Randomized Controlled Trial

. 2019 Nov;15(11):1427-1436.

doi: 10.1016/j.jalz.2019.06.4946. Epub 2019 Oct 3.

Escitalopram for agitation in Alzheimer's disease (S-CitAD): Methods and design of an investigator-initiated, randomized, controlled, multicenter clinical trial

Stephan Ehrhardt¹, Anton P Porsteinsson², Cynthia A Munro³, Paul B Rosenberg³, Bruce G Pollock⁴, Davangere P Devanand⁵, Jacobo Mintzer⁶, Tarek K Rajji⁴, Zahinoor Ismail⁷, Lon S Schneider⁸, Sheriza N Baksh⁹, Lea T Drye⁹, Dimitri Avramopoulos¹⁰, David M Shade⁹, Constantine G Lyketsos³; S-CitAD Research Group

Collaborators, Affiliations

Collaborators

S-CitAD Research Group:
Constantine G Lyketsos, Anton P Porsteinsson, Dimitri Avramopoulos, Cynthia Munro, Hochang Lee, Nicholas Bienko, Dave Shade, Stephan Ehrhardt, Jennifer Jones, Anne Shanklin Casper, Constantine Frangakis, Andy Lears, Sheriza Baksh, Jamie Perin, Laurie Ryan, Alvin D McKelvy, Paul Rosenberg, Milap Nowrangi, Sarah Lawrence, Meghan Schultz, Nimra Jamil, D P Devanand, Laura Simon-Pearson, Gregory Pelton Jacobo Mintzer, Olga Brawman-Mintzer, Arthur Williams, Anthony Awkar, Anton P Porsteinsson, Melanie Keltz, Nancy Kowalski, Kaitlyn Lane, Kim Martin, Susan Salem-Spencer, Asa Widman, Bruce G Pollock, Sanjeev Kumar, Lillian Lourenco, Benoit H Mulsant, Kyle Lago, Tarek K Rajji, Lon S Schneider, Maurcio Becerra, Karen Dagerman, Sonia Pawluczyk, Liberty Teodoro

Affiliations

¹ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. Electronic address: sehrhar6@jhu.edu.
² Department of Psychiatry, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
³ Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine and Johns Hopkins Bayview Medical Center, Baltimore, MD, USA.
⁴ Campbell Family Research Institute and Division of Adult Neurodevelopment and Geriatric Psychiatry, CAMH, Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
⁵ Division of Geriatric Psychiatry, New York State Psychiatric Institute and College of Physicians and Surgeons of Columbia University, New York, NY, USA.
⁶ Roper St. Francis Research and Innovation Center, Charleston, SC, USA; Medical University of South Carolina, College of Health Professionals and Ralph H Johnson VA Medical Center, Charleston, SC, USA.
⁷ Department of Psychiatry, Hotchkiss Brain Institute and O'Brien Institute for Public Health, University of Calgary, Calgary, AB, Canada; Department of Clinical Neurosciences, Hotchkiss Brain Institute and O'Brien Institute for Public Health, University of Calgary, Calgary, AB, Canada; Department of Community Health Sciences, Hotchkiss Brain Institute and O'Brien Institute for Public Health, University of Calgary, Calgary, AB, Canada.
⁸ Departments of Psychiatry and the Behavioral Sciences and Neurology, University of Southern California Keck School of Medicine and the University of Southern California Leonard Davis School of Gerontology, Los Angeles, CA, USA; Department of Neurology, University of Southern California Keck School of Medicine and the University of Southern California Leonard Davis School of Gerontology, Los Angeles, CA, USA.
⁹ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
¹⁰ Department of Psychiatry and Behavioral Sciences, Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

PMID: 31587995
PMCID: PMC6889953
DOI: 10.1016/j.jalz.2019.06.4946

Randomized Controlled Trial

Escitalopram for agitation in Alzheimer's disease (S-CitAD): Methods and design of an investigator-initiated, randomized, controlled, multicenter clinical trial

Stephan Ehrhardt et al. Alzheimers Dement. 2019 Nov.

