Hyperprolactinemia and estimated dopamine D2 receptor occupancy in patients with schizophrenia: analysis of the CATIE data.
Hyperprolactinemia and estimated dopamine D2 receptor occupancy in patients with schizophrenia: analysis of the CATIE data.
复制标题
精神分裂症患者的高催乳素血症和估计的多巴胺 D2 受体占用率：CATIE 数据分析。
DOI：
10.1016/j.pnpbp.2013.05.010
复制
发表时间：
2013
影响因子：
5.6
通讯作者：
Uchida,Hiroyuki
中科院分区：
文献类型：
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作者：
Tsuboi,Takashi;Bies,RobertR;Suzuki,Takefumi;Mamo,DavidC;Pollock,BruceG;Graff-Guerrero,Ariel;Mimura,Masaru;Uchida,Hiroyuki
背景：目前尚缺乏关于抗精神病药物治疗的精神分裂症患者血清催乳素浓度与多巴胺D2受体结合率之间关系的大规模数据。（利培酮，N = 172，奥氮平，N = 211，齐拉西酮，N = 98），参加了干预有效性临床抗精神病药物试验（CATIE）的1期研究。根据血浆抗精神病药物浓度估计血清催乳素水平测量当天的多巴胺D2受体占用水平。采用多变量一般线性模型研究临床和人口统计学特征（包括估计的D2占用水平）对血清催乳素浓度的影响。个体受试者分为两组，根据是否存在高泌乳素血症分层。为了评估这种二元分类的性能，灵敏度，特异性和连续的截止点在D2 occupancy.ResultsThe多元一般线性模型计算的准确性，估计D2的占用水平有显着影响血清催乳素浓度，而任何其他变量未能显示出显着的影响。敏感性和特异性均大于等于0.5且准确性最高的临界点为73%（敏感性为0.58;特异性为0.68;准确性= 0.64）（利培酮为68-70%，奥氮平为77%，齐拉西酮为55%）。结论高泌乳素血症在D2期的阈值可能略低于抗精神病药物治疗窗（65-80%）。这一发现强调了在治疗精神分裂症时需要使用尽可能低的剂量以避免这种激素副作用。
BackgroundLarge-scale data are still lacking on the relationship between serum prolactin concentration and dopamine D2 receptor occupancy in patients with schizophrenia treated with antipsychotics.MethodsThe 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.ResultsThe 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.).ConclusionThe 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.