Effect of citalopram on agitation in Alzheimer disease: the CitAD randomized clinical trial.


This randomized controlled trial found that for patients with Alzheimer disease and agitation, addition of citalopram was associated with significantly reduced agitation and caregiver distress. Side effects occurring more frequently with citalopram included increase in QTc interval, worsening MMSE scores, and GI upset.


  • Randomized Controlled Trial.
  • N=186 participants with probable Alzheimer disease and clinically significant agitation receiving psychosocial intervention, randomized to receive 9 weeks of:
    • Citalopram (n=94)
    • Placebo (n=92)
  • Dosing began at 10mg/day and was titrated to 30mg/day over 3 weeks.
  • Setting: 8 academic centers in the U.S. and Canada, from 2009-2013.
  • Participants were 46% female, 65% white, mean age 78 years old, mean duration of dementia 5 years, mean baseline MMSE=15.7, 69% using cholinesterase inhibitors, 42% using memantine.
  • Primary outcomes:
    • Neurobehavioral Rating Scale agitation subscale (NBRS-A)
    • Modified Alzheimer Disease Cooperative Study-Clinical Global Impressions of Change (mADCS-CGIC)
  • Secondary outcomes:
    • Cohen-Mansfield Agitation Inventory (CMAI)
    • Neuropsychiatric Inventory (NPI)
    • Completion of ADLs
    • Cognitive safety (based on MMSE)


  • Citalopram was associated with significant improvement in both primary outcomes, compared with placebo.
  • NBRS-A estimated score at 9 weeks was significantly lower for the citalopram group, compared with placebo (P=0.04):
    • 4.33 for citalopram
    • 5.26 for placebo
  • Moderate or marked improvement from baseline occurred at a significantly higher rate in the citalopram group, based on mADCS-CGIC (P=0.01):
    • 40% of citalopram group
    • 26% of placebo group
  • Use of rescue lorazepam and ability to perform ADLs did not differ significantly between the two groups.
  • NPI-total score at 9 weeks was significantly lower in the citalopram group compared with placebo (P=0.01), as was NPI caregiver distress subscore (P=0.02). The NPI-agitation subscale favored citalopram but did not reach statistical significance (P=0.12).
  • MMSE scores showed greater cognitive worsening at 9 weeks with citalopram, compared with placebo (-1.05 points; P=0.03).
  • QTc interval increased significantly more in the citalopram group (18.1ms; P=0.05).
  • Rates of hyponatremia did not differ significantly between the groups.
  • Side effects occurring significantly more commonly with:
    • Citalopram: anorexia, diarrhea, fever
    • Placebo: weight loss, insomnia


Porsteinsson AP, Drye LT, Pollock BG, et al. Effect of citalopram on agitation in Alzheimer disease: the CitAD randomized clinical trial. JAMA. 2014;311(7):682-691. doi:10.1001/jama.2014.93.

View on PubMed