. 2019 Nov;15(11):1427-1436.

doi: 10.1016/j.jalz.2019.06.4946. Epub 2019 Oct 3.

Authors

Collaborators

S-CitAD Research Group:
Constantine G Lyketsos, Anton P Porsteinsson, Dimitri Avramopoulos, Cynthia Munro, Hochang Lee, Nicholas Bienko, Dave Shade, Stephan Ehrhardt, Jennifer Jones, Anne Shanklin Casper, Constantine Frangakis, Andy Lears, Sheriza Baksh, Jamie Perin, Laurie Ryan, Alvin D McKelvy, Paul Rosenberg, Milap Nowrangi, Sarah Lawrence, Meghan Schultz, Nimra Jamil, D P Devanand, Laura Simon-Pearson, Gregory Pelton Jacobo Mintzer, Olga Brawman-Mintzer, Arthur Williams, Anthony Awkar, Anton P Porsteinsson, Melanie Keltz, Nancy Kowalski, Kaitlyn Lane, Kim Martin, Susan Salem-Spencer, Asa Widman, Bruce G Pollock, Sanjeev Kumar, Lillian Lourenco, Benoit H Mulsant, Kyle Lago, Tarek K Rajji, Lon S Schneider, Maurcio Becerra, Karen Dagerman, Sonia Pawluczyk, Liberty Teodoro

Affiliations

¹ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. Electronic address: sehrhar6@jhu.edu.
² Department of Psychiatry, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
³ Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine and Johns Hopkins Bayview Medical Center, Baltimore, MD, USA.
⁴ Campbell Family Research Institute and Division of Adult Neurodevelopment and Geriatric Psychiatry, CAMH, Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
⁵ Division of Geriatric Psychiatry, New York State Psychiatric Institute and College of Physicians and Surgeons of Columbia University, New York, NY, USA.
⁶ Roper St. Francis Research and Innovation Center, Charleston, SC, USA; Medical University of South Carolina, College of Health Professionals and Ralph H Johnson VA Medical Center, Charleston, SC, USA.
⁷ Department of Psychiatry, Hotchkiss Brain Institute and O'Brien Institute for Public Health, University of Calgary, Calgary, AB, Canada; Department of Clinical Neurosciences, Hotchkiss Brain Institute and O'Brien Institute for Public Health, University of Calgary, Calgary, AB, Canada; Department of Community Health Sciences, Hotchkiss Brain Institute and O'Brien Institute for Public Health, University of Calgary, Calgary, AB, Canada.
⁸ Departments of Psychiatry and the Behavioral Sciences and Neurology, University of Southern California Keck School of Medicine and the University of Southern California Leonard Davis School of Gerontology, Los Angeles, CA, USA; Department of Neurology, University of Southern California Keck School of Medicine and the University of Southern California Leonard Davis School of Gerontology, Los Angeles, CA, USA.
⁹ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
¹⁰ Department of Psychiatry and Behavioral Sciences, Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

PMID: 31587995
PMCID: PMC6889953
DOI: 10.1016/j.jalz.2019.06.4946

Abstract

Introduction: Alzheimer's disease (AD) is a disabling, common cause of dementia, and agitation is one of the most common and distressing symptoms for patients with AD. Escitalopram for agitation in Alzheimer's disease (S-CitAD) tests a novel, clinically derived therapeutic approach to treat agitation in patients with AD.

Methods: S-CitAD is a NIH-funded, investigator-initiated, randomized, multicenter clinical trial. Participants receive a structured psychosocial intervention (PSI) as standard of care. Participants without sufficient response to PSI are randomized to receive 15 mg escitalopram/day or a matching placebo in addition to PSI. Primary outcome is the Modified Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (mADCS-CGIC).

