citalopram improves Alzheimer's agitation

JAMA this week reported on the use of citalopram for agitation in people with Alzheimer's disease (see alzheimer agitation citalopram jama 2014 in dropbox, or doi:10.1001/jama.2014.93). details:

    --double-blind study of 186 pts with probable alzheimer's and agitation (mean age 78, 46% women, 65% white, 70% on cholinesterase inhibitor and 42% on memantine) at 8 US and Canadian academic sites, all with 9 week psychosocial intervention, half with citalopram (began at 10mg, titrated up to 30mg over 3 weeks, and with 78% achieving the 30mg target). psychosocial intervention consisted of giving educational material, 24-hr availability for crisis management, and 20-30 minute counseling session at each visit, focusing on reviewing/adjusting supportive care plan, providing emotional support, counseling regarding specific caregiver skills, and assistance with problem solving on specific caregiver/patient issues.  At 9 weeks:

    --18-point Neurobehavioral Rating Scale agitation subscale (NBRS-A) with 1 point improvement (felt by editorialist to be clinically significant) with citalopram.
    --modified Alzheimer Disease Cooperative Study- Clinical Global Impression of Change (mADCS-CGIC) found 40% on citalopram to have moderate or marked improvement, vs 26% placebo. (OR 2.13)
    --those on citalopram also had improved Cohen-Mansfield Agitation Inventory, Neuropsychiatric Inventory, and caregiver distress scores (but, no improvement in Neuropsychiatric Inventory scale, ability to complete ADLs, or in less use of rescue lorazepam,  AND there was worsening of cognition by 1 point on Mini Mental Status Exam (though unclear clinical relevance of this small a change; typically a 1.4 point change is considered significant) and increase in QTc by 18.1msec.

so, a few points of interest.

--neuropsych sx are really common in Alzheimer's. antipsychotics have been used lots in the past, with unclear efficacy in the studies, and increased mortality (though they certainly seemed to work in some of my patients...)
--given the FDA warning about citalopram dosing and increased QTc, lower doses and closer EKG monitoring seems reasonable. i have sent out past email/blog confirming that there is a pretty dramatic increase in QTc with citalopram, but it is important to note that the actual clinical effect of this prolongation is NOT clear: the FDA looked at a large VA database and found that the risk of ventricular arrhythmias and mortality were LOWER in depressed patients on greater than 40mg citalopram/day, similar results to those found in patients on sertraline (i have largely shifted to sertraline as my "go-to" antidepressant overall, away from citalopram because of the QTc issue, but still use citalopram if sertraline not tolerated). anecdotally, a geriatric psychiatrist i know has been using sertraline for agitation in people with Alzheimers, with good effect. citalopram in this study was well-tolerated.
--overall, very impressive but short-term study. i would certainly prioritize nonpharmacologic management, but if insufficient, finding a 40% moderate to marked improvement with decreased agitation is very impressive.