title: Lack of Early Improvement with Antipsychotics is a Marker for Subsequent Nonresponse in Behavioral and Psychological Symptoms of Dementia: Analysis of CATIE-AD Data.
abstract: OBJECTIVE
  Prediction of response or nonresponse to antipsychotics is especially important in patients with behavioral and psychological symptoms of dementia (BPSD) in whom antipsychotic exposure increases risks of death. This study examined whether the presence or absence of early improvement of BPSD with antipsychotics is associated with subsequent response or nonresponse.
  
  
  METHODS
  In a post-hoc analysis of the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) study (2001-2004) (clinicaltrials.gov; NCT00015548) in 45 U.S. sites, 245 subjects (olanzapine, N = 90; quetiapine, N = 81; risperidone, N = 74) with a DSM-IV diagnosis of dementia of the Alzheimer type who presented with a score of 1 or more in the Brief Psychiatric Rating Scale (BPRS) at baseline (phase I of CATIE-AD) were randomly assigned to treatment with olanzapine, quetiapine, risperidone, or placebo in a double-blind manner. Associations were examined between response at week 8 and demographic and clinical characteristics, including BPRS total score reduction at week 2, using logistic regression analyses. Prediction performance of binary classification (presence or absence) of improvement or no improvement at week 2 for response at week 8 was examined.
  
  
  RESULTS
  BPRS total score reduction at week 2 (mean percentage score reduction: 12.6%) was significantly associated with response at week 8 (odds ratio: 1.18; 95% CI: 1.11-1.26). The 5% score reduction cut-off at week 2 showed the highest accuracy (0.71), with sensitivity, specificity, and positive and negative predictivevalues of 0.76, 0.65, 0.69, and 0.72, respectively.
  
  
  CONCLUSIONS
  Lack of even a very small early improvement with antipsychotic treatment may be a marker of subsequent nonresponse in BPSD.
authors.affiliation: Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Center for Clinical Research, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Rachel
authors.initials: R
authors.lastname: Roberts
authors.affiliation: Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; Department of Psychiatry, Inokashira Hospital, Tokyo, Japan.
authors.forename: Takefumi
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Psychiatry, University of California, San Diego, CA.
authors.forename: Barry
authors.initials: B
authors.lastname: Lebowitz
authors.affiliation: Division of Psychiatry, University College London, London, United Kingdom; Department of Old Age Psychiatry, Institute of Psychiatry, King's College London, London, United Kingdom.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Reeves
authors.affiliation: Division of Psychiatry, University College London, London, United Kingdom; Department of Old Age Psychiatry, Institute of Psychiatry, King's College London, London, United Kingdom.
authors.forename: Robert
authors.initials: R
authors.lastname: Howard
authors.affiliation: Center for Clinical Research, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Abe
authors.affiliation: Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Mimura
authors.affiliation: Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. Electronic address: hiroyuki.uchida.hu@gmail.com.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uchida
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy*; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001526:Behavioral Symptoms / Q000150:complications / Q000188:drug therapy*; D001569:Benzodiazepines / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D000069348:Quetiapine Fumarate / Q000627:therapeutic use*; D018967:Risperidone / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D018967:Risperidone; D000077152:Olanzapine
keywords: Antipsychotics; CATIE-AD; behavioral and psychological symptoms with dementia (BPSD); dementia; prediction; response