TY - JOUR
T1 - Heterogeneity of treatment response to citalopram for patients with Alzheimer's disease with aggression or agitation
T2 - The citad randomized clinical trial
AU - For the CitAD Research Group
AU - Schneider, Lon S.
AU - Frangakis, Constantine
AU - Drye, Lea T.
AU - Devanand, D. P.
AU - Marano, Christopher M.
AU - Mintzer, Jacob
AU - Mulsant, Benoit H.
AU - Munro, Cynthia A.
AU - Newell, Jeffery A.
AU - Pawluczyk, Sonia
AU - Pelton, Gregory
AU - Pollock, Bruce G.
AU - Porsteinsson, Anton P.
AU - Rabins, Peter V.
AU - Rein, Lisa
AU - Rosenberg, Paul B.
AU - Shade, David
AU - Weintraub, Daniel
AU - Yesavage, Jerome
AU - Lyketsos, Constantine G.
N1 - Funding Information:
Supported by National Institute on Aging and NIMH grant R01 AG031348 and in part by NIH grant P50 AG05142.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - 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 thisdouble-blindparallel-groupmulticenter trialof 186 patients with Alzheimer's disease and clinically significant agitation, participants were randomly assigned to receive citalopramor placebo for 9 weeks, with the dosage titrated to 30 mg/day over the first 3 weeks. Five planned potential predictors of treatmentoutcomewere 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 forwhomplacebo 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.
AB - 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 thisdouble-blindparallel-groupmulticenter trialof 186 patients with Alzheimer's disease and clinically significant agitation, participants were randomly assigned to receive citalopramor placebo for 9 weeks, with the dosage titrated to 30 mg/day over the first 3 weeks. Five planned potential predictors of treatmentoutcomewere 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 forwhomplacebo 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.
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U2 - 10.1176/appi.ajp.2015.15050648
DO - 10.1176/appi.ajp.2015.15050648
M3 - Article
C2 - 26771737
AN - SCOPUS:84965110423
SN - 0002-953X
VL - 173
SP - 465
EP - 472
JO - American Journal of Psychiatry
JF - American Journal of Psychiatry
IS - 5
ER -