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Randomized Controlled Trial
. 2016 Mar;29(2):59-64.
doi: 10.1177/0891988715601735. Epub 2015 Aug 23.

Citalopram for the Treatment of Agitation in Alzheimer Dementia: Genetic Influences

Matthew E Peters  1 , Vijay Vaidya  2 , Lea T Drye  2 , Davangere P Devanand  3 , Jacobo E Mintzer  4 , Bruce G Pollock  5 , Anton P Porsteinsson  6 , Paul B Rosenberg  1 , Lon S Schneider  7 , David M Shade  2 , Daniel Weintraub  8 , Jerome Yesavage  9 , Constantine G Lyketsos  10 , Dimitri Avramopoulos  1 ; CitAD Research Group
Affiliations
Randomized Controlled Trial

Citalopram for the Treatment of Agitation in Alzheimer Dementia: Genetic Influences

Matthew E Peters et al. J Geriatr Psychiatry Neurol. 2016 Mar.

Abstract

Objective: To assess potential genetic influences on citalopram treatment efficacy for agitation in individuals with Alzheimer dementia (AD). Six functional genetic variants were studied in the following genes: serotonin receptor 2A (HTR2A-T102C), serotonin receptor 2C (HTR2C-Cys23Ser), serotonin transporter (5HTT-LPR), brain-derived neurotropic factor (BDNF-Val66Met), apolipoprotein E (ε2, ε3, ε4 variants), and cytochrome P450 (CYP2C19). Treatment response by genotype was measured by (1) the agitation domain of the Neurobehavioral Rating Scale, (2) the modified Alzheimer Disease Cooperative Study-Clinical Global Impression of Change scale (mADCS-CGIC), (3) the agitation domain of the Neuropsychiatric Inventory (NPI), and (4) the Cohen-Mansfield Agitation Inventory.

Method: We utilized data from the Citalopram for Agitation in Alzheimer's Disease (CitAD) database. CitAD was a 9-week randomized, double-blind, placebo-controlled multicenter clinical trial showing significant improvement in agitation and caregiver distress in patients treated with citalopram. Proportional odds logistic regression and mixed effects models were used to examine the above-mentioned outcome measures.

Results: Significant interactions were noted on the NPI agitation domain for HTR2A (likelihood ratio [LR] = 6.19, df = 2, P = .04) and the mADCS-CGIC for HTR2C (LR = 4.33, df = 2, P = .02) over 9 weeks.

Discussion: Treatment outcomes in CitAD showed modest, although statistically significant, influence of genetic variation at HTR2A and HTR2C loci. Future studies should continue to examine the interaction of known genetic variants with antidepressant treatment in patients with AD having agitation.

Keywords: Alzheimer disease; agitation; antidepressant; citalopram; dementia; genetics; randomized trial.

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Conflict of interest statement

Declaration of Conflicting Interests The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article

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