Citalopram for Agitation in Alzheimer's Disease

This study is designed to examine the efficacy and safety of citalopram as treatment for
clinically significant agitation in Alzheimer's dementia (AD) patients. It will also
investigate pharmacogenomic, genetic, and clinical predictors of response to citalopram
therapy. The management of agitation is a major priority in treating patients with AD.
Non-pharmacologic options have limited effectiveness. Several pharmacologic options have
been explored, but findings for anticonvulsants, antipsychotics, and cholinesterase
inhibitors are disappointing or associated with questionable risk-benefit ratio. Better
pharmacologic options are needed. Selective serotonin reuptake inhibitors (SSRIs) show
promise as a treatment for agitation in AD, based on evidence of a link between agitation
and brain serotonin system abnormalities in AD patients, and on preliminary clinical data
from a single-site, randomized controlled trial (RCT) in which citalopram was superior to
perphenazine and placebo.

Inclusion Criteria

- Probable Alzheimer's disease (NINCDS-ADRDA criteria), with MMSE score of 5-28
inclusive

- A medication for agitation is appropriate, in the opinion of the study physician

- Clinically significant agitation for which either

1. the frequency of agitation as assessed by the NPI is 'Very frequently', or

2. the frequency of agitation as assessed by the NPI is 'Frequently' AND the
severity of the agitation as assessed by the NPI is 'Moderate', or 'Marked'

- Provision of informed consent for the participation in the study by patient or
surrogate (if necessary) and caregiver

- Availability of primary caregiver, who spends several hours a week with the patient
and supervises his/her care, to accompany the patient to study visits and to
participate in the study

- No change to AD medication within the month preceding randomization, including
starting, stopping, or dosage modifications

Exclusion criteria

- Meets criteria for Major Depressive Episode by DSM-IV (TR) criteria

- Presence of a brain disease that might otherwise explain the presence of dementia,
such as extensive brain vascular disease, Parkinson's disease, dementia with Lewy
bodies, traumatic brain injury, or multiple sclerosis

- Psychosis (delusions or hallucinations) requiring antipsychotic treatment in the
opinion of the study physician

- Treatment with citalopram is contraindicated in the opinion of the study physician

- Failure of past treatment with citalopram for agitation after adequate trial at a
minimally accepted dose (≥20 mg/day)

- Treatment with a medication that would prohibit the safe concurrent use of
citalopram, such as MAO inhibitors

- Need for acute psychiatric hospitalization or suicidal

- Current participation in a clinical trial or in any study that may add a significant
burden or affect neuropsychological or other study outcomes

- Current treatment with antipsychotics, anticonvulsants (other than dilantin), other
antidepressants (other than trazodone, ≤50 mg/day at bedtime), benzodiazepines (other
than lorazepam), or psychostimulants

- Any condition that, in the opinion of the study physician, makes it medically
inappropriate or risky for the patient to enroll in the trial