• Neuropsychiatric Inventory Irritability Domain [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  

• Neuropsychiatric Inventory Aggression Domain [ Time Frame: 28 days and 60 days ] [ Designated as safety issue: No ]
  
• State Anger Aggression Expression Inventory -- II [ Time Frame: 28 and 60 days ] [ Designated as safety issue: No ]
  
• Neuropsychiatric Inventory Irritability Domain [ Time Frame: 60 days ] [ Designated as safety issue: No ]
  
• Neuropsychiatric Inventory Caregiver Distress Score for Irritability and Aggression Domains [ Time Frame: 28 and 60 days ] [ Designated as safety issue: No ]
  
• Clinical Global Impressions [ Time Frame: 28 and 60 days ] [ Designated as safety issue: No ]
  
• Global Impression of Change [ Time Frame: 28 and 60 days ] [ Designated as safety issue: No ]
  
• Short Form-12 [ Time Frame: 28 and 60 days ] [ Designated as safety issue: No ]
  
• Glasgow Coma Scale - Extended [ Time Frame: 28 and 60 days ] [ Designated as safety issue: No ]
  
• Satisfaction With Life Scale [ Time Frame: 28 and 60 days ] [ Designated as safety issue: No ]
  
• Patient Health Questionnaire - 9 [ Time Frame: 28 and 60 days ] [ Designated as safety issue: No ]
  
• Beck Depression Inventory II [ Time Frame: 28 and 60 days ] [ Designated as safety issue: No ]
  
• Fatigue Impact Scale [ Time Frame: 28 and 60 days ] [ Designated as safety issue: No ]
  
• Family Assessment Device General Functioning Scale [ Time Frame: 28 and 60 days ] [ Designated as safety issue: No ]
  
• Neuropsychologic tests [ Time Frame: 28 and 60 days ] [ Designated as safety issue: No ]
  

PURPOSE OF PROJECT: To study the effect of amantadine 100 mg administered twice daily compared to placebo on irritability from baseline to treatment Day 28.

SUMMARY OF PROJECT: It is anticipated that 168 subjects with 168 corresponding subject informants will be recruited for the study. Carolinas Rehabilitation, the lead center, and 5 collaborating centers will enroll approximately 28 subjects each.

Subjects will be recruited primarily from the clinics. Also, letters will be sent to patients in our data base. If the first encounter with research personnel is by telephone, the research assistant will obtain verbal (telephone) consent from the subject's informant for the Neuropsychiatric Inventory (NPI) for subject irritability. The score on this questionnaire must be ≥ 6 for qualification. This allows pre-screening to take place and avoid an unnecessary clinic visit.

Subjects who consent and qualify will be randomized in a 1:1 ratio, amantadine to placebo. Stratification to randomization group will occur based on the presence of depression defined by a Beck's Depression Inventory-II (BDI-II) score ≥ 13. Randomized subjects will receive amantadine or placebo 100 mg twice daily every morning and 12 Noon. There will be 4 clinic visits. Visits will occur at baseline, for consenting and screening, day 28, day 60 and day 90. At all 4 clinic visits, both the subject and the informant will be given questionnaires regarding the subject's behavior and mood. Follow up phone calls will occur each week that the subject is not seen in the clinic until the end of the study. Follow up phone calls will assess for study medication compliance, adverse events and concomitant medication changes. Day 60 ends the period of the Randomized Clinical Trial phase of the study and the subjects will begin the 1 month continuation phase of the study when all participants receive active amantadine.

The following questionnaires will be used as measures of irritability for the subject and the informant: Neuropsychiatric Inventory (NPI), State Trait Anger Expression Inventory (STAXI-2), and Global Impression of Change.

The following questionnaires will be dispensed to the subject only: Short Form -12, Satisfaction With Life Scale, Patient Health Questionnaire, Beck Depression Inventory, Brief Symptom Inventory, Family Assessment Device, Fatigue Impact Scale, and tests of cognitive function. The Glasgow Outcome Score-Extended will be completed by the research assistant using information obtained primarily from the informant.

The Investigator will complete the Clinical Global Impression of change at Visits 1, 2, 3, and 4.

History and Physical Exam, creatinine level (kidney function) will be obtained for safety and tolerability. Serum pregnancy tests will be drawn at screening for females of childbearing potential.