Agitation in Alzheimer's dementia (AD) is a significant public health problem with serious consequences for patients and caregivers. 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), understudied in this area, 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, placebo-controlled trial (RCT) in which citalopram was superior to perphenazine and placebo. A definitive RCT is now warranted investigating the efficacy and safety of an SSRI for agitation in AD. To carry out such a study, the proposed Citalopram for Agitation in AD (CITAD) will bring together investigators who have collaborated successfully in the ongoing Depression in Alzheimer's Disease Study (DIADS-2) and the completed Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE- AD). CITAD will examine the efficacy and safety of citalopram as treatment for clinically significant agitation in AD patients. It will also investigate pharmacogenomic, genetic, and clinical predictors of response to citalopram therapy. CITAD will be a placebo-controlled, masked, 9-week, 8-site RCT involving 200 patients with AD. It will enroll patients from real world outpatient, nursing home and assisted living settings. Using state of the art clinical ratings and novel weekly caregiver telephone ratings, CITAD will examine the effects of citalopram on agitation, other neuropsychiatric symptoms, cognition, quality of life, and daily functioning. CITAD will also conduct careful safety monitoring. This study is of great importance, as it will determine definitively the efficacy and safety of a promising SSRI as a treatment for agitation in AD, a condition with no treatment options that are both proven and without significant risk. Should citalopram be found effective, it will likely become a first line therapy, given the limitations of other pharmacologic options. CITAD will also provide significant knowledge about predictors of response, and lay the foundation for future studies to understand mechanisms involved in the effects of citalopram and other SSRIs on agitation. Agitation in Alzheimer's dementia (AD) is a significant public health problem with serious consequences for patients and caregivers. The management of agitation is a major priority in treating patients with AD. The proposed Citalopram for Agitation in AD (CITAD) will bring together investigators who have collaborated successfully in the ongoing Depression in Alzheimer's disease study (DIADS-2) and the completed Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD).

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG031348-05
Application #
8311701
Study Section
Special Emphasis Panel (ZAG1-ZIJ-7 (M1))
Program Officer
Ryan, Laurie M
Project Start
2008-09-15
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2014-08-31
Support Year
5
Fiscal Year
2012
Total Cost
$1,372,242
Indirect Cost
$283,072
Name
Johns Hopkins University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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Drye, Lea T; Spragg, David; Devanand, D P et al. (2014) Changes in QTc interval in the citalopram for agitation in Alzheimer's disease (CitAD) randomized trial. PLoS One 9:e98426
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