreasing aggression in individuals with chronic TBI, as reported by participants.
- The study found no significant impact of amantadine on anger.
- Further research may explore amantadine's role in managing specific behavioral disturbances after TBI.
