title: Time to Response to Citalopram Treatment for Agitation in Alzheimer Disease.
abstract: OBJECTIVE
  Agitation is a common and significant problem in Alzheimer disease (AD). In the recent Citalopram for Agitation in Alzheimer's Disease (CitAD) study, citalopram was efficacious for the treatment of AD agitation. Here we examined the time course and predictors of response to treatment.
  
  
  METHODS
  Response in CitAD was defined as a modified Alzheimer Disease Cooperative Study Clinical Global Impression of Change (CGIC) score of 1 or 2 or a Neurobehavioral Rating Scale agitation subscale (NBRS-A) score reduction ≥ 50% from baseline. "Stable early response" was defined as meeting the aforementioned criteria at both weeks 3 and 9, "late response" was response at week 9 but not at week 3, and "unstable response" was response at week 3 but not at week 9.
  
  
  RESULTS
  In the primary analyses, citalopram was superior to placebo on both the CGIC and the NBRS-A response measures. Little between-group differences were found in response rates in the first 3 weeks of the study (21% versus 19% on the CGIC). Citalopram patients were more likely than placebo patients to be a late responder (18% versus 8% on CGIC, Fisher's exact p = 0.09; 31% versus 15% on NBRS-A, Fisher's exact p = 0.02). Approximately half of citalopram responders (45%-56%) at end of study achieved response later in the study compared with 30%-44% of placebo responders.
  
  
  CONCLUSIONS
  Treatment with citalopram for agitation in AD needs to be at least 9 weeks in duration to allow sufficient time for full response. Study duration is an important factor to consider in the design of clinical trials for agitation in AD.
authors.affiliation: Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA. Electronic address: daniel.weintraub@uphs.upenn.edu.
authors.forename: Daniel
authors.initials: D
authors.lastname: Weintraub
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
authors.forename: Lea T
authors.initials: LT
authors.lastname: Drye
authors.affiliation: University of Rochester School of Medicine and Dentistry, Rochester, NY.
authors.forename: Anton P
authors.initials: AP
authors.lastname: Porsteinsson
authors.affiliation: Johns Hopkins Bayview and Johns Hopkins School of Medicine, Baltimore, MD.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Rosenberg
authors.affiliation: Campbell Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Pollock
authors.affiliation: Division of Geriatric Psychiatry, New York State Psychiatric Institute and College of Physicians and Surgeons of Columbia University, New York, NY.
authors.forename: Devangere P
authors.initials: DP
authors.lastname: Devanand
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
authors.forename: Constantine
authors.initials: C
authors.lastname: Frangakis
authors.affiliation: Departments of Psychiatry and Neurology, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Zahinoor
authors.initials: Z
authors.lastname: Ismail
authors.affiliation: Johns Hopkins Bayview and Johns Hopkins School of Medicine, Baltimore, MD.
authors.forename: Christopher
authors.initials: C
authors.lastname: Marano
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
authors.forename: Curtis L
authors.initials: CL
authors.lastname: Meinert
authors.affiliation: Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, Charleston, SC.
authors.forename: Jacobo E
authors.initials: JE
authors.lastname: Mintzer
authors.affiliation: Johns Hopkins Bayview and Johns Hopkins School of Medicine, Baltimore, MD.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Munro
authors.affiliation: Division of Geriatric Psychiatry, New York State Psychiatric Institute and College of Physicians and Surgeons of Columbia University, New York, NY.
authors.forename: Gregory
authors.initials: G
authors.lastname: Pelton
authors.affiliation: Johns Hopkins Bayview and Johns Hopkins School of Medicine, Baltimore, MD.
authors.forename: Peter V
authors.initials: PV
authors.lastname: Rabins
authors.affiliation: University of Southern California Keck School of Medicine, Los Angeles, CA.
authors.forename: Lon S
authors.initials: LS
authors.lastname: Schneider
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
authors.forename: David M
authors.initials: DM
authors.lastname: Shade
authors.affiliation: Stanford University School of Medicine and VA Palo Alto Health Care System, Stanford, CA.
authors.forename: Jerome
authors.initials: J
authors.lastname: Yesavage
authors.affiliation: Johns Hopkins Bayview and Johns Hopkins School of Medicine, Baltimore, MD.
authors.forename: Constantine G
authors.initials: CG
authors.lastname: Lyketsos
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy / Q000523:psychology*; D015283:Citalopram / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D011595:Psychomotor Agitation / Q000188:drug therapy*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Agitation; Alzheimer disease; citalopram