Heterogeneity of Treatment Response to Citalopram for Patients With Alzheimer's Disease With Aggression or Agitation: The CitAD Randomized Clinical Trial. Am J Psychiatry 2016 May 01;173(5):465-72
Date
01/16/2016Pubmed ID
26771737Pubmed Central ID
PMC6419726DOI
10.1176/appi.ajp.2015.15050648Scopus ID
2-s2.0-84965110423 (requires institutional sign-in at Scopus site) 47 CitationsAbstract
OBJECTIVE: Pharmacological treatments for agitation and aggression in patients with Alzheimer's disease have shown limited efficacy. The authors assessed the heterogeneity of response to citalopram in the Citalopram for Agitation in Alzheimer Disease (CitAD) study to identify individuals who may be helped or harmed.
METHOD: In this double-blind parallel-group multicenter trial of 186 patients with Alzheimer's disease and clinically significant agitation, participants were randomly assigned to receive citalopram or placebo for 9 weeks, with the dosage titrated to 30 mg/day over the first 3 weeks. Five planned potential predictors of treatment outcome were assessed, along with six additional predictors. The authors then used a two-stage multivariate method to select the most likely predictors; grouped participants into 10 subgroups by their index scores; and estimated the citalopram treatment effect for each.
RESULTS: Five covariates were likely predictors, and treatment effect was heterogeneous across the subgroups. Patients for whom citalopram was more effective were more likely to be outpatients, have the least cognitive impairment, have moderate agitation, and be within the middle age range (76-82 years). Patients for whom placebo was more effective were more likely to be in long-term care, have more severe cognitive impairment, have more severe agitation, and be treated with lorazepam.
CONCLUSIONS: Considering several covariates together allowed the identification of responders. Those with moderate agitation and with lower levels of cognitive impairment were more likely to benefit from citalopram, and those with more severe agitation and greater cognitive impairment were at greater risk for adverse responses. Considering the dosages used and the association of citalopram with cardiac QT prolongation, use of this agent to treat agitation may be limited to a subgroup of people with dementia.
Author List
Schneider LS, Frangakis C, Drye LT, Devanand DP, Marano CM, Mintzer J, Mulsant BH, Munro CA, Newell JA, Pawluczyk S, Pelton G, Pollock BG, Porsteinsson AP, Rabins PV, Rein L, Rosenberg PB, Shade D, Weintraub D, Yesavage J, Lyketsos CG, CitAD Research GroupAuthor
Lisa E. Rein Biostatistician III in the Institute for Health and Equity department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AgedAged, 80 and over
Aggression
Alzheimer Disease
Antidepressive Agents, Second-Generation
Citalopram
Double-Blind Method
Female
Humans
Male
Middle Aged
Psychomotor Agitation
Risk Factors
Treatment Outcome
