Dopamine D2 receptor occupancy and clinical effects: A systematic review and pooled analysis

Hiroyuki Uchida, Hiroyoshi Takeuchi, Ariel Graff-Guerrero, Takefumi Suzuki, Koichiro Watanabe, David C. Mamo

研究成果: Review article査読

98 被引用数 (Scopus)

抄録

Positron emission tomography (PET) studies proposed a therapeutic window of D2 receptor occupancy (65%-80%) of antipsychotics for the treatment of schizophrenia in young adults. However, this conclusion has been drawn from clinical PET studies using small sample sizes (<20). Prospective PET studies that measured D2 occupancy levels and assessed extrapyramidal side effects (EPS) and/or treatment response induced by antipsychotics (excluding partial agonists) were identified, using MEDLINE and EMBASE (last search: March 2010). Individual subjects were divided into 2 groups based on EPS status (ie, presence or lack of newly emergent EPS) and treatment response (ie, a ≥ 25% or ≥ 50% reduction in the Positive and Negative Syndrome Scale or Brief Psychiatric Rating Scale). To evaluate the performance of this binary classification, sensitivity, specificity, and accuracy of consecutive cutoff points in the D2 occupancy were calculated: Accuracy = (True Positive + True Negative)/Total N. Twelve studies, including a total of 82 subjects, were included in our analyses. The cutoff points associated with 0.5 or greater in both sensitivity and specificity with the greatest accuracy were 77% to 78% for EPS, 60% for a 25% or greater symptom reduction, and 72% for a 50% or greater symptom reduction. These findings support the presence of a therapeutic window of 60% to 78% D2 occupancy of antipsychotics in young adults with schizophrenia and may suggest the presence of a continuum of effectiveness with increasing occupancy within this therapeutic window.

本文言語English
ページ(範囲)497-502
ページ数6
ジャーナルJournal of clinical psychopharmacology
31
4
DOI
出版ステータスPublished - 2011 8

ASJC Scopus subject areas

  • 精神医学および精神衛生
  • 薬理学(医学)

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