Heterogeneity of Treatment Response to Citalopram for Patients With Alzheimer's Disease With Aggression or Agitation: The CitAD Randomized Clinical Trial.

Abstract

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.

• Authors: Lon S Schneider, Constantine Frangakis, Lea T Drye, D P Devanand, Christopher M Marano, Jacob Mintzer, Benoit H Mulsant, Cynthia A Munro, Jeffery A Newell, Sonia Pawluczyk, Gregory Pelton, Bruce G Pollock, Anton P Porsteinsson, Peter V Rabins, Lisa Rein, Paul B Rosenberg, David Shade, Daniel Weintraub, Jerome Yesavage, Constantine G Lyketsos, CitAD Research Group
• Journal: The American journal of psychiatry (Am J Psychiatry) Vol. 173 Issue 5 Pg. 465-72 (May 01 2016) ISSN: 1535-7228 [Electronic] United States
• PMID: 26771737 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Antidepressive Agents, Second-Generation
• Citalopram

Topics

• Aged
• Aged, 80 and over
• Aggression (drug effects)
• Alzheimer Disease (complications, drug therapy, psychology)
• Antidepressive Agents, Second-Generation (therapeutic use)
• Citalopram (therapeutic use)
• Double-Blind Method
• Female
• Humans
• Male
• Middle Aged
• Psychomotor Agitation (complications, drug therapy)
• Risk Factors
• Treatment Outcome