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Change in agitation in Alzheimer's disease in the placebo arm of a nine-week controlled trial

Published online by Cambridge University Press:  25 August 2015

Paul B. Rosenberg
Affiliation:
Psychiatry and Behavioral Sciences, Division of Geriatric Psychiatry and Neuropsychiatry, Johns Hopkins School of Medicine, Johns Hopkins Bayview Medical Center, Baltimore, Maryland, USA
Lea T. Drye
Affiliation:
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Maryland, USA
Anton P. Porsteinsson
Affiliation:
Alzheimer's Disease Care, Research and Education Program (AD-CARE), University of Rochester School of Medicine and Dentistry, Rochester, New York, USA
Bruce G. Pollock
Affiliation:
Campbell Institute, CAMH, University of Toronto, Toronto, Ontario, Canada Campbell Family Mental Health Research Institute, Division of Geriatric Psychiatry, Faculty of Medicine University of Toronto, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
D.P. Devanand
Affiliation:
Psychiatry and Neurology, Division of Geriatric Psychiatry, College of Physicians and Surgeons, Columbia University, New York, USA
Constantine Frangakis
Affiliation:
Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Zahinoor Ismail
Affiliation:
Psychiatry and Neurology, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada Psychiatry, University of Toronto, Toronto, Ontario, Canada
Christopher Marano
Affiliation:
Psychiatry and Behavioral Sciences, Division of Geriatric Psychiatry and Neuropsychiatry, Johns Hopkins School of Medicine, Johns Hopkins Bayview Medical Center, Baltimore, Maryland, USA
Curtis L. Meinert
Affiliation:
Epidemiology and Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Jacobo E. Mintzer
Affiliation:
Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, Charleston, South Carolina, USA Department of Health Studies, Medical University of South Carolina, Charleston, South Carolina, USA Ralph H. Johnson VA Medical Center, Charleston, South Carolina, USA
Cynthia A. Munro
Affiliation:
Department of Psychiatry and Behavioral Sciences, Department of Neurology, Johns Hopkins Bayview and Johns Hopkins School of Medicine, Baltimore, Maryland, USA
Gregory Pelton
Affiliation:
Psychiatry and Neurology, Division of Geriatric Psychiatry, College of Physicians and Surgeons, Columbia University, New York, USA
Peter V. Rabins
Affiliation:
Psychiatry and Behavioral Sciences Johns Hopkins School of Medicine, Johns Hopkins Hospital, Baltimore, Maryland, USA
Lon S. Schneider
Affiliation:
Psychiatry, Neurology, and Gerontology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
David M. Shade
Affiliation:
Departments of Medicine (Pulmonary) and Epidemiology (Center for Clinical Trials), Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Daniel Weintraub
Affiliation:
Psychiatry and Neurology, Perelman School of Medicine at the University of Pennsylvania, Parkinson's Disease Research, Education and Clinical Center (PADRECC), Mental Illness Research, Education and Clinical Center (MIRECC), Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA
Jeffery Newell
Affiliation:
Clinical Science, Culture and Mental Health Lab, University of Southern California, Los Angeles, California, USA
Jerome Yesavage
Affiliation:
Aging Clinical Research Center, Director Mental Illness Research Education and Clinical Center, VA Palo Alto Health Care System, Virginia, USA Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California, USA
Constantine G. Lyketsos
Affiliation:
Psychiatry and Behavioral Sciences, Division of Geriatric Psychiatry and Neuropsychiatry, Johns Hopkins School of Medicine, Johns Hopkins Bayview Medical Center, Baltimore, Maryland, USA
Corresponding
E-mail address:

Abstract

Background:

Placebo responses raise significant challenges for the design of clinical trials. We report changes in agitation outcomes in the placebo arm of a recent trial of citalopram for agitation in Alzheimer's disease (CitAD).

Methods:

In the CitAD study, all participants and caregivers received a psychosocial intervention and 92 were assigned to placebo for nine weeks. Outcomes included Neurobehavioral Rating Scale agitation subscale (NBRS-A), modified AD Cooperative Study-Clinical Global Impression of Change (CGIC), Cohen-Mansfield Agitation Inventory (CMAI), the Neuropsychiatric Inventory (NPI) Agitation/Aggression domain (NPI A/A) and Total (NPI-Total) and ADLs. Continuous outcomes were analyzed with mixed-effects modeling and dichotomous outcomes with logistic regression.

Results:

Agitation outcomes improved over nine weeks: NBRS-A mean (SD) decreased from 7.8 (3.0) at baseline to 5.4 (3.2), CMAI from 28.7 (6.7) to 26.7 (7.4), NPI A/A from 8.0 (2.4) to 4.9 (3.8), and NPI-Total from 37.3 (17.7) to 28.4 (22.1). The proportion of CGI-C agitation responders ranged from 21 to 29% and was significantly different from zero. MMSE improved from 14.4 (6.9) to 15.7 (7.2) and ADLs similarly improved. Most of the improvement was observed by three weeks and was sustained through nine weeks. The major predictor of improvement in each agitation measure was a higher baseline score in that measure.

Conclusions:

We observed significant placebo response which may be due to regression to the mean, response to a psychosocial intervention, natural course of symptoms, or nonspecific benefits of participation in a trial.

Type
Research Article
Copyright
Copyright © International Psychogeriatric Association 2015 

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Supplementary material: File

Rosenberg supplementary material

Table S1

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Supplementary material: File

Rosenberg supplementary material

Table S2

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