title: Estimated dopamine D2 receptor occupancy from plasma concentrations of atypical antipsychotics and subjective experience/drug attitude in schizophrenia: an analysis of the CATIE data.
abstract: OBJECTIVE
  The objective of this analysis was to evaluate both cross-sectional and longitudinal relationships between estimated dopamine D2 receptor occupancy from plasma concentrations of atypical antipsychotics and subjective experience/drug attitude in patients with schizophrenia.
  
  
  METHODS
  The data from the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) were used in this analysis. The cross-sectional data included 371 patients receiving risperidone, olanzapine, or ziprasidone, who had completed the Drug Attitude Inventory (DAI-10) at six months and provided plasma antipsychotic concentrations. Samples were analyzed to examine the relationship between DAI-10 total scores and estimated D2 occupancy using Spearman's rank correlations, followed by multiple regression analysis. In addition, to elucidate the relationship between changes in DAI-10 scores and estimated D2 occupancy, the longitudinal data from 45 patients who experienced an increase in antipsychotic dosage between six and 12months were analyzed. Mean peak and trough D2 occupancy levels were estimated from plasma antipsychotic concentrations using a population pharmacokinetic approach.
  
  
  RESULTS
  A positive association was found between estimated D2 occupancy and DAI-10 total scores in patients receiving ziprasidone in the cross-sectional dataset (rs=0.395, P=0.001). In contrast, a negative association was found in changes in estimated D2 occupancy and DAI-10 scores among patients receiving olanzapine in the longitudinal dataset (rs=-0.534, P=0.010). No significant associations were found in patients receiving risperidone, or in the whole sample regarding both cross-sectional and longitudinal datasets.
  
  
  CONCLUSIONS
  Dopamine D2 receptor occupancy may mediate subjective experience/drug attitude in patients with schizophrenia. The directionality may however differ between antipsychotics, which warrants further investigation.
authors.affiliation: Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; Schizophrenia Division, Complex Mental Illness Program, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, ON, Canada. Electronic address: hirotak@dk9.so-net.ne.jp.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Takefumi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Robert R
authors.initials: RR
authors.lastname: Bies
authors.forename: Gary
authors.initials: G
authors.lastname: Remington
authors.forename: David C
authors.initials: DC
authors.lastname: Mamo
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Pollock
authors.forename: Masaru
authors.initials: M
authors.lastname: Mimura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uchida
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000097:blood* / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003430:Cross-Sectional Studies; D016208:Databases, Factual / Q000706:statistics & numerical data; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011485:Protein Binding / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2
keywords: Antipsychotics; Dopamine; Drug attitude; Schizophrenia; Subjective experience