Therapeutic Window for Striatal Dopamine D2/3 Receptor Occupancy in Older Patients with Schizophrenia: A Pilot PET Study
Therapeutic Window for Striatal Dopamine D2/3 Receptor Occupancy in Older Patients with Schizophrenia: A Pilot PET Study
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DOI：
10.1016/j.jagp.2013.01.045
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发表时间：
2014-10-01
影响因子：
7.2
通讯作者：
Mamo, David C.
中科院分区：
文献类型：
--
作者：
Uchida, Hiroyuki;Suzuki, Takefumi;Mamo, David C.
目的：在年轻的精神分裂症患者中，正电子发射断层扫描（PET）研究已经确定了纹状体多巴胺D-2/3受体占有率为65%-80%的治疗窗口。这种经验性的信息在晚年是得不到的。我们的主要目的是评估D-2/3相对受体结合率（RRO）的变化对该人群临床结局的影响。设计：开放标签干预。单位：成瘾和心理健康中心，多伦多。参会人员：年龄≥ 50岁、临床稳定且既往口服利培酮超过6个月的精神分裂症受试者。干预：将利培酮剂量减少40%，随后进行3个月的随访。测量值：在剂量降低之前和之后，使用[C-11]雷氯必利PET扫描的感兴趣区域分析评估背壳核中的多巴胺D2/3 RRO。临床评估包括阳性和阴性综合征量表和辛普森-安格斯量表。结果：9名受试者（平均+/- SD年龄：58 +/- 7岁;平均+/- SD基线利培酮剂量：3.4 +/- 1.6 mg/天）参加了研究。6例受试者出现锥体外系症状（EPS），与壳核中70%或以上的D-2/3 RRO相关（范围：70%-87%）。减量后，5例受试者的EPS消退。2例受试者在52%和小于50% D-2/3 RRO时发生临床恶化。结论：EPS使D-2/3 RRO降低不到70%，提示老年精神分裂症患者的治疗窗较年轻患者低。虽然这些发现必须在更大的样本中重复，但它们对未来的药物开发和老年精神分裂症的临床指南具有重要意义。
Objective: In younger patients with schizophrenia, positron emission tomography (PET) studies have identified a therapeutic window of striatal dopamine D-2/3 receptor occupancy of 65%-80%. This type of empirical information is not available in late life. Our primary aim was to assess the effect of changes in D-2/3 relative receptor occupancy (RRO) on clinical outcomes in this population. Design: Open-label intervention. Setting: Centre for Addiction and Mental Health, Toronto. Participants: Subjects with schizophrenia age 50 years or more who were clinically stable and previously maintained on oral risperidone for more than 6 months. Intervention: A dose reduction of risperidone of up to 40%, followed by a 3-month follow-up. Measurements: Dopamine D2/3 RRO in dorsal putamen was assessed, using the region of interest analysis of [C-11] raclopride PET scans, before and after the dose reduction. Clinical assessments included the Positive and Negative Syndrome Scale and the Simpson-Angus Scale. Results: Nine subjects (mean +/- SD age: 58 +/- 7 years; mean +/- SD baseline risperidone dose: 3.4 +/- 1.6 mg/day) participated in the study. Extrapyramidal symptoms (EPS) were present in six subjects and were associated with 70% or more D-2/3 RRO in the putamen (range: 70%-87%). Following the dose reduction, EPS resolved in five subjects. Two subjects experienced a clinical worsening at 52% and at less than 50% D-2/3 RRO. Conclusion: EPS diminished less than 70% D-2/3 RRO, which suggests a lower therapeutic window for older patients with schizophrenia than that for younger patients. Although these findings have to be replicated in a larger sample, they have important implications for future drug development and clinical guidelines in late-life schizophrenia.