title: Challenging the need for sustained blockade of dopamine D₂ receptor estimated from antipsychotic plasma levels in the maintenance treatment of schizophrenia: A single-blind, randomized, controlled study.
abstract: OBJECTIVE
  Blockade of dopamine D₂ receptors with antipsychotics above 65% is associated with optimal chance of clinical response although recent data suggest a lower threshold for the maintenance treatment of schizophrenia. The objective of this study was to prospectively examine whether such continuous high blockade would be necessary for maintenance treatment.
  
  
  METHODS
  In this single-blind, 52-week, randomized controlled trial, clinically stable patients with schizophrenia receiving risperidone or olanzapine were randomly assigned to the continuous D₂ blockade (i.e. an estimated trough D2 blockade of >65%) or non-continuous blockade group (i.e. an estimated peak level of >65% with an estimated trough level of <65%). Oral doses corresponding to the assigned blockade levels were estimated from random plasma drug concentrations, using the models we developed; antipsychotic doses were then adjusted accordingly. Psychopathology and side effects were assessed at baseline and one year with the Positive and Negative Syndrome Scale (PANSS), Simpson-Angus Scale (SAS), and Abnormal Involuntary Movement Scale (AIMS).
  
  
  RESULTS
  Sixty-eight subjects (34 in each group) were enrolled. Twenty-six (76.5%) and thirty-one (91.2%) subjects completed the study in the continuous and non-continuous blockade groups, respectively, without any significant group difference. No significant differences were found on any of the assessment scales between the two groups. The degree of dosage change was small in both groups.
  
  
  CONCLUSIONS
  These results offer support that the threshold for D₂ receptor blockade in the maintenance treatment can be lower than 65%. However, these preliminary findings have to be confirmed through double-blind, larger scale trials with longer follow-up periods.
authors: Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
authors: Takashi
authors: T
authors: Tsuboi
authors: Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; Department of Psychiatry, Inokashira Hospital, Tokyo, Japan.
authors: Takefumi
authors: T
authors: Suzuki
authors: Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana Clinical and Translational Sciences Institute, Indianapolis, IN, USA; Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors: Robert R
authors: RR
authors: Bies
authors: Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors: Gary
authors: G
authors: Remington
authors: Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors: Bruce G
authors: BG
authors: Pollock
authors: Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
authors: Masaru
authors: M
authors: Mimura
authors: Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, ON, Canada. Electronic address: hiroyuki.uchida.hu@gmail.com.
authors: Hiroyuki
authors: H
authors: Uchida
mesh_terms: D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000097:blood* / Q000627:therapeutic use*; D065127:Dopamine D2 Receptor Antagonists / Q000097:blood* / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy*; D016037:Single-Blind Method; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D065127:Dopamine D2 Receptor Antagonists
keywords: Antipsychotics; Dopamine D(2) receptor; Maintenance treatment; Schizophrenia