title: Sedation mediates part of Citalopram's effect on agitation in Alzheimer's disease.
abstract: BACKGROUND
  We found a benefit of citalopram for agitation in the Citalopram for Agitation in Alzheimer's Disease study (CitAD), and wondered if this was mediated by a sedative effect. CitAD was a randomized, placebo-controlled, double-blind, parallel group trial conducted at 8 academic centers in the United States and Canada from August 2009 to January 2013. One hundred sixty-two participants with probable Alzheimer's disease (AD) and clinically significant agitation were analyzed in this study. Participants received a psychosocial intervention and were randomized to receive either citalopram or placebo (approximately half assigned to each group). Participants were rated on the Neurobehavioral Rating Scale Agitation subscale and measures of sedation (i.e., fatigue and somnolence).
  
  
  METHODS
  Using the MacArthur Foundation procedures for documenting a mediator effect, we performed a secondary analysis examining whether sedation mediates the effect of treatment on agitation outcome.
  
  
  RESULTS
  We found a statistically significant mediating effect of sedation on agitation outcomes, but the magnitude of the effect was small, only explaining 11% of the variance in agitation, with a significant, but modest effect size of 0.16 (95% CI: 0.08 to 0.22).
  
  
  CONCLUSIONS
  The benefit of citalopram was partly due to sedation but largely due to other mechanisms of action.
authors.affiliation: Department of Psychology, University of Southern California, Los Angeles, CA, 90089, United States.
authors.forename: Jeffery
authors.initials: J
authors.lastname: Newell
authors.affiliation: Department of Veterans Affairs Health Care System, Palo Alto, CA, 94304, United States; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, 94305-5717, United States; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, United States. Electronic address: yesavage@stanford.edu.
authors.forename: Jerome A
authors.initials: JA
authors.lastname: Yesavage
authors.affiliation: Department of Veterans Affairs Health Care System, Palo Alto, CA, 94304, United States; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, 94305-5717, United States.
authors.forename: Joy L
authors.initials: JL
authors.lastname: Taylor
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, 94305-5717, United States.
authors.forename: Helena C
authors.initials: HC
authors.lastname: Kraemer
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Bayview Medical Center and Johns Hopkins School of Medicine, Baltimore, MD, 21205, United States.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Munro
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, 94305-5717, United States.
authors.forename: Leah
authors.initials: L
authors.lastname: Friedman
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Bayview Medical Center and Johns Hopkins School of Medicine, Baltimore, MD, 21205, United States.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Rosenberg
authors.affiliation: Department of Veterans Affairs Health Care System, Palo Alto, CA, 94304, United States; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, 94305-5717, United States.
authors.forename: Michelle
authors.initials: M
authors.lastname: Madore
authors.affiliation: Department of Veterans Affairs Health Care System, Palo Alto, CA, 94304, United States; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, United States.
authors.forename: Steven Z
authors.initials: SZ
authors.lastname: Chao
authors.affiliation: Division of Geriatric Psychiatry, New York State Psychiatric Institute, New York, NY, 10032, United States; College of Physicians and Surgeons of Columbia University, New York, NY, 10032, United States.
authors.forename: D P
authors.initials: DP
authors.lastname: Devanand
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, United States.
authors.forename: Lea T
authors.initials: LT
authors.lastname: Drye
authors.affiliation: Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, Charleston, SC, 29401, United States; Ralph H. Johnson VA Medical Center, SC, 29401, United States.
authors.forename: Jacobo E
authors.initials: JE
authors.lastname: Mintzer
authors.affiliation: Campbell Institute, CAMH, University of Toronto, Toronto, Ontario, M5S 2S1, Canada.
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Pollock
authors.affiliation: University of Rochester School of Medicine and Dentistry, Rochester, NY, 14642, United States.
authors.forename: Anton P
authors.initials: AP
authors.lastname: Porsteinsson
authors.affiliation: University of Southern California Keck School of Medicine, Los Angeles, CA, 90033, United States.
authors.forename: Lon S
authors.initials: LS
authors.lastname: Schneider
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, United States.
authors.forename: David M
authors.initials: DM
authors.lastname: Shade
authors.affiliation: Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, United States; Department of Veterans Affairs, Philadelphia, PA, 19104, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Weintraub
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Bayview Medical Center and Johns Hopkins School of Medicine, Baltimore, MD, 21205, United States.
authors.forename: Constantine G
authors.initials: CG
authors.lastname: Lyketsos
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, 94305-5717, United States.
authors.forename: Art
authors.initials: A
authors.lastname: Noda
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy*; D015283:Citalopram / Q000494:pharmacology*; D004311:Double-Blind Method; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D017063:Outcome Assessment, Health Care; D011595:Psychomotor Agitation / Q000188:drug therapy* / Q000209:etiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
chemical_list: D015283:Citalopram; D006993:Hypnotics and Sedatives; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Agitation; Citalopram; Sedation