TY - JOUR
T1 - Changes in QTc interval in the Citalopram for agitation in Alzheimer's Disease (CitAD) randomized trial
AU - Drye, Lea A
AU - Spragg, David
AU - Devanand, D. P.
AU - Frangakis, Constantine
AU - Marano, Christopher Mark
AU - Meinert, Curtis L.
AU - Mintzer, Jacobo E.
AU - Munro, Cynthia A.
AU - Pelton, Gregory
AU - Pollock, Bruce G.
AU - Porsteinsson, Anton P.
AU - Rabins, Peter V.
AU - Rosenberg, Paul B.
AU - Schneider, Lon S.
AU - Shade, David M.
AU - Weintraub, Daniel
AU - Yesavage, Jerome
AU - Lyketsos, Constantine G.
N1 - 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 .
PY - 2014/6/10
Y1 - 2014/6/10
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0098426
DO - 10.1371/journal.pone.0098426
M3 - Article
C2 - 24914549
AN - SCOPUS:84902596807
SN - 1932-6203
VL - 9
JO - PLoS One
JF - PLoS One
IS - 6
M1 - e98426
ER -