The purpose of this study is to evaluate the safety and efficacy of citalopram for agitation in Alzheimer's dementia.

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 (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria), with Mini-Mental 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 Neuropsychiatric Inventory (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 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 Alzheimer's disease (AD) medications within the month preceding randomization, including starting, stopping, or dosage modifications

Exclusion criteria

• Meets criteria for Major Depressive Episode by Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (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
• Prolonged measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle (QT interval)
• 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 (greater than or equal to 20 mg/day)
• Treatment with a medication that would prohibit the safe concurrent use of citalopram, such as Monoamine oxidases (MAO) inhibitors
• Need for 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, less than or equal to 50 mg per 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

Adverse events (AEs) are collected systematically on the follow-up visit form; therefore, numbers of participants at risk for AEs reflect at least on follow-up visit form completed. Serious adverse events are often self-reported and can be collected any time throughout the study.