Reeves Suzanne, Eggleston Kate, Cort Elizabeth, McLachlan Emma, Brownings Stuart, Nair Akshay, Greaves Suki, Smith Alan, Dunn Joel, Marsden Paul, Kessler Robert, Taylor David, Bertrand Julie, Howard Robert
Division of Psychiatry, University College London, UK.
Department of Old Age Psychiatry, Kings College London, UK.
Int J Geriatr Psychiatry. 2018 Feb;33(2):396-404. doi: 10.1002/gps.4758. Epub 2017 Jun 23.
Antipsychotic drug sensitivity in very late-onset schizophrenia-like psychosis (VLOSLP) is well documented, but poorly understood. This study aimed to investigate blood drug concentration, D2/3 receptor occupancy and outcome in VLOSLP during open amisulpride prescribing, and compare this with Alzheimer's disease (AD).
Blood drug concentration, prolactin, symptoms and extrapyramidal side-effects (EPS) were serially assessed during dose titration. [ F]fallypride imaging was used to quantify D2/3 receptor occupancy. Average steady-state amisulpride concentration (Caverage, ng/ml) was estimated by incorporating pharmacokinetic (PK) data into an existing population PK model (25 AD participants, 20 healthy older people).
Eight patients (target 20) were recruited (six women; 76 + - 6 years; six treatment compliant; five serially sampled; three with paired imaging data). Mean + - SD symptom reduction was 74 ± 12% (50-100 mg/day; 92.5 + -39.4 ng/ml). Mild EPS emerged at 96 ng/ml (in AD, severe EPS, 50 mg/day, 60 ng/ml). In three participants, imaged during optimal treatment (50 mg/day; 41-70 ng/ml), caudate occupancy was 44-59% (58-74% in AD across a comparable Caverage).
Despite the small sample size, our findings are highly relevant as they suggest that, as in AD, 50 mg/day amisulpride is associated with >40% occupancy and clinically relevant responses in VLOSLP. It was not possible to fully characterise concentration-occupancy relationships in VLOSLP, and it is thus unclear whether the greater susceptibility of those with AD to emergent EPS was accounted for by increased central drug access. Further investigation of age- and diagnosis-specific threshold sensitivities is warranted, to guide amisulpride prescribing in older people, and therapeutic drug monitoring studies offer a potentially informative future approach. Copyright © 2017 John Wiley & Sons, Ltd.
超晚发性精神分裂症样精神病（VLOSLP）对抗精神病药物的敏感性已有充分记录，但了解甚少。本研究旨在调查开放处方氨磺必利期间VLOSLP患者的血药浓度、D2/3受体占有率及治疗结果，并与阿尔茨海默病（AD）进行比较。
在剂量滴定期间连续评估血药浓度、催乳素、症状及锥体外系副作用（EPS）。使用[F]氟哌利多成像定量D2/3受体占有率。通过将药代动力学（PK）数据纳入现有的群体PK模型（25名AD参与者，20名健康老年人）来估计氨磺必利的平均稳态浓度（Caverage，ng/ml）。
招募了8名患者（目标为20名）（6名女性；76±6岁；6名依从治疗；5名进行了连续采样；3名有配对成像数据）。症状平均减轻74±12%（50 - 100mg/天；92.5±39.4ng/ml）。血药浓度为96ng/ml时出现轻度EPS（在AD中，血药浓度为60ng/ml、剂量为50mg/天时出现严重EPS）。在3名处于最佳治疗阶段（50mg/天；41 - 70ng/ml）的参与者中，尾状核占有率为44 - 59%（在AD中，在可比的Caverage水平下，尾状核占有率为58 - 74%）。
尽管样本量较小，但我们的研究结果具有高度相关性，因为它们表明，与AD一样，每天50mg氨磺必利与VLOSLP中>40%的占有率及临床相关反应相关。在VLOSLP中无法完全表征浓度 - 占有率关系，因此尚不清楚AD患者对新发EPS更敏感是否是由于中枢药物可达性增加所致。有必要进一步研究年龄和诊断特异性阈值敏感性，以指导老年人氨磺必利的处方，治疗药物监测研究提供了一种可能具有信息价值的未来方法。版权所有© 2017约翰威立父子有限公司。
