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Published Online: 1 April 2016

Effects of Citalopram on Neuropsychiatric Symptoms in Alzheimer’s Dementia: Evidence From the CitAD Study

Anne K. Leonpacher, M.D., Matthew E. Peters, M.D., Lea T. Drye, Ph.D., Kelly M. Makino, B.S., Jeffery A. Newell, B.A., D.P. Devanand, M.D., Constantine Frangakis, Ph.D., … Show All … , Cynthia A. Munro, Ph.D., Jacobo E. Mintzer, M.D., Bruce G. Pollock, M.D., Ph.D., Paul B. Rosenberg, M.D., Lon S. Schneider, M.D., David M. Shade, J.D., Daniel Weintraub, M.D., Jerome Yesavage, M.D., Constantine G. Lyketsos, M.D., M.H.S., and Anton P. Porsteinsson, M.D. for the CitAD Research GroupAuthors Info & Affiliations
Publication: American Journal of Psychiatry
Volume 173, Number 5
https://doi.org/10.1176/appi.ajp.2016.15020248
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Abstract

Objective:

Citalopram has been shown to improve agitation in patients with Alzheimer’s disease. The authors evaluated whether other neuropsychiatric symptoms improve with citalopram treatment compared with placebo.

Method:

In this planned secondary analysis of the Citalopram for Agitation in Alzheimer’s Disease study, the authors evaluated the effect of citalopram on the 12 neuropsychiatric symptom domains assessed by the Neuropsychiatric Inventory (NPI). They compared caregiver-reported NPI scores at week 9 in patients receiving citalopram (30 mg/day) or placebo with regard to both the presence or absence of individual neuropsychiatric symptoms and individual domain scores (reflecting severity) in participants who had symptoms at week 9.

Results:

At week 9, participants treated with citalopram were significantly less likely to be reported as showing delusions (odds ratio=0.40), anxiety (odds ratio=0.43), and irritability/lability (odds ratio=0.38). A comparison of median scores of participants with symptoms present at week 9 showed significant differences favoring citalopram for hallucinations and favoring placebo for sleep/nighttime behavior disorders.

Conclusions:

While dosage constraints must be considered because of citalopram’s adverse effect profile, this agent’s overall therapeutic effects in patients with Alzheimer’s disease and agitation, in addition to efficacy for agitation/aggression, included reductions in the frequency of irritability, anxiety, and delusions; among patients who had these symptoms at week 9, they included a reduction in the severity of hallucinations but an increase in the severity of sleep/nighttime behavior disorders.

Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Volume 173 • Number 5 • May 01, 2016
Pages: 473 - 480
PubMed: 27032628

History

Received: 24 February 2015
Revision received: 10 January 2016
Accepted: 26 January 2016
Published online: 1 April 2016
Published in print: May 01, 2016

