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

Paul B Rosenberg¹, Lea T Drye², Anton P Porsteinsson³, Bruce G Pollock⁴, D P Devanand⁵, Constantine Frangakis⁶, Zahinoor Ismail⁷, Christopher Marano¹, Curtis L Meinert⁸, Jacobo E Mintzer⁹, Cynthia A Munro¹⁰, Gregory Pelton⁵, Peter V Rabins¹¹, Lon S Schneider¹², David M Shade¹³, Daniel Weintraub¹⁴, Jeffery Newell¹⁵, Jerome Yesavage¹⁶, Constantine G Lyketsos¹; CitAD Research Group

Affiliations

¹ Psychiatry and Behavioral Sciences,Division of Geriatric Psychiatry and Neuropsychiatry,Johns Hopkins School of Medicine,Johns Hopkins Bayview Medical Center,Baltimore,Maryland,USA.
² Department of Epidemiology,Johns Hopkins Bloomberg School of Public Health,Maryland,USA.
³ Alzheimer's Disease Care,Research and Education Program (AD-CARE),University of Rochester School of Medicine and Dentistry,Rochester,New York,USA.
⁴ Campbell Institute,CAMH,University of Toronto,Toronto,Ontario,Canada.
⁵ Psychiatry and Neurology,Division of Geriatric Psychiatry,College of Physicians and Surgeons,Columbia University,New York,USA.
⁶ Department of Biostatistics,Johns Hopkins Bloomberg School of Public Health,Baltimore,Maryland,USA.
⁷ Psychiatry and Neurology,Hotchkiss Brain Institute,University of Calgary,Calgary,Alberta,Canada.
⁸ Epidemiology and Biostatistics,Johns Hopkins Bloomberg School of Public Health,Baltimore,Maryland,USA.
⁹ Clinical Biotechnology Research Institute,Roper St. Francis Healthcare,Charleston,South Carolina,USA.
¹⁰ Department of Psychiatry and Behavioral Sciences,Department of Neurology,Johns Hopkins Bayview and Johns Hopkins School of Medicine,Baltimore,Maryland,USA.
¹¹ Psychiatry and Behavioral Sciences Johns Hopkins School of Medicine,Johns Hopkins Hospital,Baltimore,Maryland,USA.
¹² Psychiatry,Neurology,and Gerontology,Keck School of Medicine,University of Southern California,Los Angeles,California,USA.
¹³ Departments of Medicine (Pulmonary) and Epidemiology (Center for Clinical Trials),Johns Hopkins Bloomberg School of Public Health,Baltimore,Maryland,USA.
¹⁴ 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.
¹⁵ Clinical Science,Culture and Mental Health Lab,University of Southern California,Los Angeles,California,USA.
¹⁶ Aging Clinical Research Center,Director Mental Illness Research Education and Clinical Center,VA Palo Alto Health Care System,Virginia,USA.

PMID: 26305876
PMCID: PMC4669064
DOI: 10.1017/S1041610215001106

Randomized Controlled Trial

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

Paul B Rosenberg et al. Int Psychogeriatr. 2015 Dec.

. 2015 Dec;27(12):2059-67.

doi: 10.1017/S1041610215001106. Epub 2015 Aug 25.

Authors

Affiliations

¹ Psychiatry and Behavioral Sciences,Division of Geriatric Psychiatry and Neuropsychiatry,Johns Hopkins School of Medicine,Johns Hopkins Bayview Medical Center,Baltimore,Maryland,USA.
² Department of Epidemiology,Johns Hopkins Bloomberg School of Public Health,Maryland,USA.
³ Alzheimer's Disease Care,Research and Education Program (AD-CARE),University of Rochester School of Medicine and Dentistry,Rochester,New York,USA.
⁴ Campbell Institute,CAMH,University of Toronto,Toronto,Ontario,Canada.
⁵ Psychiatry and Neurology,Division of Geriatric Psychiatry,College of Physicians and Surgeons,Columbia University,New York,USA.
⁶ Department of Biostatistics,Johns Hopkins Bloomberg School of Public Health,Baltimore,Maryland,USA.
⁷ Psychiatry and Neurology,Hotchkiss Brain Institute,University of Calgary,Calgary,Alberta,Canada.
⁸ Epidemiology and Biostatistics,Johns Hopkins Bloomberg School of Public Health,Baltimore,Maryland,USA.
⁹ Clinical Biotechnology Research Institute,Roper St. Francis Healthcare,Charleston,South Carolina,USA.
¹⁰ Department of Psychiatry and Behavioral Sciences,Department of Neurology,Johns Hopkins Bayview and Johns Hopkins School of Medicine,Baltimore,Maryland,USA.
¹¹ Psychiatry and Behavioral Sciences Johns Hopkins School of Medicine,Johns Hopkins Hospital,Baltimore,Maryland,USA.
¹² Psychiatry,Neurology,and Gerontology,Keck School of Medicine,University of Southern California,Los Angeles,California,USA.
¹³ Departments of Medicine (Pulmonary) and Epidemiology (Center for Clinical Trials),Johns Hopkins Bloomberg School of Public Health,Baltimore,Maryland,USA.
¹⁴ 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.
¹⁵ Clinical Science,Culture and Mental Health Lab,University of Southern California,Los Angeles,California,USA.
¹⁶ Aging Clinical Research Center,Director Mental Illness Research Education and Clinical Center,VA Palo Alto Health Care System,Virginia,USA.

PMID: 26305876
PMCID: PMC4669064
DOI: 10.1017/S1041610215001106

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.

Keywords: Alzheimer’s disease; agitation; neuropsychiatric symptoms; randomized clinical trial.

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Conflict of interest statement

Conflict of Interest: None.

References

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

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

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