@article{fb0411cb282847c297e53b1c04426140,
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. Conclusion: Citalopram at 30 mg/day was associated with improvement in agitation in patients with AD but was also associated with QT prolongation. Trial Registration: ClinicalTrials.gov NCT00898807.",
author = "Drye, {Lea T.} and David Spragg and Devanand, {D. P.} and Constantine Frangakis and Christopher Marano and Meinert, {Curtis L.} and Mintzer, {Jacobo E.} and Munro, {Cynthia A.} and Gregory Pelton and Pollock, {Bruce G.} and Porsteinsson, {Anton P.} and Rabins, {Peter V.} and Rosenberg, {Paul B.} and Schneider, {Lon S.} and Shade, {David M.} and Daniel Weintraub and Jerome Yesavage and Lyketsos, {Constantine G.}",
note = "Funding Information: CitAD was an investigator-initiated clinical trial funded by the National Institute on Aging (NIA) and National Institute of Mental Health (NIMH) than enrolled participants from August 2009 to January 2013. CitAD is registered at clinicaltrials.gov: NCT00898807. The study had eight recruiting clinical centers (seven in the U.S. and one in Canada) and two resource centers (the chair's office and the coordinating center). Study participants were recruited from memory clinics, geriatric psychiatry clinics, Veterans Administration geriatric clinics, nursing homes, community outreach, and Alzheimer Research Centers. CitAD participants had probable Alzheimer's disease as defined by NINCDS-ADRDA criteria, Mini-Mental State Examination (MMSE) scores of 5–28 inclusive, and clinically significant agitation. The detailed list of eligibility criteria for CitAD has been published previously . The protocol for CitAD and supporting CONSORT checklist are available as supporting information; see and . Funding Information: The authors have read the journal's policy and have the following conflicts. Dr. Porsteinsson reports receiving research funding from Avanir, Baxter, BMS, Elan, EnVivo, Genentech/Roche, Janssen Alzheimer Initiative, Merck, Pfizer, Toyama, Medivation, National Institutes of Health (NIH), and Department of Defense; is a paid consultant for Elan, Janssen Alzheimer Initiative, and Pfizer; is a board member on Data Safety and Monitoring Boards for Quintiles, Functional Neuromodulation, and New York State Psychiatric Institute; participated on a Speaker's Bureau for Forest and developed educational presentations for CME, inc. Dr. Pollock reports being a board member on Data Safety and Monitoring Boards for Lundbeck Canada; is a paid consultant for Wyeth; has received travel and accommodation expenses from Lundbeck International Neuroscience Foundation. Dr. Devanand reports receiving grant funding from the NIH and Eli Lilly. Dr. Ismail reports being paid for lectures by Calgary Foothills Primary Care Network, Calgary West Central Primary Care Network, Canadian Conference on Dementia, Alberta College of Family Physicians, and University of British Columbia and is a paid consultant for Astra Zeneca, Janssen, Lundbeck, Otsuka, Pfizer, and Sunovion. Dr. Meinert reports receiving grant funding from the NIH. Dr. Mintzer reports receiving research funding from Accera, Avanir, Baxter, Elan, Eli Lilly, F. Hoffmann-La Roche, Genentech, Janssen Alzheimer Initiative, Merck, Novartis, Pfizer, Takeda Global Research & Development Center, Wyeth, and NIH; he is employed by Roper St. Francis Healthcare, Medical University of South Carolina, Ralph H. Johnson VA Medical Center, and NeuroQuest and is founder of BioPharma Connex. Dr. Munro reports receiving grant funding from the NIH; being paid for expert testimony from various law firms, Office of Federal Public Defender, and US Attorney's Office; and being paid for lectures for Episcopal Ministries. Dr. Rabins reports being paid for legal testimony from Janssen. Dr. Rosenberg reports receiving research funding from Elan, Eli Lilly, Merck, and Functional Neuromodulation, Inc.; is a paid consultant for Janssen and Pfizer; has developed educational presentations for Eli Lilly. Dr. Schneider reports receiving grant funding from the NIH; is a paid consultant for Forest Laboratories, Eli Lilly, Astra Zeneca, Johnson and Johnson, Bristol Myers Squibb and Otsuka, and Abbott and Abbvie. Dr. Lyketsos reports receiving grant funding from the NIH; is a paid consultant for Avanir, BMS, Elan, Eli Lilly, Genentech, GSK, Janssen, Novartis, NFL, and Pfizer; reports being a board member on Data Safety and Monitoring Boards for Eli Lilly and Janssen; and receiving royalties from Oxford University Press. Drs. Drye, Spragg, Frangakis, Marano, Pelton, Weintraub, Yesavage and Mr. Shade report no conflicts of interest. ",
year = "2014",
month = jun,
day = "10",
doi = "10.1371/journal.pone.0098426",
language = "English (US)",
volume = "9",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "6",
}