Authors

Details

Anne K. Leonpacher, M.D.
From the Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore; the Johns Hopkins Bloomberg School of Public Health, Baltimore; the Alzheimer’s Disease Care, Research, and Education Program, University of Rochester School of Medicine and Dentistry, Rochester, N.Y.; the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford; the Division of Geriatric Psychiatry, Department of Psychiatry, New York State Psychiatric Institute and College of Physicians and Surgeons of Columbia University, New York; the Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, and the Department of Psychiatry, Ralph H. Johnson VA Medical Center, Charleston, S.C.; the Campbell Institute, Centre for Addiction and Mental Health, and the Department of Psychiatry, University of Toronto, Toronto; the Department of Psychiatry and Behavioral Sciences and the Department of Neurology, Keck School of Medicine of University of Southern California, Los Angeles; and the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
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Matthew E. Peters, M.D.
From the Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore; the Johns Hopkins Bloomberg School of Public Health, Baltimore; the Alzheimer’s Disease Care, Research, and Education Program, University of Rochester School of Medicine and Dentistry, Rochester, N.Y.; the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford; the Division of Geriatric Psychiatry, Department of Psychiatry, New York State Psychiatric Institute and College of Physicians and Surgeons of Columbia University, New York; the Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, and the Department of Psychiatry, Ralph H. Johnson VA Medical Center, Charleston, S.C.; the Campbell Institute, Centre for Addiction and Mental Health, and the Department of Psychiatry, University of Toronto, Toronto; the Department of Psychiatry and Behavioral Sciences and the Department of Neurology, Keck School of Medicine of University of Southern California, Los Angeles; and the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
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Lea T. Drye, Ph.D.
From the Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore; the Johns Hopkins Bloomberg School of Public Health, Baltimore; the Alzheimer’s Disease Care, Research, and Education Program, University of Rochester School of Medicine and Dentistry, Rochester, N.Y.; the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford; the Division of Geriatric Psychiatry, Department of Psychiatry, New York State Psychiatric Institute and College of Physicians and Surgeons of Columbia University, New York; the Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, and the Department of Psychiatry, Ralph H. Johnson VA Medical Center, Charleston, S.C.; the Campbell Institute, Centre for Addiction and Mental Health, and the Department of Psychiatry, University of Toronto, Toronto; the Department of Psychiatry and Behavioral Sciences and the Department of Neurology, Keck School of Medicine of University of Southern California, Los Angeles; and the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
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Kelly M. Makino, B.S.
From the Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore; the Johns Hopkins Bloomberg School of Public Health, Baltimore; the Alzheimer’s Disease Care, Research, and Education Program, University of Rochester School of Medicine and Dentistry, Rochester, N.Y.; the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford; the Division of Geriatric Psychiatry, Department of Psychiatry, New York State Psychiatric Institute and College of Physicians and Surgeons of Columbia University, New York; the Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, and the Department of Psychiatry, Ralph H. Johnson VA Medical Center, Charleston, S.C.; the Campbell Institute, Centre for Addiction and Mental Health, and the Department of Psychiatry, University of Toronto, Toronto; the Department of Psychiatry and Behavioral Sciences and the Department of Neurology, Keck School of Medicine of University of Southern California, Los Angeles; and the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
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Jeffery A. Newell, B.A.
From the Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore; the Johns Hopkins Bloomberg School of Public Health, Baltimore; the Alzheimer’s Disease Care, Research, and Education Program, University of Rochester School of Medicine and Dentistry, Rochester, N.Y.; the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford; the Division of Geriatric Psychiatry, Department of Psychiatry, New York State Psychiatric Institute and College of Physicians and Surgeons of Columbia University, New York; the Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, and the Department of Psychiatry, Ralph H. Johnson VA Medical Center, Charleston, S.C.; the Campbell Institute, Centre for Addiction and Mental Health, and the Department of Psychiatry, University of Toronto, Toronto; the Department of Psychiatry and Behavioral Sciences and the Department of Neurology, Keck School of Medicine of University of Southern California, Los Angeles; and the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
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D.P. Devanand, M.D.
From the Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore; the Johns Hopkins Bloomberg School of Public Health, Baltimore; the Alzheimer’s Disease Care, Research, and Education Program, University of Rochester School of Medicine and Dentistry, Rochester, N.Y.; the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford; the Division of Geriatric Psychiatry, Department of Psychiatry, New York State Psychiatric Institute and College of Physicians and Surgeons of Columbia University, New York; the Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, and the Department of Psychiatry, Ralph H. Johnson VA Medical Center, Charleston, S.C.; the Campbell Institute, Centre for Addiction and Mental Health, and the Department of Psychiatry, University of Toronto, Toronto; the Department of Psychiatry and Behavioral Sciences and the Department of Neurology, Keck School of Medicine of University of Southern California, Los Angeles; and the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
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Constantine Frangakis, Ph.D.
From the Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore; the Johns Hopkins Bloomberg School of Public Health, Baltimore; the Alzheimer’s Disease Care, Research, and Education Program, University of Rochester School of Medicine and Dentistry, Rochester, N.Y.; the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford; the Division of Geriatric Psychiatry, Department of Psychiatry, New York State Psychiatric Institute and College of Physicians and Surgeons of Columbia University, New York; the Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, and the Department of Psychiatry, Ralph H. Johnson VA Medical Center, Charleston, S.C.; the Campbell Institute, Centre for Addiction and Mental Health, and the Department of Psychiatry, University of Toronto, Toronto; the Department of Psychiatry and Behavioral Sciences and the Department of Neurology, Keck School of Medicine of University of Southern California, Los Angeles; and the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
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Cynthia A. Munro, Ph.D.
From the Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore; the Johns Hopkins Bloomberg School of Public Health, Baltimore; the Alzheimer’s Disease Care, Research, and Education Program, University of Rochester School of Medicine and Dentistry, Rochester, N.Y.; the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford; the Division of Geriatric Psychiatry, Department of Psychiatry, New York State Psychiatric Institute and College of Physicians and Surgeons of Columbia University, New York; the Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, and the Department of Psychiatry, Ralph H. Johnson VA Medical Center, Charleston, S.C.; the Campbell Institute, Centre for Addiction and Mental Health, and the Department of Psychiatry, University of Toronto, Toronto; the Department of Psychiatry and Behavioral Sciences and the Department of Neurology, Keck School of Medicine of University of Southern California, Los Angeles; and the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
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Jacobo E. Mintzer, M.D.
From the Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore; the Johns Hopkins Bloomberg School of Public Health, Baltimore; the Alzheimer’s Disease Care, Research, and Education Program, University of Rochester School of Medicine and Dentistry, Rochester, N.Y.; the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford; the Division of Geriatric Psychiatry, Department of Psychiatry, New York State Psychiatric Institute and College of Physicians and Surgeons of Columbia University, New York; the Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, and the Department of Psychiatry, Ralph H. Johnson VA Medical Center, Charleston, S.C.; the Campbell Institute, Centre for Addiction and Mental Health, and the Department of Psychiatry, University of Toronto, Toronto; the Department of Psychiatry and Behavioral Sciences and the Department of Neurology, Keck School of Medicine of University of Southern California, Los Angeles; and the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
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Bruce G. Pollock, M.D., Ph.D.
From the Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore; the Johns Hopkins Bloomberg School of Public Health, Baltimore; the Alzheimer’s Disease Care, Research, and Education Program, University of Rochester School of Medicine and Dentistry, Rochester, N.Y.; the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford; the Division of Geriatric Psychiatry, Department of Psychiatry, New York State Psychiatric Institute and College of Physicians and Surgeons of Columbia University, New York; the Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, and the Department of Psychiatry, Ralph H. Johnson VA Medical Center, Charleston, S.C.; the Campbell Institute, Centre for Addiction and Mental Health, and the Department of Psychiatry, University of Toronto, Toronto; the Department of Psychiatry and Behavioral Sciences and the Department of Neurology, Keck School of Medicine of University of Southern California, Los Angeles; and the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
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Paul B. Rosenberg, M.D.
From the Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore; the Johns Hopkins Bloomberg School of Public Health, Baltimore; the Alzheimer’s Disease Care, Research, and Education Program, University of Rochester School of Medicine and Dentistry, Rochester, N.Y.; the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford; the Division of Geriatric Psychiatry, Department of Psychiatry, New York State Psychiatric Institute and College of Physicians and Surgeons of Columbia University, New York; the Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, and the Department of Psychiatry, Ralph H. Johnson VA Medical Center, Charleston, S.C.; the Campbell Institute, Centre for Addiction and Mental Health, and the Department of Psychiatry, University of Toronto, Toronto; the Department of Psychiatry and Behavioral Sciences and the Department of Neurology, Keck School of Medicine of University of Southern California, Los Angeles; and the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
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Lon S. Schneider, M.D.
From the Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore; the Johns Hopkins Bloomberg School of Public Health, Baltimore; the Alzheimer’s Disease Care, Research, and Education Program, University of Rochester School of Medicine and Dentistry, Rochester, N.Y.; the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford; the Division of Geriatric Psychiatry, Department of Psychiatry, New York State Psychiatric Institute and College of Physicians and Surgeons of Columbia University, New York; the Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, and the Department of Psychiatry, Ralph H. Johnson VA Medical Center, Charleston, S.C.; the Campbell Institute, Centre for Addiction and Mental Health, and the Department of Psychiatry, University of Toronto, Toronto; the Department of Psychiatry and Behavioral Sciences and the Department of Neurology, Keck School of Medicine of University of Southern California, Los Angeles; and the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
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David M. Shade, J.D.
