• Neuropsychiatric Inventory Irritability and Aggression(Caregiver distress scores) [ Time Frame: 28 days ] [ Designated as safety issue: No ]
• Neuropsychiatric Inventory Aggression Domain (frequency and severity) [ Time Frame: 28 days ] [ Designated as safety issue: No ]
• Global Impression of Change rated by clinician, individual with brain injury and caregiver [ Time Frame: 28 days ] [ Designated as safety issue: No ]

The purpose of this study is to determine if amantadine hydrochloride given 100 mg in the morning and at noon is safe and effective in the treatment of mood and behavior changes (i.e. irritability) after sustaining traumatic brain injury.

Amantadine hydrochloride is a drug used commonly in clinical practice at the Carolinas Rehabilitation for the treatment of mood and behavior changes following traumatic brain injury. Clinical observation suggests that the use of amantadine improves caregiver report of "irritability" though there are no studies to validate this observation. This study investigates the efficacy and side effect profile of amantadine hydrochloride given in 2 doses of 100 mgs each. Subjects are screened during regularly scheduled clinic appointments for the presence of irritability. If they are interested in possible participation in the study, they will be invited to meet with the research coordinator who will obtain informed consent. If the subject meets all the inclusion/exclusion requirements, they will leave clinic with study medication and begin taking the drug the next day. There will be a safety call between day 3 and 5 where the dose may be reduced to once per day. Follow-up assessment occurs at day 14 (by phone) and day 28 (in clinic). At study completion, the subject will have the opportunity to receive a prescription for amantadine as part of ongoing clinical care.

• Irritable Mood
• Aggression
• Traumatic Brain Injury

• Experimental: Amantadine 100 mg every morning and 12 noon
• Placebo Comparator: Placebo tablet every morning and 12 noon

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Inclusion Criteria:

• Closed head injury (defined as brain injury or impaired brain function resulting from externally inflicted trauma without penetrating injury) at least 6 months prior to enrollment.
• Age at time of enrollment: 16 - 65 inclusive (i.e., on or after 16th birthday, up to day before 66th birthday).
• Voluntary informed consent of patient and informant.
• Subject and informant willing to comply with the protocol, & are available for all scheduled clinic visits.
• Neuropsychiatric Inventory (NPI) Irritability Domain score > 2.
• Medically and neurologically stable during the month prior to enrollment.
• If taking antidepressant, anxiolytic, hypnotic, or stimulant medications, no change anticipated in these medications during the month prior to enrollment.
• No change in therapies or medications planned during the 28-day participation.
• No surgeries planned during the 28-day participation.
• Vision, hearing, speech, motor function, and comprehension must be sufficient for compliance with all testing procedures. Ability to interact and verbalize sufficient to participate in assessments.
• Informant (family member or close friend) who lives with the participant with daily interaction in order to observe occurrences of irritability.

Exclusion Criteria:

• Patients without a reliable informant
• Penetrating head injury
• Injury < 6 months prior to enrollment
• Inability to interact sufficient for communication with caregiver
• Acute and rehabilitation records unavailable or incomplete
• DSM-IV diagnosis of schizophrenia or psychosis
• Diagnosis of progressive or additional neurologic disease (such as, Alzheimer's disease, parkinson's disease, multi-infarct dementia, other cerebrovascular disorders with dementia, prior cerebrovascular accident, Huntington's disease, olivopontocerebellar atrophy, multisystem atrophy, multiple sclerosis, ALS, CNS tumor, progressive supranuclear palsy).
• Diagnosis of seizure in the month prior to enrollment.
• Previous allergy or adverse reaction to study drug
• Ingestion of amantadine hydrochloride during the month prior to enrollment.
• Concomitant use of neuroleptic agents or phenelzine
• Creatinine clearance <60
• Pregnancy (Beta-HCG performed on all females of child-bearing potential) and lactating females.
• Clinical signs of active infection