Dopamine D2 Receptor Occupancy and Clinical Effects
- 1 August 2011
- journal article
- review article
- Published by Ovid Technologies (Wolters Kluwer Health) in Journal of Clinical Psychopharmacology
- Vol. 31 (4), 497-502
- https://doi.org/10.1097/jcp.0b013e3182214aad
Abstract
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.Keywords
This publication has 43 references indexed in Scilit:
- Predicting Dopamine D2 Receptor Occupancy From Plasma Levels of Antipsychotic DrugsJournal of Clinical Psychopharmacology, 2011
- D2 Receptor Blockade by Risperidone Correlates With Attention Deficits in Late-Life SchizophreniaJournal of Clinical Psychopharmacology, 2009
- Striatal D2/D3 Receptor Occupancy, Clinical Response and Side Effects with Amisulpride: An Iodine-123-Iodobenzamide SPET StudyPharmacopsychiatry, 2008
- Cortical Dopamine D2/D3 Receptors Are a Common Site of Action for Antipsychotic Drugs--An Original Patient Data Meta-analysis of the SPECT and PET In Vivo Receptor Imaging LiteratureSchizophrenia Bulletin, 2008
- D2 Receptor Occupancy of Olanzapine Pamoate Depot Using Positron Emission Tomography: An Open-label Study in Patients with SchizophreniaNeuropsychopharmacology, 2007
- Establishing a dose-response relationship for oral risperidone in relapsed schizophreniaJournal of Psychopharmacology, 2005
- Complete Dopamine D2 Receptor Occupancy Without Extrapyramidal Side Effects Under BenperidolJournal of Clinical Psychopharmacology, 2004
- A Multidose Study of Haloperidol Decanoate in the Maintenance Treatment of SchizophreniaAmerican Journal of Psychiatry, 2002
- Do Loxapine Plus Cyproheptadine Make an Atypical Antipsychotic? PET Analysis of Their Dopamine D2 and Serotonin2 Receptor OccupancyArchives of General Psychiatry, 1998
- A RATING SCALE FOR EXTRAPYRAMIDAL SIDE EFFECTSActa Psychiatrica Scandinavica, 1970