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.
RCT Entities:
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.
Authors: Shinichiro Nakajima; Hiroyuki Uchida; Robert R Bies; Fernando Caravaggio; Takefumi Suzuki; Eric Plitman; Wanna Mar; Philip Gerretsen; Bruce G Pollock; Benoit H Mulsant; David C Mamo; Ariel Graff-Guerrero Journal: Schizophr Bull Date: 2015-07-28 Impact factor: 9.306
Authors: Claire H Li; Robert E Stratford; Nieves Velez de Mendizabal; Thomas I F H Cremers; Bruce G Pollock; Benoit H Mulsant; Gary Remington; Robert R Bies Journal: J Transl Med Date: 2014-08-20 Impact factor: 5.531
Authors: Kimberly E Vanover; Robert E Davis; Yun Zhou; Weiguo Ye; James R Brašić; Lorena Gapasin; Jelena Saillard; Michal Weingart; Robert E Litman; Sharon Mates; Dean F Wong Journal: Neuropsychopharmacology Date: 2018-10-26 Impact factor: 7.853
Authors: Marco Solmi; Andrea Murru; Isabella Pacchiarotti; Juan Undurraga; Nicola Veronese; Michele Fornaro; Brendon Stubbs; Francesco Monaco; Eduard Vieta; Mary V Seeman; Christoph U Correll; André F Carvalho Journal: Ther Clin Risk Manag Date: 2017-06-29 Impact factor: 2.423