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.).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsuboi
authors.forename: Robert R
authors.initials: RR
authors.lastname: Bies
authors.forename: Takefumi
authors.initials: T
authors.lastname: Suzuki
authors.forename: David C
authors.initials: DC
authors.lastname: Mamo
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Pollock
authors.forename: Ariel
authors.initials: A
authors.lastname: Graff-Guerrero
authors.forename: Masaru
authors.initials: M
authors.lastname: Mimura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uchida
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000097:blood / Q000494:pharmacology; D001569:Benzodiazepines / Q000009:adverse effects* / Q000097:blood / Q000494:pharmacology; D005260:Female; D006801:Humans; D006966:Hyperprolactinemia / Q000097:blood / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D010879:Piperazines / Q000009:adverse effects* / Q000097:blood / Q000494:pharmacology; D011237:Predictive Value of Tests; D011388:Prolactin / Q000097:blood; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D018967:Risperidone / Q000009:adverse effects* / Q000097:blood / Q000494:pharmacology; D012559:Schizophrenia / Q000097:blood / Q000150:complications / Q000378:metabolism*; D012680:Sensitivity and Specificity; D013844:Thiazoles / Q000009:adverse effects* / Q000097:blood / Q000494:pharmacology
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; D017448:Receptors, Dopamine D2; D013844:Thiazoles; D001569:Benzodiazepines; C092292:ziprasidone; D011388:Prolactin; D018967:Risperidone; D000077152:Olanzapine
keywords: CATIE; Clinical Antipsychotic Trials in Intervention Effectiveness; Dopamine D2 receptor occupancy; Hyperprolactinemia; PET; Schizophrenia; positron emission tomography