Challenging the need for sustained blockade of dopamine D<inf>2</inf> receptor estimated from antipsychotic plasma levels in the maintenance treatment of schizophrenia

A single-blind, randomized, controlled study

Takashi Tsuboi, Takefumi Suzuki, Robert Bies, Gary Remington, Bruce G. Pollock, Masaru Mimura, Hiroyuki Uchida

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Objective: Blockade of dopamine D<inf>2</inf> 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. Method: In this single-blind, 52-week, randomized controlled trial, clinically stable patients with schizophrenia receiving risperidone or olanzapine were randomly assigned to the continuous D<inf>2</inf> blockade (i.e. an estimated trough D<inf>2</inf> 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. Conclusion: These results offer support that the threshold for D<inf>2</inf> 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.

Original languageEnglish
Pages (from-to)149-154
Number of pages6
JournalSchizophrenia Research
Volume164
Issue number1-3
DOIs
StatePublished - May 1 2015

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Dopamine D2 Receptors
Antipsychotic Agents
Schizophrenia
olanzapine
Single-Blind Method
Risperidone
Therapeutics
Randomized Controlled Trials

Keywords

  • Antipsychotics
  • Dopamine D<inf>2</inf> receptor
  • Maintenance treatment
  • Schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Challenging the need for sustained blockade of dopamine D<inf>2</inf> receptor estimated from antipsychotic plasma levels in the maintenance treatment of schizophrenia : A single-blind, randomized, controlled study. / Tsuboi, Takashi; Suzuki, Takefumi; Bies, Robert; Remington, Gary; Pollock, Bruce G.; Mimura, Masaru; Uchida, Hiroyuki.

In: Schizophrenia Research, Vol. 164, No. 1-3, 01.05.2015, p. 149-154.

Research output: Contribution to journalArticle

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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. Method: 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. Conclusion: 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.",
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