Dose reduction of risperidone and olanzapine and estimated dopamine D2 receptor occupancy in stable patients with schizophrenia: Findings from an open-label, randomized, controlled study

Hiroyoshi Takeuchi, Takefumi Suzuki, Robert R. Bies, Gary Remington, Koichiro Watanabe, Masaru Mimura, Hiroyuki Uchida

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Background: While acute-phase antipsychotic response has been attributed to 65%-80% dopamine D<inf>2</inf> receptor blockade, the degree of occupancy for relapse prevention in the maintenance treatment of schizophrenia remains unknown. Method: In this secondary study of an open-label, 28-week, randomized, controlled trial conducted between April 2009 and August 2011, clinically stable patients with schizophrenia (DSM-IV) treated with risperidone or olanzapine were randomly assigned to the reduction group (dose reduced by 50%) or maintenance group (dose kept constant). Plasma antipsychotic concentrations at peak and trough before and after dose reduction were estimated with population pharmacokinetic techniques, using 2 collected plasma samples. Corresponding dopamine D<inf>2</inf> occupancy levels were then estimated using the model we developed. Relapse was defined as worsening in 4 Positive and Negative Syndrome Scale-Positive subscale items: delusion, conceptual disorganization, hallucinatory behavior, and suspiciousness. Results: Plasma antipsychotic concentrations were available for 16 and 15 patients in the reduction and maintenance groups, respectively. Estimated dopamine D<inf>2</inf> occupancy (mean ± SD) decreased following dose reduction from 75.6% ± 4.9% to 66.8% ± 6.4% at peak and 72.3% ± 5.7% to 62.0% ± 6.8% at trough. In the reduction group, 10 patients (62.5%) did not demonstrate continuous D<inf>2</inf> receptor blockade above 65% (ie, < 65% at trough) after dose reduction; furthermore, 7 patients (43.8%) did not achieve a threshold of 65% occupancy even at peak. Nonetheless, only 1 patient met our relapse criteria after dose reduction during the 6 months of the study. Conclusions: The results suggest that the therapeutic threshold regarding dopamine D<inf>2</inf> occupancy may be lower for those who are stable in antipsychotic maintenance versus acute-phase treatment. Positron emission tomography studies are warranted to further test our preliminary findings.

Original languageEnglish (US)
Pages (from-to)1209-1214
Number of pages6
JournalJournal of Clinical Psychiatry
Volume75
Issue number11
DOIs
StatePublished - Nov 1 2014

ASJC Scopus subject areas

  • Psychiatry and Mental health

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