Dataset Information

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.

SUBMITTER: Drye LT

PROVIDER: S-EPMC4051660 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Changes in QTc interval in the citalopram for agitation in Alzheimer's disease (CitAD) randomized trial.

Drye Lea T LT Spragg David D Devanand D P DP Frangakis Constantine C Marano Christopher C Meinert Curtis L CL Mintzer Jacobo E JE Munro Cynthia A CA Pelton Gregory G Pollock Bruce G BG Porsteinsson Anton P AP Rabins Peter V PV Rosenberg Paul B PB Schneider Lon S LS Shade David M DM Weintraub Daniel D Yesavage Jerome J Lyketsos Constantine G CG

PloS one 20140610 6

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 24914549

Similar Datasets

Project description:Agitation is common, persistent, and associated with adverse consequences for patients with Alzheimer disease. Pharmacological treatment options, including antipsychotics are not satisfactory.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.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.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.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.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.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.clinicaltrials.gov Identifier: NCT00898807.

Dataset Information

Changes in QTc interval in the citalopram for agitation in Alzheimer's disease (CitAD) randomized trial.

Background

Methods

Results

Conclusion

Trial registration

Publications

Changes in QTc interval in the citalopram for agitation in Alzheimer's disease (CitAD) randomized trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure