title: Citalopram for the Treatment of Agitation in Alzheimer Dementia: Genetic Influences.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors: Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Matthew E
authors: ME
authors: Peters
authors: Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors: Vijay
authors: V
authors: Vaidya
authors: Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors: Lea T
authors: LT
authors: Drye
authors: Columbia University Medical Center, New York, NY, USA.
authors: Davangere P
authors: DP
authors: Devanand
authors: Medical University of South Carolina, Charleston, SC, USA.
authors: Jacobo E
authors: JE
authors: Mintzer
authors: Centre for Addiction and Mental Health, Campbell Family Institute, Toronto, Canada University of Toronto, Toronto, Canada.
authors: Bruce G
authors: BG
authors: Pollock
authors: University of Rochester School of Medicine, Rochester, NY, USA.
authors: Anton P
authors: AP
authors: Porsteinsson
authors: Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Paul B
authors: PB
authors: Rosenberg
authors: Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
authors: Lon S
authors: LS
authors: Schneider
authors: Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors: David M
authors: DM
authors: Shade
authors: University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors: Daniel
authors: D
authors: Weintraub
authors: Stanford University School of Medicine, Stanford, CA, USA.
authors: Jerome
authors: J
authors: Yesavage
authors: Johns Hopkins University School of Medicine, Baltimore, MD, USA kostas@jhmi.edu.
authors: Constantine G
authors: CG
authors: Lyketsos
authors: Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Dimitri
authors: D
authors: Avramopoulos
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics*; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001057:Apolipoproteins E / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D017028:Caregivers / Q000523:psychology; D015283:Citalopram / Q000627:therapeutic use*; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics; D016208:Databases, Factual; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D011595:Psychomotor Agitation / Q000150:complications / Q000188:drug therapy* / Q000235:genetics*; D011985:Receptors, Serotonin / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D001057:Apolipoproteins E; D019208:Brain-Derived Neurotrophic Factor; D015283:Citalopram; D065731:Cytochrome P-450 CYP2C19; D011985:Receptors, Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C579455:BDNF protein, human; C045793:CYP2C19 protein, human
keywords: Alzheimer disease; agitation; antidepressant; citalopram; dementia; genetics; randomized trial