TY - JOUR
T1 - Citalopram for the Treatment of Agitation in Alzheimer Dementia
AU - Peters, Matthew E.
AU - Vaidya, Vijay
AU - Drye, Lea T.
AU - Devanand, Davangere P.
AU - Mintzer, Jacobo E.
AU - Pollock, Bruce G.
AU - Porsteinsson, Anton P.
AU - Rosenberg, Paul B.
AU - Schneider, Lon S.
AU - Shade, David M.
AU - Weintraub, Daniel
AU - Yesavage, Jerome
AU - Lyketsos, Constantine G.
AU - Avramopoulos, Dimitri
N1 - Publisher Copyright:
© 2015 SAGE Publications.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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 (∈2, ∈3, ∈4 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.
AB - 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 (∈2, ∈3, ∈4 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.
KW - Alzheimer disease
KW - agitation
KW - antidepressant
KW - citalopram
KW - dementia
KW - genetics
KW - randomized trial
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U2 - 10.1177/0891988715601735
DO - 10.1177/0891988715601735
M3 - Article
C2 - 26303700
AN - SCOPUS:84957682406
SN - 0891-9887
VL - 29
SP - 59
EP - 64
JO - Journal of Geriatric Psychiatry and Neurology
JF - Journal of Geriatric Psychiatry and Neurology
IS - 2
ER -