Skip Navigation LinksHome > October 2013 - Volume 33 - Issue 5 > Estimating Dopamine D2 Receptor Occupancy for Doses of 8 Ant...
Journal of Clinical Psychopharmacology:
doi: 10.1097/JCP.0b013e3182983ffa
Review Article

Estimating Dopamine D2 Receptor Occupancy for Doses of 8 Antipsychotics: A Meta-Analysis

Lako, Irene M. PhD*†; van den Heuvel, Edwin R. PhD; Knegtering, Henrikus MD, PhD†§; Bruggeman, Richard MD, PhD*†∥; Taxis, Katja PhD*

Supplemental Author Material
Collapse Box

Abstract

Rationale: Dose equivalents based on dopamine D2 receptor occupancy can be used to compare antipsychotics on D2 receptor-mediated (adverse) effects such as extrapyramidal symptoms and altered emotionalexperiences. Previous meta-analyses modeling the dose-occupancy relationship hardly addressed potential heterogeneity of the imaging data.

Objectives: To model the relationship between dose and D2 receptor occupancy for a series of frequently prescribed antipsychotics while addressing the potential heterogeneity of the imaging data.

Methods: We conducted a meta-analysis on published D2 receptor occupancy data (positron emission tomography and single-photon emission computed tomography) in patients with schizophrenia treated with antipsychotics. A nonlinear mixed effects model estimated the median D2 receptor occupancy for a given antipsychotic dose. Heterogeneity between studies was investigated by incorporating study as a random effect in the model, in addition to patient- and study-specific explanatory variables.

Results: Included were 51 studies, describing 606 patients (mean ± SD age, 32.2 ±10.8 years; 25.7% female). The models described the dose-occupancy relationship with narrow confidence bands around the therapeuticdose range. Maximum occupancy (95% confidence interval[CI]) was estimated for haloperidol (91.9%; 95% CI, 86.1–97.8), risperidone(92.4%; 95% CI, 81.8–100), olanzapine (96.5%; 95% CI,85.8–100), clozapine (61.7%; 95% CI, 49.2–74.2), quetiapine (49.1%; 95% CI, 18.7–79.6), aripiprazole (86.9%; 95% CI, 78.2–95.7), ziprasidone (82.9%; 95% CI, 44.9–100), and amisulpride (85.0%; 95% CI, 68.5–100). Interindividual differences explained most of the variability in occupancy values, besides significant heterogeneity between studies.

Conclusions: Dose-occupancy functions estimated the median level of dopamine D2 receptor occupancy for 8 frequently prescribed antipsychotics in patients with schizophrenia. These dose equivalents can be used to compare antipsychotic effects in epidemiological studies and clinical practice.

© 2013 by Lippincott Williams & Wilkins.

Login

Article Tools

Share

Article Level Metrics

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.