Suggested minimal effective dose of risperidone based on PET-measured D2 and 5-HT2A receptor occupancy in schizophrenic patients
Suggested minimal effective dose of risperidone based on PET-measured D2 and 5-HT2A receptor occupancy in schizophrenic patients
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DOI：
10.1176/ajp.156.6.869
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发表时间：
1999-06-01
影响因子：
17.7
通讯作者：
Farde, L
中科院分区：
文献类型：
--
作者：
Nyberg, S;Eriksson, B;Farde, L
目的：新型抗精神病药物利培酮的多中心试验建议标准剂量为6mg /天。然而，在固定剂量研究中产生最高反应率的剂量可能超过大多数患者的最小有效剂量。这项正电子发射断层扫描（PET）研究的目的是根据多巴胺D-2和5-羟色胺5-HT2A受体占用率的测量建议利培酮的最小有效剂量。方法：8例首发或无药精神分裂症患者分别给予利培酮6mg /d治疗4周，3mg /d治疗2周。4周和6周后行PET，用[C-11]raclopride测定Dp受体占用率，用[C-11]N-methylspiperone测定5-HT2A受体占用率。结果：7例患者完成研究并对利培酮治疗有反应。在纳入研究时，没有患者出现锥体外系副作用。在6mg /天的剂量下，D-2受体的平均占用率为82%（范围为79%-85%），5-HT2A受体的平均占用率为95%（范围为86%-109%），6例患者出现锥体外系副作用。剂量减少至3mg /d后，D-2受体占用率为72%（范围为53%-78%），5-HT2A受体占用率为83%（范围为65%-112%）。此时有3例患者出现锥体外系副作用。结论：利培酮治疗，6mg /天，可能会导致不必要的高D-2受体占用，随之而来的锥体外系副作用的风险。5-HT2A受体的高占用并不能完全阻止锥体外系的副作用。作者先前建议D-2受体占用的最佳间隔为70%-80%。为了实现这一目标，利培酮，4mg /天，应该是一个合适的抗精神病作用的初始剂量，在大多数患者中，锥体外系副作用的风险最小。
Objective: Multicenter trials with the novel antipsychotic risperidone have suggested a standard dose of 6 mg/day. However, a dose producing the highest response rate in fixed-dose studies is likely to exceed the minimal effective dose in most patients. The aim of this positron emission tomography (PET) study was to suggest a minimal effective dose of risperidone based on measurements of dopamine D-2 and serotonin 5-HT2A receptor occupancy. Method: Eight first-episode or drug-free schizophrenic patients were treated with risperidone, 6 mg/day, for 4 weeks and then 3 mg/day for 2 weeks. PET was performed after 4 and 6 weeks, with [C-11]raclopride to measure Dp receptor occupancy and [C-11]N-methylspiperone to measure 5-HT2A receptor occupancy. Results: Seven patients completed the study and responded to treatment with risperidone. No patient had extrapyramidal side effects at the time of inclusion in the study. At the 6-mg/day dose, mean D-2 receptor occupancy was 82% (range=79%-85%), 5-HT2A receptor occupancy was 95% (range=86%-109%), and six patients had developed extrapyramidal side effects. After dose reduction to 3 mg/day, D-2 receptor occupancy was 72% (range=53%-78%), and 5-HT2A receptor occupancy was 83% (range=65%-112%). Three patients had extrapyramidal side effects at this time. Conclusions: Treatment with risperidone, 6 mg/day, is likely to induce unnecessarily high D-2 receptor occupancy, with a consequent risk of extrapyramidal side effects. High 5-HT2A receptor occupancy did not prevent extrapyramidal side effects completely. The authors previously suggested an optimal interval for D-2 receptor occupancy of 70%-80%. To achieve this, risperidone, 4 mg/day, should be a suitable initial dose for antipsychotic effect with a minimal risk of extrapyramidal side effects in most patients.