title: Change in agitation in Alzheimer's disease in the placebo arm of a nine-week controlled trial.
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.
authors: Psychiatry and Behavioral Sciences,Division of Geriatric Psychiatry and Neuropsychiatry,Johns Hopkins School of Medicine,Johns Hopkins Bayview Medical Center,Baltimore,Maryland,USA.
authors: Paul B
authors: PB
authors: Rosenberg
authors: Department of Epidemiology,Johns Hopkins Bloomberg School of Public Health,Maryland,USA.
authors: Lea T
authors: LT
authors: Drye
authors: Alzheimer's Disease Care,Research and Education Program (AD-CARE),University of Rochester School of Medicine and Dentistry,Rochester,New York,USA.
authors: Anton P
authors: AP
authors: Porsteinsson
authors: Campbell Institute,CAMH,University of Toronto,Toronto,Ontario,Canada.
authors: Bruce G
authors: BG
authors: Pollock
authors: Psychiatry and Neurology,Division of Geriatric Psychiatry,College of Physicians and Surgeons,Columbia University,New York,USA.
authors: D P
authors: DP
authors: Devanand
authors: Department of Biostatistics,Johns Hopkins Bloomberg School of Public Health,Baltimore,Maryland,USA.
authors: Constantine
authors: C
authors: Frangakis
authors: Psychiatry and Neurology,Hotchkiss Brain Institute,University of Calgary,Calgary,Alberta,Canada.
authors: Zahinoor
authors: Z
authors: Ismail
authors: Psychiatry and Behavioral Sciences,Division of Geriatric Psychiatry and Neuropsychiatry,Johns Hopkins School of Medicine,Johns Hopkins Bayview Medical Center,Baltimore,Maryland,USA.
authors: Christopher
authors: C
authors: Marano
authors: Epidemiology and Biostatistics,Johns Hopkins Bloomberg School of Public Health,Baltimore,Maryland,USA.
authors: Curtis L
authors: CL
authors: Meinert
authors: Clinical Biotechnology Research Institute,Roper St. Francis Healthcare,Charleston,South Carolina,USA.
authors: Jacobo E
authors: JE
authors: Mintzer
authors: Department of Psychiatry and Behavioral Sciences,Department of Neurology,Johns Hopkins Bayview and Johns Hopkins School of Medicine,Baltimore,Maryland,USA.
authors: Cynthia A
authors: CA
authors: Munro
authors: Psychiatry and Neurology,Division of Geriatric Psychiatry,College of Physicians and Surgeons,Columbia University,New York,USA.
authors: Gregory
authors: G
authors: Pelton
authors: Psychiatry and Behavioral Sciences Johns Hopkins School of Medicine,Johns Hopkins Hospital,Baltimore,Maryland,USA.
authors: Peter V
authors: PV
authors: Rabins
authors: Psychiatry,Neurology,and Gerontology,Keck School of Medicine,University of Southern California,Los Angeles,California,USA.
authors: Lon S
authors: LS
authors: Schneider
authors: Departments of Medicine (Pulmonary) and Epidemiology (Center for Clinical Trials),Johns Hopkins Bloomberg School of Public Health,Baltimore,Maryland,USA.
authors: David M
authors: DM
authors: Shade
authors: 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.
authors: Daniel
authors: D
authors: Weintraub
authors: Clinical Science,Culture and Mental Health Lab,University of Southern California,Los Angeles,California,USA.
authors: Jeffery
authors: J
authors: Newell
authors: Aging Clinical Research Center,Director Mental Illness Research Education and Clinical Center,VA Palo Alto Health Care System,Virginia,USA.
authors: Jerome
authors: J
authors: Yesavage
authors: Psychiatry and Behavioral Sciences,Division of Geriatric Psychiatry and Neuropsychiatry,Johns Hopkins School of Medicine,Johns Hopkins Bayview Medical Center,Baltimore,Maryland,USA.
authors: Constantine G
authors: CG
authors: Lyketsos
mesh_terms: D000203:Activities of Daily Living; D000368:Aged; D000369:Aged, 80 and over; D000374:Aggression / Q000187:drug effects*; D000544:Alzheimer Disease / Q000523:psychology*; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D017028:Caregivers / Q000523:psychology; D015283:Citalopram / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D015990:Placebo Effect; D011569:Psychiatric Status Rating Scales; D011595:Psychomotor Agitation / Q000188:drug therapy*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram
keywords: Alzheimer’s disease; agitation; neuropsychiatric symptoms; randomized clinical trial