This study is aimed at investigating specific pharmacological interventions in the treatment
of the disruptive, agitated behavior associated with Alzheimer's patients. In addition, it
is hoped that specific clinical profiles will be found to predict which treatment is most
effective for these particular patients.
Alzheimer's Disease (AD) is the most common cause of dementia, the fourth leading cause of
death, and has enormous economic and emotional costs for caregivers of patients. Most of
the patients with AD develop disruptive, agitated behaviors at some point during the ailment
that are a common catalyst for placement in long-term care settings where they represent
more than half of all the residents. Disruptive behaviors create stress for both staff and
patients in long-term care settings, reduce patient quality of life because of excess use of
physical restraints, and drain the financial resources of the facilities. This study
proposes to design specific interventions designed to decrease disruptive, agitated behavior
in patients with AD residing in long-term care facilities. This 12-week study will assess
the efficacy of two pharmacological agents, an atypical neuroleptic (risperidone) and an
anticonvulsant and mood stabilizer (gabapentin) while identifying moderators of differential
treatment response to the two drugs. Specifically, this study aims to randomize 130 patients
with AD who are manifesting agitated disruptive behavior, into two groups of 65 patients
each, with one group receiving risperidone and the other gabapentin. There are two main
hypotheses: 1) Patients in both of the treatment groups will manifest different overall
group decreases in ratings of disruptive, agitated behavior; and 2) Measurable, clinical
characteristics will identify subgroups of subjects with differential treatment response to
the two medications. The two variables to be considered as moderators are as follows: a)
Patients with higher psychosis ratings will manifest greater responsivity to risperidone
compared to gabapentin, and b) Patients with high levels of affective lability will manifest
greater responsivity to gabapentin compared to risperidone.
1. Diagnosis of probable AD according to DSM-IV, which show high agreement with
NINCDS-ADRDA criteria (McKhann et al., 1984); kappa = 0.81 (Chui et al., in press).
2. At least a two-week history of two or more agitated behaviors from the Agitation
Screening Inventory (a shortened version of the 24-item Revised Memory and Behavior
Problem Checklist) (RMBPC; Teri at al., 1992), occurring at least once weekly, and
rated by the caregiver or nursing staff as at least moderately distressing.
3. Not planning a change in living situation or placement during the investigational
4. Stability (of dose and type) of medications for nonexcluded concurrent medical
conditions (i.e. thyroid disease, anemia, cardiac disease) for four weeks prior to
5. Ability to ingest oral medications and participate in all scheduled evaluations.
6. A sixth grade education or a work history sufficient to exclude mental retardation.
7. 50 years of age or older.
8. Medically acceptable for experimental drugs as confirmed by physical evaluation and
9. Modified Hachinski Scale score of 4 or less.
1. Neurological diagnoses other than AD which affect cognitive function. These include
Parkinson?s Disease, tumors, hydrocephalus, history of significant trauma, and
2. A diagnosis of delirium by the Confusion Assessment Method (CAM, Inouye et al.,
3. A diagnosis of dementia related to infection with human immunodeficiency virus (HIV)
or amnestic disorder, as defined by DSM-IV.
4. Known hypersensitivity to risperidone or gabapentin.
5. Alcohol or drug abuse within the past year.
6. Serious, unstable medical illnesses (e.g., unstable angina, poorly controlled
diabetes mellitus, labile hypertension)
7. Any medical problem that would cause or exacerbate agitated behaviors (including
unstable thyroid dysfunction, electrolyte disturbances, urinary tract infection,
fecal impaction, respiratory disease complicated by hypoxia or hypercapnia, etc.)
8. Any psychotropic medications or other medications which may cause or exacerbate
agitated behavior. Patients taking these medications may participate in the study if
the drugs can be successfully discontinued during the washout period and the
remainder of the study, and if after discontinuation they still meet inclusion
criteria for the investigation. Excluded medications include: antipsychotics;
antidepressants; anxiolytics; CNS stimulants; anti convulsants; and sedative
9. Significantly abnormal laboratory findings.
10. Significantly abnormal EKG findings.
11. Conditions such as blindness, deafness, or other disability that may prevent the
patient from participating in the study.
12. Current participation in any other investigational drug study or treatment.