From the Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore; the Johns Hopkins Bloomberg School of Public Health, Baltimore; the Alzheimer’s Disease Care, Research, and Education Program, University of Rochester School of Medicine and Dentistry, Rochester, N.Y.; the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford; the Division of Geriatric Psychiatry, Department of Psychiatry, New York State Psychiatric Institute and College of Physicians and Surgeons of Columbia University, New York; the Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, and the Department of Psychiatry, Ralph H. Johnson VA Medical Center, Charleston, S.C.; the Campbell Institute, Centre for Addiction and Mental Health, and the Department of Psychiatry, University of Toronto, Toronto; the Department of Psychiatry and Behavioral Sciences and the Department of Neurology, Keck School of Medicine of University of Southern California, Los Angeles; and the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
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Daniel Weintraub, M.D.
From the Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore; the Johns Hopkins Bloomberg School of Public Health, Baltimore; the Alzheimer’s Disease Care, Research, and Education Program, University of Rochester School of Medicine and Dentistry, Rochester, N.Y.; the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford; the Division of Geriatric Psychiatry, Department of Psychiatry, New York State Psychiatric Institute and College of Physicians and Surgeons of Columbia University, New York; the Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, and the Department of Psychiatry, Ralph H. Johnson VA Medical Center, Charleston, S.C.; the Campbell Institute, Centre for Addiction and Mental Health, and the Department of Psychiatry, University of Toronto, Toronto; the Department of Psychiatry and Behavioral Sciences and the Department of Neurology, Keck School of Medicine of University of Southern California, Los Angeles; and the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
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Jerome Yesavage, M.D.
From the Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore; the Johns Hopkins Bloomberg School of Public Health, Baltimore; the Alzheimer’s Disease Care, Research, and Education Program, University of Rochester School of Medicine and Dentistry, Rochester, N.Y.; the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford; the Division of Geriatric Psychiatry, Department of Psychiatry, New York State Psychiatric Institute and College of Physicians and Surgeons of Columbia University, New York; the Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, and the Department of Psychiatry, Ralph H. Johnson VA Medical Center, Charleston, S.C.; the Campbell Institute, Centre for Addiction and Mental Health, and the Department of Psychiatry, University of Toronto, Toronto; the Department of Psychiatry and Behavioral Sciences and the Department of Neurology, Keck School of Medicine of University of Southern California, Los Angeles; and the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
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Constantine G. Lyketsos, M.D., M.H.S.
From the Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore; the Johns Hopkins Bloomberg School of Public Health, Baltimore; the Alzheimer’s Disease Care, Research, and Education Program, University of Rochester School of Medicine and Dentistry, Rochester, N.Y.; the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford; the Division of Geriatric Psychiatry, Department of Psychiatry, New York State Psychiatric Institute and College of Physicians and Surgeons of Columbia University, New York; the Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, and the Department of Psychiatry, Ralph H. Johnson VA Medical Center, Charleston, S.C.; the Campbell Institute, Centre for Addiction and Mental Health, and the Department of Psychiatry, University of Toronto, Toronto; the Department of Psychiatry and Behavioral Sciences and the Department of Neurology, Keck School of Medicine of University of Southern California, Los Angeles; and the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
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Anton P. Porsteinsson, M.D.
From the Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore; the Johns Hopkins Bloomberg School of Public Health, Baltimore; the Alzheimer’s Disease Care, Research, and Education Program, University of Rochester School of Medicine and Dentistry, Rochester, N.Y.; the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford; the Division of Geriatric Psychiatry, Department of Psychiatry, New York State Psychiatric Institute and College of Physicians and Surgeons of Columbia University, New York; the Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, and the Department of Psychiatry, Ralph H. Johnson VA Medical Center, Charleston, S.C.; the Campbell Institute, Centre for Addiction and Mental Health, and the Department of Psychiatry, University of Toronto, Toronto; the Department of Psychiatry and Behavioral Sciences and the Department of Neurology, Keck School of Medicine of University of Southern California, Los Angeles; and the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
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for the CitAD Research Group
From the Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore; the Johns Hopkins Bloomberg School of Public Health, Baltimore; the Alzheimer’s Disease Care, Research, and Education Program, University of Rochester School of Medicine and Dentistry, Rochester, N.Y.; the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford; the Division of Geriatric Psychiatry, Department of Psychiatry, New York State Psychiatric Institute and College of Physicians and Surgeons of Columbia University, New York; the Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, and the Department of Psychiatry, Ralph H. Johnson VA Medical Center, Charleston, S.C.; the Campbell Institute, Centre for Addiction and Mental Health, and the Department of Psychiatry, University of Toronto, Toronto; the Department of Psychiatry and Behavioral Sciences and the Department of Neurology, Keck School of Medicine of University of Southern California, Los Angeles; and the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
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Notes

Address correspondence to Dr. Porsteinsson ([email protected]).

Funding Information

National Institute of Mental Health10.13039/100000025: R01AG031348
National Institute on Aging10.13039/100000049: R01AG031348
Supported by National Institute on Aging (NIA) and NIMH grant R01AG031348, and in part by NIH grant P50-AG05142 (to University of Southern California and Dr. Schneider).

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