title: Effect of citalopram on agitation in Alzheimer disease: the CitAD randomized clinical trial.
abstract: OBJECTIVE
  Agitation is common, persistent, and associated with adverse consequences for patients with Alzheimer disease. Pharmacological treatment options, including antipsychotics are not satisfactory.
  
  
  OBJECTIVE
  The primary objective was to evaluate the efficacy of citalopram for agitation in patients with Alzheimer disease. Key secondary objectives examined effects of citalopram on function, caregiver distress, safety, cognitive safety, and tolerability.
  
  
  METHODS
  The Citalopram for Agitation in Alzheimer Disease Study (CitAD) was a randomized, placebo-controlled, double-blind, parallel group trial that enrolled 186 patients with probable Alzheimer disease and clinically significant agitation from 8 academic centers in the United States and Canada from August 2009 to January 2013.
  
  
  METHODS
  Participants (n = 186) were randomized to receive a psychosocial intervention plus either citalopram (n = 94) or placebo (n = 92) for 9 weeks. Dosage began at 10 mg per day with planned titration to 30 mg per day over 3 weeks based on response and tolerability.
  
  
  METHODS
  Primary outcome measures were based on scores from the 18-point Neurobehavioral Rating Scale agitation subscale (NBRS-A) and the modified Alzheimer Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC). Other outcomes were based on scores from the Cohen-Mansfield Agitation Inventory (CMAI) and the Neuropsychiatric Inventory (NPI), ability to complete activities of daily living (ADLs), caregiver distress, cognitive safety (based on scores from the 30-point Mini Mental State Examination [MMSE]), and adverse events.
  
  
  RESULTS
  Participants who received citalopram showed significant improvement compared with those who received placebo on both primary outcome measures. The NBRS-A estimated treatment difference at week 9 (citalopram minus placebo) was -0.93 (95% CI, -1.80 to -0.06), P = .04. Results from the mADCS-CGIC showed 40% of citalopram participants having moderate or marked improvement from baseline compared with 26% of placebo recipients, with estimated treatment effect (odds ratio [OR] of being at or better than a given CGIC category) of 2.13 (95% CI, 1.23-3.69), P = .01. Participants who received citalopram showed significant improvement on the CMAI, total NPI, and caregiver distress scores but not on the NPI agitation subscale, ADLs, or in less use of rescue lorazepam. Worsening of cognition (-1.05 points; 95% CI, -1.97 to -0.13; P = .03) and QT interval prolongation (18.1 ms; 95% CI, 6.1-30.1; P = .01) were seen in the citalopram group.
  
  
  CONCLUSIONS
  Among patients with probable Alzheimer disease and agitation who were receiving psychosocial intervention, the addition of citalopram compared with placebo significantly reduced agitation and caregiver distress; however, cognitive and cardiac adverse effects of citalopram may limit its practical application at the dosage of 30 mg per day.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00898807.
authors.affiliation: University of Rochester School of Medicine and Dentistry, Rochester, New York.
authors.forename: Anton P
authors.initials: AP
authors.lastname: Porsteinsson
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Lea T
authors.initials: LT
authors.lastname: Drye
authors.affiliation: Campbell Institute, CAMH, 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, New York5College of Physicians and Surgeons of Columbia University, New York, New York.
authors.forename: D P
authors.initials: DP
authors.lastname: Devanand
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
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, Maryland.
authors.forename: Christopher
authors.initials: C
authors.lastname: Marano
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Curtis L
authors.initials: CL
authors.lastname: Meinert
authors.affiliation: Clinical Biotechnology Research Institute, Roper St Francis Healthcare, Charleston, South Carolina.
authors.forename: Jacobo E
authors.initials: JE
authors.lastname: Mintzer
authors.affiliation: Johns Hopkins Bayview and Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Munro
authors.affiliation: Division of Geriatric Psychiatry, New York State Psychiatric Institute, New York.
authors.forename: Gregory
authors.initials: G
authors.lastname: Pelton
authors.affiliation: Johns Hopkins Bayview and Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Peter V
authors.initials: PV
authors.lastname: Rabins
authors.affiliation: Johns Hopkins Bayview and Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Rosenberg
authors.affiliation: University of Southern California Keck School of Medicine, Los Angeles.
authors.forename: Lon S
authors.initials: LS
authors.lastname: Schneider
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: David M
authors.initials: DM
authors.lastname: Shade
authors.affiliation: Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
authors.forename: Daniel
authors.initials: D
authors.lastname: Weintraub
authors.affiliation: Stanford University School of Medicine, Stanford, California12VA Palo Alto Health Care System, Stanford, California.
authors.forename: Jerome
authors.initials: J
authors.lastname: Yesavage
authors.affiliation: Johns Hopkins Bayview and Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Constantine G
authors.initials: CG
authors.lastname: Lyketsos
mesh_terms: D000203:Activities of Daily Living; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications* / Q000451:nursing / Q000503:physiopathology; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D017028:Caregivers / Q000523:psychology; D015283:Citalopram / Q000009:adverse effects / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D011595:Psychomotor Agitation / Q000188:drug therapy* / Q000209:etiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013315:Stress, Psychological; D016896:Treatment Outcome
chemical_list: D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors