Predicting Dopamine D2 Receptor Occupancy From Plasma Levels of Antipsychotic Drugs: A Systematic Review and Pooled Analysis
Abstract
Measuring dopamine D₂ receptor occupancy levels using positron emission tomography (PET) is still widely unavailable. The objective of this study was to evaluate the accuracy of predicting D2 occupancy from the antipsychotic plasma level in patients with schizophrenia. Positron emission tomographic studies that measured plasma levels of antipsychotics and their corresponding D₂ occupancy levels were identified, using MEDLINE and EMBASE (last search: March 2010). Antipsychotics that were investigated in a total of 20 subjects or more were included. All data points for each antipsychotic were fit to a one-site binding model to estimate the total plasma concentration of each antipsychotic associated with a 50% occupancy (ED₅₀) of brain D₂ receptors. The mean prediction error and the root mean squared prediction error were used to measure the predictive performance of individual D₂ receptor occupancies from plasma drug levels derived from a one-site occupancy model using an ED₅₀ value calculated for each data point. A total of 34 treatment arms from 23 studies involving 281 subjects were included. The mean (95% confidence interval) prediction errors and root squared prediction errors were as low as 0.0 (-1.8 to 1.8) and 8.9 (7.6-10.2) for risperidone (n = 98); 0.0 (-3.5 to 3.5) and 15.1 (12.9-17.3) for clozapine (n = 75); -0.1 (-1.2 to 1.2), 0.0 (-1.9 to 1.9), and 4.6 (3.5-5.8) for olanzapine (n = 42); 0.1 (-3.4 to 3.5) and 9.9 (7.3-12.5) for haloperidol (n = 35); and -0.1 (-3.3 to 3.1) and 12.3 (8.8-15.7) for ziprasidone (n = 31), respectively. These findings suggest that D₂ occupancy of antipsychotics could be estimated with a high degree of accuracy using widely available plasma levels.
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Clozapine acts partly through non-dopaminergic pathways and demonstrates the lowest correlation between plasma levels and D2 occupancy of commonly used antipsychotics.
“This limitation may apply particularly to clozapine because it acts partly through non-dopaminergic? pathways, and it demonstrates the lowest correlation between plasma levels and D2 occupancy of commonly used antipsychotics.110,112”
From A Method for Tapering Antipsychotic Treatment That May Minimize the Risk of Relapse (2021) · cites this paper as [112]
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- Authors
- Uchida, H., Takeuchi, H., Graff-Guerrero, A., Suzuki, T., Watanabe, K., & Mamo, D. C.
- Affiliations
- Centre for Addiction and Mental Health (CA)
- Keio University (JP)
- Corresponding author
- Uchida, Hiroyuki
- Takeuchi, Hiroyoshi
- Watanabe, Koichiro
- Venue
- Journal of Clinical Psychopharmacology
- Published
- 2011-06
- Volume
- 31
- Issue
- 3
- Pages
- 318-325
- ISSN
- 0271-0749 (ISSN-L)
- OpenAlex
- W2332274857
- Cited by
- 94
- References
- 42
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 5 · 2023: 1 · 2022: 5 · 2021: 11 · 2020: 2 · 2019: 7 · 2018: 4 · 2017: 4 · 2016: 5 · 2015: 7 · 2014: 8 · 2013: 12 · 2012: 10
- FWCI
- 1.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eli Lilly and Company
- Pfizer Health Research Foundation
- Dainippon Sumitomo Pharma
- Astellas Pharma
- Otsuka Pharmaceutical
- Japan Society for the Promotion of Science (22791140)
- Janssen Pharmaceuticals
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- dopamine D2 receptor occupancy, antipsychotic drugs, plasma drug concentration, schizophrenia, ED50, risperidone, clozapine, olanzapine, haloperidol, ziprasidone, pharmacokinetic-pharmacodynamic relationship, prediction error
- MeSH terms
- Brain, Humans, Models, Biological, Antipsychotic Agents, Positron-Emission Tomography, Dopamine D2 Receptor Antagonists
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