Discussion: S-CitAD will provide information about a practical, immediately available approach to treating agitation in patients with AD. S-CitAD may become a model of how to evaluate and predict treatment response in patients with AD and agitation as a neuropsychiatric symptom (ClinicalTrials.gov Identifier: NCT03108846).

Keywords: Agitation; Alzheimer dementia; Escitalopram; Neuropsychiatric symptoms; Psychosocial intervention; Randomized trial.

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Conflict of interest statement

Conflicts: DPD reports consulting for Eisai, Acadia, Avanir. LSS reports grants from NIA and the State of California, within 3 years and during the conduct of the study; grants from Eli Lilly, Merck, Novartis, Roche, Biogen, UCSD and personal fees from AC Immune, Allergan, Avraham, Axovant, Boehringer Ingelheim, Cognition, Lilly Merck, Neurim, Roche, Takeda, Toyama, and vTv outside the submitted work. TKR has received research support from Brain Canada, Brain and Behavior Research Foundation, BrightFocus Foundation, Canada Foundation for Innovation, Canada Research Chair, Canadian Institutes of Health Research, Centre for Aging and Brain Health Innovation, National Institutes of Health, Ontario Ministry of Health and Long-Term Care, Ontario Ministry of Research and Innovation, and the Weston Brain Institute. ZI has received funding from Brain Canada, Canadian Institutes of Health Research, and Canadian Consortium for Neurodegeneration and Aging. Consulting fees received from Allergan, Avanir, Janssen, Lilly, Lundbeck, Otsuka, Pfizer, Sunovion. PBR reports grants from NIA, Lilly, and Alzheimer’s Association within 3 years and during the conduct of the study; consulting fees from GLG, Otsuka, Avanir, Bionomics; travel support from Avanir and Otsuka. CGL reports grants from NIMH, NIA, Associated Jewish Federation of Baltimore, Weinberg Foundation, Forest, Glaxo-Smith-Kline, Eisai, Pfizer, Astra-Zeneca, Lilly, Ortho-McNeil, Bristol-Myers, Novartis, National Football League, Elan, Functional Neuromodulation, Bright Focus Foundation. Consultant fees received from Astra-Zeneca, Glaxo-Smith Kline, Eisai, Novartis, Forest, Supernus, Adlyfe, Takeda, Wyeth, Lundbeck, Merz, Lilly, Pfizer, Genentech, Elan, NFL Players Association, NFL Benefits Office, Avanir, Zinfandel, BMS, Abvie, Janssen, Orion, Otsuka, Servier, Astellas. Honorarium or travel support from Pfizer, Forest, Glaxo-Smith Kline, Health Monitor. JM reports consulting for ACADIA Pharmaceuticals and AVANIR Pharmaceuticals. APP reports personal fees from Acadia Pharmaceuticals, personal fees from Functional Neuromodulation, personal fees from Neurim Pharmaceuticals, personal fees from Grifols, personal fees from Eisai, personal fees from Toyama, personal fees from Biogen, personal fees from Lundbeck, personal fees from Merck, grants from AstraZeneca, grants from Avanir, grants from Eisai, grants from Biogen, grants from Eli Lilly, grants from Janssen, grants from Genentech/Roche, grants from Novartis, grants from Merck, grants from Transition Therapeutics, grants from Toyama, grants from NIA, grants from NIMH, grants from DOD, personal fees from Rockpointe, outside the submitted work. CAM, SNB, DMS, LTD, DA, and SE report no conflicts of interest.

Figures

**Figure 1:**
S-CitAD study design schematic

See this image and copyright information in PMC

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Escitalopram for agitation in Alzheimer's disease (S-CitAD): Methods and design of an investigator-initiated, randomized, controlled, multicenter clinical trial

Collaborators

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Escitalopram for agitation in Alzheimer's disease (S-CitAD): Methods and design of an investigator-initiated, randomized, controlled, multicenter clinical trial

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