Citalopram for Agitation in Alzheimer's Disease

Official Title: “A Multi-Center Randomized Placebo-Controlled Clinical Trial Study of Citalopram for the Treatment of Agitation in Alzheimer's Disease”

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.

Intervention(s) in this Clinical Trial

• Drug: citalopram
  • target dose 30mg daily for 9 weeks
• Drug: placebo
  • daily for 9 weeks

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Citalopram
• Placebo Comparator: Placebo

Primary Measures

• NeuroBehavior Rating Scale
  • Time Frame: every 3 weeks over 9 weeks
    Safety Issue?: No
• CGIC
  • Time Frame: Every 3 weeks over 9 weeks
    Safety Issue?: No

Secondary Measures

• Cohen-Mansfield Agitation Inventory
  • Time Frame: every 3 weeks over 9 weeks
    Safety Issue?: Yes
• Neuropsychiatric Inventory (NPI)
  • Time Frame: every 3 weeks over 9 weeks
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Johns Hopkins University Other

Overall Clinical Trial Officials and Contacts

Constantine Lyketsos, MD, MHS Principal Investigator Johns Hopkins University  

Overall Contact: Anne Roche 410-550-9024 

Information obtained from ClinicalTrials.gov on February 02, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00898807

Study ID Number: IA0155

ClinicalTrials.gov Identifier: NCT00898807

Health Authority: United States: Institutional Review Board