TY - JOUR
T1 - Hyperprolactinemia and estimated dopamine D2 receptor occupancy in patients with schizophrenia
T2 - Analysis of the CATIE data
AU - Tsuboi, Takashi
AU - Bies, Robert R.
AU - Suzuki, Takefumi
AU - Mamo, David C.
AU - Pollock, Bruce G.
AU - Graff-Guerrero, Ariel
AU - Mimura, Masaru
AU - Uchida, Hiroyuki
N1 - Funding Information:
Dr. Tsuboi has received manuscript fees from Dainippon Sumitomo Pharma and speaker's honoraria from Otsuka Pharmaceutical, Eli Lilly and Tsumura within the past two years. Dr. Bies has received NIH, CAMH, Lilly and Indiana University based grant funding. Dr. Suzuki has received manuscript fees or speaker's honoraria from Dainippon Sumitomo Pharma, Eli Lilly, Astellas Pharma, Novartis Pharma, and Meiji Seika Pharma within the past two years. Dr. Pollock receives research support from the National Institute of Health and the Canadian Institutes of Health Research. Within the past five 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 served one time as a consultant for Wyeth (October 2008). He was also a faculty member of the Lundbeck International Neuroscience Foundation (LINF) (final meeting was April 2010). Dr. Graff receives grant support from National Institute of Health, Canadian Institute of Health Research, Ontario Mental Health Foundation, CONACyT, ICyTDF and Janssen. He has served as consultant for Abbott Laboratories, Gedeon Richter Plc, and Eli Lilly within the past two 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 two years. Dr. Uchida has received grants from Pfizer, Astellas Pharmaceutical, Eisai, Otsuka Pharmaceutical, GlaxoSmithKline, Shiohogi, and Dainippon-Sumitomo Pharma, Eli Lilly, Mochida Pharmaceutical, Meiji-Seika Pharma, Janssen Pharmaceutical, and Yoshitomi Yakuhin and speaker's honoraria from Otsuka Pharmaceutical, Janssen Pharmaceutical, Novartis Pharma, Eli Lilly, Shionogi, GlaxoSmithKline, Yoshitomi Yakuhin, Dainippon-Sumitomo Pharma, and Janssen Pharmaceutical within the past two years.
Funding Information:
Data used in the preparation of this article were obtained from the limited access datasets distributed from the NIH-supported “Clinical Antipsychotic Trials of Intervention Effectiveness in Schizophrenia” (CATIE-Sz). This is a multisite, clinical trial of persons with schizophrenia, comparing the effectiveness of randomly assigned medication treatment. The study was supported by NIMH Contract # N01MH90001 to the University of North Carolina at Chapel Hill. The ClinicalTrials.gov identifier is NCT00014001. The version of the dataset used was 1.0. This study was also supported by grant R01MH064173 from the National Institute of Mental Health and was ancillary to Clinical Antipsychotic Trials of Intervention Effectiveness, N01MH90001 , from the National Institute of Mental Health.
PY - 2013/8/1
Y1 - 2013/8/1
N2 - Background: Large-scale data are still lacking on the relationship between serum prolactin concentration and dopamine D2 receptor occupancy in patients with schizophrenia treated with antipsychotics. Methods: The dataset from 481 subjects (risperidone, N = 172, olanzapine, N= 211, and ziprasidone, N = 98) who participated in Phase 1 of the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) was used in the present analysis. Dopamine D2 receptor occupancy levels on the day of the measurement of serum prolactin level were estimated from plasma antipsychotic concentrations. A multivariate general linear model was used to examine effects of clinical and demographic characteristics, including estimated D2 occupancy levels, on serum prolactin concentrations. Individual subjects were divided into two groups, stratified by the presence of hyperprolactinemia. To evaluate the performance of this binary classification, sensitivity, specificity, and accuracy of consecutive cut-off points in the D2 occupancy were calculated. Results: The multivariate general linear model revealed that estimated D2 occupancy levels had significant effects on serum prolactin concentrations while any other variables failed to show significant effects. The cut-off point associated with 0.5 or greater, in both sensitivity and specificity with the greatest accuracy, was 73% (sensitivity, 0.58; specificity, 0.68; accuracy = 0.64) (68-70% for risperidone, 77% for olanzapine, and 55% for ziprasidone.). Conclusion: The threshold for hyperprolactinemia in D2 occupancy may lie somewhat on a lower side of the established therapeutic window with antipsychotics (i.e. 65-80%). This finding highlights the need for the use of the lowest possible dose to avoid this hormonal side effect in the treatment of schizophrenia.
AB - Background: Large-scale data are still lacking on the relationship between serum prolactin concentration and dopamine D2 receptor occupancy in patients with schizophrenia treated with antipsychotics. Methods: The dataset from 481 subjects (risperidone, N = 172, olanzapine, N= 211, and ziprasidone, N = 98) who participated in Phase 1 of the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) was used in the present analysis. Dopamine D2 receptor occupancy levels on the day of the measurement of serum prolactin level were estimated from plasma antipsychotic concentrations. A multivariate general linear model was used to examine effects of clinical and demographic characteristics, including estimated D2 occupancy levels, on serum prolactin concentrations. Individual subjects were divided into two groups, stratified by the presence of hyperprolactinemia. To evaluate the performance of this binary classification, sensitivity, specificity, and accuracy of consecutive cut-off points in the D2 occupancy were calculated. Results: The multivariate general linear model revealed that estimated D2 occupancy levels had significant effects on serum prolactin concentrations while any other variables failed to show significant effects. The cut-off point associated with 0.5 or greater, in both sensitivity and specificity with the greatest accuracy, was 73% (sensitivity, 0.58; specificity, 0.68; accuracy = 0.64) (68-70% for risperidone, 77% for olanzapine, and 55% for ziprasidone.). Conclusion: The threshold for hyperprolactinemia in D2 occupancy may lie somewhat on a lower side of the established therapeutic window with antipsychotics (i.e. 65-80%). This finding highlights the need for the use of the lowest possible dose to avoid this hormonal side effect in the treatment of schizophrenia.
KW - CATIE
KW - Dopamine D2 receptor occupancy
KW - Hyperprolactinemia
KW - Schizophrenia
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U2 - 10.1016/j.pnpbp.2013.05.010
DO - 10.1016/j.pnpbp.2013.05.010
M3 - Article
C2 - 23727135
AN - SCOPUS:84879330939
VL - 45
SP - 178
EP - 182
JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry
JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry
SN - 0278-5846
ER -