老年精神分裂症患者高催乳素血症的多巴胺D2/3受体占有率阈值
Threshold of Dopamine D2/3 Receptor Occupancy for Hyperprolactinemia in Older Patients With Schizophrenia.
作者信息
Iwata Yusuke, Nakajima Shinichiro, Caravaggio Fernando, Suzuki Takefumi, Uchida Hiroyuki, Plitman Eric, Chung Jun Ku, Mar Wanna, Gerretsen Philip, Pollock Bruce G, Mulsant Benoit H, Rajji Tarek K, Mamo David C, Graff-Guerrero Ariel
机构信息
Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Canada.
Department of Psychiatry, University of Toronto, Toronto, Canada.
出版信息
J Clin Psychiatry. 2016 Dec;77(12):e1557-e1563. doi: 10.4088/JCP.15m10538.
OBJECTIVE
Although hyperprolactinemia carries a long-term risk of morbidity, the threshold of dopamine D2/3 receptor (D2/3R) occupancy for hyperprolactinemia has not been investigated in older patients with schizophrenia. Data were taken from a positron emission tomography (PET) study conducted between August 2007 and August 2015. The present post hoc study included 42 clinically stable outpatients with schizophrenia (DSM-IV) (mean ± SD age = 60.2 ± 6.7 years) taking olanzapine or risperidone. Subjects underwent [¹¹C]-raclopride PET scans to measure D2/3R occupancy before and after reducing their dose of antipsychotic by up to 40%. Blood samples were collected before each PET scan to measure prolactin levels.
METHODS
The relationship between prolactin levels and D2/3R occupancy was examined using stepwise linear regression analyses. The D2/3R occupancy thresholds for hyperprolactinemia were explored using Fisher exact tests.
RESULTS
Prolactin levels decreased following dose reduction (mean ± SD = 24.1 ± 30.2 ng/mL to 17.2 ± 15.1 ng/mL; P < .001). Prolactin levels were associated with female gender (β = .32, P = .006, vs male), antipsychotics (β = .23, P = .02, risperidone vs olanzapine), and D2/3R occupancy (β = .23, P = .04). Those with D2/3R occupancy of 66% or higher were more likely to have hyperprolactinemia than those with D2/3R occupancy lower than 66% (P = .03). Sensitivity, specificity, positive predictive value, and negative predictive value of this threshold were 0.44, 0.81, 0.78, and 0.48, respectively. We identified a D2/3R occupancy threshold for hyperprolactinemia of 66% in older patients with schizophrenia, which is lower than that reported in younger patients (73%) by other researchers.
CONCLUSIONS
Our results suggest a higher sensitivity to antipsychotics in older patients. Prolactin levels could assist in the determination of appropriate antipsychotic dosing to minimize adverse effects.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT00716755.
目的
尽管高催乳素血症存在长期发病风险，但尚未在老年精神分裂症患者中研究高催乳素血症的多巴胺D2/3受体（D2/3R）占有率阈值。数据取自2007年8月至2015年8月进行的一项正电子发射断层扫描（PET）研究。本事后分析研究纳入了42例临床稳定的精神分裂症（DSM-IV）门诊患者（平均±标准差年龄=60.2±6.7岁），他们正在服用奥氮平或利培酮。受试者接受[¹¹C] - 雷氯必利PET扫描，以测量将抗精神病药物剂量降低多达40%前后的D2/3R占有率。在每次PET扫描前采集血样以测量催乳素水平。
方法
使用逐步线性回归分析检查催乳素水平与D2/3R占有率之间的关系。使用Fisher精确检验探索高催乳素血症的D2/3R占有率阈值。
结果
剂量降低后催乳素水平下降（平均±标准差=24.1±30.2 ng/mL降至17.2±15.1 ng/mL；P <.001）。催乳素水平与女性性别（β=.32，P=.006，与男性相比）、抗精神病药物（β=.23，P=.02，利培酮与奥氮平相比）和D2/3R占有率（β=.23，P=.04）相关。D2/3R占有率为66%或更高的患者比D2/3R占有率低于66%的患者更有可能发生高催乳素血症（P=.03）。该阈值的敏感性、特异性、阳性预测值和阴性预测值分别为0.44、0.81、0.78和0.48。我们确定老年精神分裂症患者高催乳素血症的D2/3R占有率阈值为66%，低于其他研究人员报告的年轻患者（73%）的阈值。
结论
我们的结果表明老年患者对抗精神病药物的敏感性更高。催乳素水平有助于确定合适的抗精神病药物剂量，以尽量减少不良反应。
试验注册
ClinicalTrials.gov标识符：NCT00716755。
Zotero 插件