Citalopram for the Treatment of Agitation in Alzheimer Dementia: Genetic Influences. (March 2016)

• Record Type: Journal Article
• Authors: Peters, Matthew E.; Vaidya, Vijay; Drye, Lea T.; Devanand, Davangere P.; Mintzer, Jacobo E.; Pollock, Bruce G.; Porsteinsson, Anton P.; Rosenberg, Paul B.; Schneider, Lon S.; Shade, David M.; Weintraub, Daniel; Yesavage, Jerome; Lyketsos, Constantine G.; Avramopoulos, Dimitri
• Is Part Of: Journal of geriatric psychiatry and neurology. Volume 29:Number 2(2016)
• Page Start: 59
• Page End: 64
• Publication Date: 2016-03
• Subjects: Alzheimer disease -- citalopram -- agitation -- randomized trial -- dementia -- antidepressant -- genetics; Geriatric neurology -- Periodicals; Geriatric neuropsychiatry -- Periodicals; Geriatric psychiatry -- Periodicals; Nervous system -- Diseases -- Periodicals; 618.97689
• DOI: 10.1177/0891988715601735
• Languages: English
• ISSNs: 0891-9887

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.