Citalopram for Agitation in Alzheimer's Disease (CitAD)

JHSPH Center for Clinical Trials

Status and phase

Completed

Phase 3

Conditions

Alzheimer's Disease

Agitation

Treatments

Drug: placebo

Drug: citalopram

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00898807

R01AG031348 (U.S. NIH Grant/Contract)

IA0155

Details and patient eligibility

About

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

Full description

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.

Enrollment

186 patients

Sex

All

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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