期刊
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
卷 31, 期 4, 页码 497-502出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/JCP.0b013e3182214aad
关键词
antipsychotic; dopamine; dopamine D-2 receptor; positron emission tomography; schizophrenia
资金
- Japan Research Foundation for Clinical Pharmacology
- Inokashira Hospital
- Ministry of Education, Culture, Sports, Science and Technology
- Japanese Society of Clinical Neuropsychopharmacology
- Mochida Memorial Foundation
- Government of Canada
- Kanae Foundation
- Pfizer Health Research Foundation
- GlaxoSmithKline
- Otsuka Pharmaceutical
- Dainippon Sumitomo Pharma
- Janssen Pharmaceutical
- Pfizer
- Eli Lilly
- Abbott
- Janssen
- Forest Laboratories
- Lilly
- Astellas Pharma
Positron emission tomography (PET) studies proposed a therapeutic window of D-2 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 D-2 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 D-2 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% D-2 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.
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