@article{5305c0ed15004ae9b12745601e58c748,
title = "Dopamine D2 receptor occupancy with risperidone or olanzapine during maintenance treatment of schizophrenia: A cross-sectional study",
abstract = "In treating schizophrenia, it has been established that 65-80% occupancy of dopamine D2 receptors optimizes therapeutic efficacy while minimizing risks of extrapyramidal symptoms. However, it is unclear as to whether it is necessary to keep D2 receptor occupancy within this therapeutic window to maintain response. In this study, daily peak and trough D2 receptor occupancy levels were estimated in clinically stable patients with schizophrenia (DSM-IV) who were receiving risperidone or olanzapine. Using two collected plasma samples, plasma antipsychotic concentrations at peak and trough were estimated with population pharmacokinetic techniques. Corresponding dopamine D2 receptor occupancy levels were then estimated, using a recently developed model. 35 subjects with stable schizophrenia completed the study (mean ± SD age, 48.8 ± 13.8. years; male [N = 14]; Asians [N = 23], Caucasians [N = 12]; risperidone [N = 20] at 3.2 ± 2.3. mg/day, and olanzapine [N = 15] at 9.2 ± 4.9. mg/day) between September and December 2010. 48.6% (N = 17) did not achieve a continuous blockade of ≥ 65%. Moreover, 11.4% (N = 4) did not achieve the 65% threshold at estimated peak concentrations. In conclusion, approximately half the subjects with stable schizophrenia did not achieve estimated continuous blockade of D2 receptor occupancy of ≥ 65%. The results suggest that sustained D2 receptor occupancy levels of ≥ 65% may not always be necessary for the maintenance treatment of schizophrenia.",
keywords = "Antipsychotic, Dopamine, Maintenance, Olanzapine, Risperidone, Schizophrenia",
author = "Yuya Mizuno and Bies, {Robert R.} and Gary Remington and Mamo, {David C.} and Takefumi Suzuki and Pollock, {Bruce G.} and Takashi Tsuboi and Koichiro Watanabe and Masaru Mimura and Hiroyuki Uchida",
note = "Funding Information: Dr. Bies has received NIH, CAMH, Lilly and Indiana University based grant funding. Dr. Remington receives research support (Principal Investigator) from the following funding agencies: Schizophrenia Society of Ontario, Canadian Diabetes Association, and Canadian Institutes of Health Research. He also receives research support from the following pharmaceutical companies: Novartis Canada, Medicure Inc., and Neurocrine Bioscience. He has received consultant fees from CanAm Bioresearch Inc., Neurocrine Bioscience Inc., and Roche, as well as speaker's fees from Novartis. He holds no commercial investments in any pharmaceutical company. Dr. Mamo has received investigator-initiated grant support from Pfizer within the past 5 years. Dr Suzuki has received fellowship grants from the Japanese Society of Clinical Neuropsychopharmacology, Government of Canada Post-Doctoral Research Fellowships, Kanae Foundation and Mochida Memorial Foundation, and manuscript fee from Dainippon Sumitomo Pharma and Kyowa Hakko Kirin, and speaker's honoraria from Eli Lilly within the past 5 years. Dr. Pollock receives research support from the National Institute of Health and the Canadian Institutes of Health Research. Within the past 5 years he has been a member of the advisory board of Lundbeck Canada (final meeting was May 2009) and Forest Laboratories (final meeting was March 2008). Dr. Pollock has also served one time as a consultant for Wyeth (October 2008) and Takeda (July 2007). He was also a faculty member of the Lundbeck International Neuroscience Foundation (LINF) (final meeting was April 2010). Dr. Tsuboi has received speaker's honoraria or manuscript fees from Otsuka Pharmaceutical and Dainippon Sumitomo Pharma within the past 5 years. Dr. Watanabe has received grants, or consultant fees from Dainippon Sumitomo Pharma, Eli Lilly, GlaxoSmithKline, Janssen Pharmaceutical, and Pfizer, and received speaker's honoraria from Astellas Pharma, Dainippon Sumitomo Pharma, Eli Lilly, GlaxoSmithKline, Janssen Pharmaceutical, Meiji, Otsuka Pharmaceutical, Pfizer, and Yoshitomi Yakuhin within the past 5 years. Dr. Mimura has received grants, or consultant fees from Eisai, Astellas Pharma, GlaxoSmithKline and Meiji, and received speaker's honoraria from Astellas Pharma, Dainippon Sumitomo Pharma, Eli Lilly, GlaxoSmithKline, Janssen Pharmaceutical, Meiji, Otsuka Pharmaceutical, Pfizer, and Yoshitomiyakuhin within the past 3 years. Dr. Uchida has received grants, speaker's honoraria, or manuscript fees from Pfizer Health Research Foundation, GlaxoSmithKline, Otsuka Pharmaceutical, Dainippon Sumitomo Pharma, Janssen Pharmaceutical, and Pfizer within the past 5 years. Other authors have nothing to disclose. Funding Information: This work was funded by Grant-in-Aid for Young Scientists-B from the Ministry of Education, Culture, Sports, Science and Technology and Japan Research Foundation for Clinical Pharmacology ; these two funding sources had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.",
year = "2012",
month = apr,
day = "27",
doi = "10.1016/j.pnpbp.2011.12.013",
language = "English",
volume = "37",
pages = "182--187",
journal = "Progress in Neuro-Psychopharmacology and Biological Psychiatry",
issn = "0278-5846",
publisher = "Elsevier Inc.",
number = "1",
}