• Alzheimer's Disease Cooperative Study-Clinical Global Impression Of Change (ADCS-CGIC), modified [ Time Frame: every 3 weeks over 9 weeks ] [ Designated as safety issue: No ]
• Neuropsychiatric Inventory (NPI) [ Time Frame: every 3 weeks over 9 weeks ] [ Designated as safety issue: No ]
• Udvalg for Kliniske Undersogelser (UKU) side effects rating scale [ Time Frame: every 3 weeks over 9 weeks ] [ Designated as safety issue: No ]

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.

• Alzheimer's Disease
• Agitation

• Drug: citalopram
• Drug: placebo

• Schneider LS, Tariot PN, Dagerman KS, Davis SM, Hsiao JK, Ismail MS, Lebowitz BD, Lyketsos CG, Ryan JM, Stroup TS, Sultzer DL, Weintraub D, Lieberman JA; CATIE-AD Study Group. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. N Engl J Med. 2006 Oct 12;355(15):1525-38.
• Steinberg M, Shao H, Zandi P, Lyketsos CG, Welsh-Bohmer KA, Norton MC, Breitner JC, Steffens DC, Tschanz JT; Cache County Investigators. Point and 5-year period prevalence of neuropsychiatric symptoms in dementia: the Cache County Study. Int J Geriatr Psychiatry. 2008 Feb;23(2):170-7.
• Pollock BG, Mulsant BH, Rosen J, Sweet RA, Mazumdar S, Bharucha A, Marin R, Jacob NJ, Huber KA, Kastango KB, Chew ML. Comparison of citalopram, perphenazine, and placebo for the acute treatment of psychosis and behavioral disturbances in hospitalized, demented patients. Am J Psychiatry. 2002 Mar;159(3):460-5.

Inclusion Criteria:

• Probable Alzheimer's disease (NINCDS-ADRDA criteria), with MMSE score of 5-26 inclusive
• Clinically significant agitation for which 1) a medication is needed; 2) score ≥ 4 on the Neuropsychiatric Inventory (NPI) agitation domain; 3) more than 2 agitated behaviors per week as assessed on the NPI
• 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
• Sufficient fluency, of the patient and caregiver, in written and spoken English or Spanish to participate in study visits, neuropsychological testing, and other outcome assessments
• Stable treatment for AD with cholinesterase inhibitors and/or memantine

Exclusion Criteria:

• Meets criteria for Major Depressive Episode by DSM-IV criteria
• Presence of a brain disease that might otherwise fully 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
• Failure of past treatment with citalopram for agitation after adequate trial at a minimally accepted dose (greater than or equal to 20mg/day)
• Treatment with a medication that would prohibit the safe concurrent use of citalopram, such as MAO inhibitors
• Need for psychiatric hospitalization, or acutely 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 antidepressants (other than trazodone, less than or equal to 50 mg per day at bedtime), benzodiazepines (other than lorazepam), or psychostimulants
• Any condition that makes it medically inappropriate or risky for the patient to enroll in the trial