title: Changes in QTc interval in the citalopram for agitation in Alzheimer's disease (CitAD) randomized trial.
abstract: BACKGROUND
  A Food and Drug Administration (FDA) safety communication in August 2011 warned that citalopram was associated with a dose dependent risk of QT prolongation and recommended dose restriction in patients over the age of 60 but did not provide data for this age group.
  
  
  METHODS
  CitAD was a randomized, double-masked, placebo-controlled, multicenter clinical trial for agitation in Alzheimer's disease (AD). Participants were assigned to citalopram (target dose of 30 mg/day) or placebo in a 1 ∶ 1 ratio. 186 people, 181 of whom were over the age of 60, having probable AD with clinically significant agitation were recruited from September 2009 to January 2013. After the FDA safety communication about citalopram, ECG was added to the required study procedures before enrollment and repeated at week 3 to monitor change in QTc interval. Forty-eight participants were enrolled after enhanced monitoring began.
  
  
  RESULTS
  Citalopram treatment was associated with a larger increase in QTc interval than placebo (difference in week 3 QTc adjusting for baseline QTc: 18.1 ms [95% CI: 6.1, 30.1]; p = 0.004). More participants in the citalopram group had an increase ≥ 30 ms from baseline to week 3 (7 in citalopram versus 1 in placebo; Fisher's exact p = 0.046), but only slightly more in the citalopram group met a gender-specific threshold for prolonged QTc (450 ms for males; 470 ms for females) at any point during follow-up (3 in citalopram versus 1 in placebo, Fisher's exact p = 0.611). One of the citalopram participants who developed prolonged QTc also displayed ventricular bigeminy. No participants in either group had a cardiovascular-related death.
  
  
  CONCLUSIONS
  Citalopram at 30 mg/day was associated with improvement in agitation in patients with AD but was also associated with QT prolongation.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00898807.
authors.affiliation: Department of Epidemiology and Center for Clinical Trials, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Lea T
authors.initials: LT
authors.lastname: Drye
authors.affiliation: Electrophysiology Laboratory, Johns Hopkins Hospital and Johns Hopkins Bayview Medical Center, Baltimore, Maryland, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Spragg
authors.affiliation: Division of Geriatric Psychiatry, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America.
authors.forename: D P
authors.initials: DP
authors.lastname: Devanand
authors.affiliation: Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Constantine
authors.initials: C
authors.lastname: Frangakis
authors.affiliation: Division of Geriatric Psychiatry and Neuropsychiatry, Johns Hopkins University School of Medicine, Johns Hopkins Bayview Medical Center, Baltimore, Maryland, United States of America.
authors.forename: Christopher
authors.initials: C
authors.lastname: Marano
authors.affiliation: Departments of Epidemiology and Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Curtis L
authors.initials: CL
authors.lastname: Meinert
authors.affiliation: Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, Department of Health Studies, Medical University of South Carolina, Ralph H. Johnson VA Medical Center, Charleston, South Carolina, United States of America.
authors.forename: Jacobo E
authors.initials: JE
authors.lastname: Mintzer
authors.affiliation: Departments of Psychiatry and Behavioral Sciences and Neurology, Johns Hopkins Bayview and Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Munro
authors.affiliation: Division of Geriatric Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons of Columbia University, New York, New York, United States of America.
authors.forename: Gregory
authors.initials: G
authors.lastname: Pelton
authors.affiliation: Campbell Family Mental Health Research Institute, Division of Geriatric Psychiatry and Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Pollock
authors.affiliation: Alzheimer's Disease Care, Research and Education Program (AD-CARE), University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America.
authors.forename: Anton P
authors.initials: AP
authors.lastname: Porsteinsson
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine and Johns Hopkins Hospital, Baltimore, Maryland, United States of America.
authors.forename: Peter V
authors.initials: PV
authors.lastname: Rabins
authors.affiliation: Department of Psychiatry and Behavioral Sciences, John Hopkins University School of Medicine and Johns Hopkins Bayview Medical Center, Baltimore, Maryland, United States of America.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Rosenberg
authors.affiliation: Departments of Psychiatry, Neurology, and Gerontology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Lon S
authors.initials: LS
authors.lastname: Schneider
authors.affiliation: Departments of Medicine (Pulmonary) and Epidemiology and Center for Clinical Trials, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: David M
authors.initials: DM
authors.lastname: Shade
authors.affiliation: Departments of 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, United States of America.
authors.forename: Daniel
authors.initials: D
authors.lastname: Weintraub
authors.affiliation: Aging Clinical Research Center, Mental Illness Research Education and Clinical Center, Veterans Affairs Palo Alto Health Care System, Departments of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California, United States of America.
authors.forename: Jerome
authors.initials: J
authors.lastname: Yesavage
authors.affiliation: Memory and Alzheimer's Treatment Center, Department of Psychiatry and Behavioral Sciences, Johns Hopkins Bayview and Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Constantine G
authors.initials: CG
authors.lastname: Lyketsos
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy*; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D066126:Cardiotoxicity; D015283:Citalopram / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D011595:Psychomotor Agitation / Q000150:complications / Q000188:drug therapy*
chemical_list: D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram