A Cross-Sectional Study of Plasma Risperidone Levels With Risperidone Long-Acting Injectable: Implications for Dopamine D2 Receptor Occupancy During Maintenance Treatment in Schizophrenia
A Cross-Sectional Study of Plasma Risperidone Levels With Risperidone Long-Acting Injectable: Implications for Dopamine D2 Receptor Occupancy During Maintenance Treatment in Schizophrenia
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DOI：
10.4088/jcp.12m07638
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发表时间：
2012-08-01
影响因子：
5.3
通讯作者：
Uchida, Hiroyuki
中科院分区：
文献类型：
--
作者：
Ikai, Saeko;Remington, Gary;Uchida, Hiroyuki
目的：虽然已经提出在精神分裂症的急性治疗期间，抗精神病药的多巴胺D-2受体的65%-80%占据率达到最佳治疗反应，但仍不清楚是否也有必要将D-2受体占据率维持在持续维持治疗的“安全”窗口内。数据是特别稀缺的长效抗精神病formulation.Method：临床稳定的精神分裂症患者（DSM-IV）接受稳定剂量的利培酮长效注射剂（LAI）作为抗精神病药物单药治疗至少3个月，并在过去的6个月内，任何精神科住院治疗。根据肌内注射利培酮LAI前即刻利培酮+9-羟基利培酮的血浆浓度，使用源自我们先前正电子发射断层扫描数据的1-位点结合模型，估计谷值时多巴胺D-2受体结合水平。结果：36例患者（平均年龄49.3 ± 14.0岁，平均剂量38.2 ± 11.6 mg，平均间隔16.5 ± 14.0 d）入组。平均SD D-2受体结合率为62.1% +/- 15.4%; 52.8%的受试者（n =19）未显示结合率65%。另一方面，13.9%（n = 5）显示D-2占用高达超过80%at the estimated tough.Conclusions：超过一半的患者服用利培酮LA 1保持临床稳定，而没有实现多巴胺D-2受体的连续阻断>= 65%，在现实世界的临床设置。结果表明，持续的多巴胺D-2受体占用水平>= 65%可能不是必要的维持治疗与利培酮LAI精神分裂症。J Clin Psychiatry 2012;73（8）：1147-1152（c）版权所有2012 Physicians Postgraduate Press，Inc.
Objective: While 65%-80% occupancy of dopamine D-2 receptors with antipsychotics has been proposed to achieve optimal therapeutic response during acute treatment of schizophrenia, it remains unclear as to whether it is also necessary to maintain, D-2 receptor occupancy within this "safe" window for ongoing maintenance treatment. The data are especially scarce for long-acting antipsychotic formulations.Method: Clinically stable patients with schizophrenia (DSM-IV) receiving a stable dose of risperidone long-acting injectable (LAI) as antipsychotic monotherapy for at least 3 months and free of any psychiatric hospitalization over the past 6 months were included. Dopamine D-2 receptor occupancy levels at trough were estimated from plasma concentrations of risperidone plus 9-hydroxyrisperidone immediately before the intramuscular injection of risperidone LAI, using a 1-site binding model derived from our previous positron emission tomography data. This study was conducted from October to December 2011.Results: 36 patients were included in this study (mean +/- SD age, 49.3 +/- 14.0 years; mean SD dose and interval of injections, 38.2 +/- 11.6 mg and 16.5 +/- 14.0 days, respectively). Mean SD D-2 receptor occupancy was 62.1% +/- 15.4%; 52.8% of the subjects (n =19) did not demonstrate an occupancy of 65%. On the other hand, 13.9% (n = 5) showed a D-2 occupancy as high as over 80% at the estimated trough.Conclusions: More than half of patients taking risperidone LAl maintained clinical stability without achieving continuous blockade of dopamine D-2 receptors >= 65% in real-world clinical settings. Results suggest that sustained dopamine D-2 receptor occupancy levels of >= 65% may not be necessary for maintenance treatment with risperidone LAI in schizophrenia. J Clin Psychiatry 2012;73(8):1147-1152 (c) Copyright 2012 Physicians Postgraduate Press, Inc.