The purpose of this clinical trial is to test whether or not the medication amantadine is
effective in reducing behavioral disturbances in patients with frontotemporal dementia.
Behavioral disturbances are a major cause of morbidity in frontotemporal dementia (FTD), yet
little is known about the effectiveness of medications to treat these disturbances.
Preliminary data suggests that the dopaminergic agent amantadine may reduce these
disturbances. This 6-week, prospective, randomized, placebo-controlled trial will compare
amantadine to placebo to assess its effectiveness in reducing behavioral symptoms.
- Frontotemporal dementia meeting diagnostic criteria of the Report of the Work Group on
Frontotemporal Dementia and Pick's Disease (McKhann et al, 2001). Diagnosis will be
established by clinical interview by a geriatric psychiatrist or neuropsychiatrist,
experienced with the diagnosis of FTD. Patients with the language presentation of FTD
will be enrolled if their behavioral disturbance meets the inclusion criteria. Use of
these diagnostic criteria would allow for enrollment of patients who in a clinical
setting carry the diagnosis of: semantic dementia, primary progressive aphasia,
cortical-basal degeneration, progressive supranuclear palsy, (amyotrophic lateral
sclerosis (ALS) with dementia, and Pick's disease, as all of these diagnoses are now
classified under the rubric of FTD.
- Frontal Behavioral Inventory (FBI) disinhibition subscale score of >16 (Kertesz et
al,1997; Kertesz et al 2000). Explanation of this subscale is found under outcome
- Men, women and minority groups will be included, ages 40-90 years old.
- Judged by the attending psychiatrist to be in sufficiently good health so as to be
treated using the study protocol in usual outpatient care circumstances.
- Patient, caregivers and or legal representatives provide informed consent for
participation in the study, using standard Johns Hopkins Division of Geriatric
Psychiatry and Neuropsychiatry procedures.
- Caregiver is available who spends at least 10 hours per week with the patient and is
able and willing to accompany the patient in the course of the study and to provide
- Presence of a brain disease that might otherwise fully explain the presence of
dementia or behavior disturbance, such as stroke, Parkinson's disease, traumatic brain
injury, multiple sclerosis, and the like.
- Treatment with amantadine is contraindicated in the opinion of the study attending
psychiatrist. Examples of this would be patients with advanced heart, liver or kidney
disease or a seizure disorder. Creatinine clearance >50mL/min will be required,
calculated using the Cockcroft-Gault equation.
- Failure of treatment with amantadine for behavior disturbance of FTD in the past.
- Treatment with a medication that would prohibit the safe concurrent use of amantadine.
- Ongoing regular alcohol use and an unwillingness to stop drinking alcohol during the
- Pregnancy or lactation.