Agitation is common, persistent, and associated with adverse
consequences for patients with Alzheimer's disease (AD). Pharmacological
treatment options, including antipsychotics are not satisfactory.
The primary objective was to evaluate the efficacy of citalopram for
agitation in patients with AD. Key secondary objectives examined effects of
citalopram on function, caregiver distress, safety, cognitive safety, and
Design, Setting and Participants
The Citalopram for Agitation in Alzheimer's Disease Study (CitAD) was
a multicenter, randomized, placebo-controlled, double-blind, parallel group
trial that enrolled 186 patients with probable AD and clinically significant
agitation from eight academic centers in the US 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.
Dose began at 10 mg/d with planned titration to 30 mg/d over 3 weeks based
on response and tolerability.
Main Outcomes and Measures
Primary outcome measures were the Neurobehavioral Rating Scale,
agitation subscale (NBRS-A) and the modified Alzheimer Disease Cooperative
Study-Clinical Global Impression of Change (mADCS-CGIC) Other outcomes were
the Cohen-Mansfield Agitation Inventory (CMAI), Neuropsychiatric Inventory
(NPI), activities of daily living (ADLs), caregiver distress, cognitive
safety (MMSE), and adverse events.
Participants on citalopram showed significant improvement compared to
placebo on both primary outcome measures. NBRS-A estimated treatment
difference at week 9 (citalopram minus placebo) was −0.93 [95% CI:
−1.80 to −0.06], p = 0.036. mADCS-CGIC results showed 40% of
citalopram participants having moderate or marked improvement from baseline
compared to 26% on placebo, with estimated treatment effect (odds ratio of
being at or better than a given CGIC category) of 2.13 [95% CI 1.23 to
3.69], p = 0.007. Participants on 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 =
0.026) and QT interval prolongation (18.1 ms [95% CI: 6.1, 30.1], p = 0.004)
were seen in the citalopram group.
Conclusions and Relevance
Among patients with probable Alzheimer's disease and agitation
receiving psychosocial intervention, the addition of citalopram compared
with placebo significantly reduced agitation and caregiver distress, but
cognitive and cardiac adverse effects of citalopram may limit its practical
application at the 30 mg/d dose studied in this trial.