ArticleSchizophrenia bulletin2016
Dopamine D2/3 Receptor Occupancy Following Dose Reduction Is Predictable With Minimal Plasma Antipsychotic Concentrations: An Open-Label Clinical Trial.
Article in Schizophrenia bulletin, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
8 citing papers in PubMed, 2 syntheses or guidelines pooled it, 20 citations in OpenAlex.
- EANM perspective on clinical PET and SPECT imaging in schizophrenia-spectrum disorders: a systematic review of longitudinal studies.European journal of nuclear medicine and molecular imaging · 2025Pooled it
- Increasing antipsychotic dose for non response in schizophrenia.The Cochrane database of systematic reviews · 2018Pooled it
- Associations of neuromelanin in the substantia nigra with antipsychotic response in schizophrenia.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Therapeutic Drug Monitoring in Psychiatry: Enhancing Treatment Precision and Patient Outcomes.Pharmaceuticals (Basel, Switzerland) · 2024Review
- MAP Bayesian modelling combining striatal dopamine receptor occupancy and plasma concentrations to optimize antipsychotic dose regimens in individual patients.British journal of clinical pharmacology · 2022Article
- Future Prospects of Positron Emission Tomography-Magnetic Resonance Imaging Hybrid Systems and Applications in Psychiatric Disorders.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Review of Pharmacokinetics and Pharmacogenetics in Atypical Long-Acting Injectable Antipsychotics.Pharmaceutics · 2021Review
- Dopamine D2 -141C Ins/Del and Taq1A polymorphisms, body mass index, and prediction error brain response.Translational psychiatry · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundPopulation pharmacokinetics can predict antipsychotic blood concentrations at a given time point prior to a dosage change. Those predicted blood concentrations could be used to estimate the corresponding dopamine D2/3 receptors (D2/3R) occupancy by antipsychotics based on the tight relationship between blood and brain pharmacokinetics. However, this 2-step prediction has never been tested.
methodsTwo blood samples were collected at separate time points from 32 clinically stable outpatients with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; mean ± SD age: 60.1 ± 7.3 years) to measure plasma concentrations of olanzapine or risperidone at baseline. Then, subjects underwent a dose reduction of olanzapine or risperidone and completed a [(11)C]-raclopride positron emission tomography scan to measure D2/3R occupancy in the putamen. The plasma concentration at the time of the scan was predicted with the 2 samples based on population pharmacokinetic model, using NONMEM. D2/3R occupancy was then estimated by incorporating the predicted plasma concentration in a hyperbole saturation model. The predicted occupancy was compared to the observed value.
resultsThe mean (95% CI) prediction errors for the prediction of D2/3R occupancy were -1.76% (-5.11 to 1.58) for olanzapine and 0.64% (-6.18 to 7.46) for risperidone. The observed and predicted D2/3R occupancy levels were highly correlated (r = 0.67, P = .001 for olanzapine; r = 0.67, P = .02 for risperidone).
conclusionsD2/3R occupancy levels can be predicted from blood drug concentrations collected prior to dosage change. Although this 2-step model is subject to a small degree of error, it could be used to select oral doses aimed at achieving optimal D2/3R occupancy on an individual basis.
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