Hyperprolactinemia and estimated dopamine D2 receptor occupancy in patients with schizophrenia: Analysis of the CATIE data

Takashi Tsuboi, Robert Bies, Takefumi Suzuki, David C. Mamo, Bruce G. Pollock, Ariel Graff-Guerrero, Masaru Mimura, Hiroyuki Uchida

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)178-182
Number of pages5
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume45
DOIs
StatePublished - Aug 1 2013

Fingerprint

Hyperprolactinemia
Dopamine D2 Receptors
olanzapine
Prolactin
Antipsychotic Agents
Schizophrenia
Clinical Trials
Risperidone
Serum
Sensitivity and Specificity
Linear Models
Clinical Trials, Phase I
Demography
ziprasidone
Therapeutics

Keywords

  • CATIE
  • Dopamine D2 receptor occupancy
  • Hyperprolactinemia
  • Schizophrenia

ASJC Scopus subject areas

  • Biological Psychiatry
  • Pharmacology

Cite this

Hyperprolactinemia and estimated dopamine D2 receptor occupancy in patients with schizophrenia : Analysis of the CATIE data. / Tsuboi, Takashi; Bies, Robert; Suzuki, Takefumi; Mamo, David C.; Pollock, Bruce G.; Graff-Guerrero, Ariel; Mimura, Masaru; Uchida, Hiroyuki.

In: Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 45, 01.08.2013, p. 178-182.

Research output: Contribution to journalArticle

Tsuboi, Takashi ; Bies, Robert ; Suzuki, Takefumi ; Mamo, David C. ; Pollock, Bruce G. ; Graff-Guerrero, Ariel ; Mimura, Masaru ; Uchida, Hiroyuki. / Hyperprolactinemia and estimated dopamine D2 receptor occupancy in patients with schizophrenia : Analysis of the CATIE data. In: Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2013 ; Vol. 45. pp. 178-182.
@article{cb41283e5e2945ad967e0a584fb1bdcd,
title = "Hyperprolactinemia and estimated dopamine D2 receptor occupancy in patients with schizophrenia: Analysis of the CATIE data",
abstract = "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.",
keywords = "CATIE, Dopamine D2 receptor occupancy, Hyperprolactinemia, Schizophrenia",
author = "Takashi Tsuboi and Robert Bies and Takefumi Suzuki and Mamo, {David C.} and Pollock, {Bruce G.} and Ariel Graff-Guerrero and Masaru Mimura and Hiroyuki Uchida",
year = "2013",
month = "8",
day = "1",
doi = "10.1016/j.pnpbp.2013.05.010",
language = "English",
volume = "45",
pages = "178--182",
journal = "Progress in Neuro-Psychopharmacology and Biological Psychiatry",
issn = "0278-5846",
publisher = "Elsevier Inc.",

}

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

AU - Suzuki, Takefumi

AU - Mamo, David C.

AU - Pollock, Bruce G.

AU - Graff-Guerrero, Ariel

AU - Mimura, Masaru

AU - Uchida, Hiroyuki

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

UR - http://www.scopus.com/inward/record.url?scp=84879330939&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84879330939&partnerID=8YFLogxK

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 -