NEW ATYPICAL NEUROLEPTIC STRATEGIES IN SCHIZOPHRENIA

这项重新提交的报告建议进行一项研究，以测试 瑞昔普利是一种推定的非典型抗精神病药物，对 抗精神病药治疗难治性精神分裂症患者。它还将 支持一项重要的公共和学术联络倡议； 位于巴尔的摩的马里兰大学的治疗抵抗小组。 我们建议，这也将导致制定一项标准 未来测试其他候选非典型药物的临床方案。 这些药物将在药物-药物双盲平行小组中进行测试 设计与氯丙嗪比较，在研究结束时使用氯氮平 描述研究人群的反应水平。病人将会是 因抗精神病药物反应差而被选中，且至少有一次 持续一年的症状，伴随着对至少 三次足够的抗精神病药试验。进入12周的患者 RemxiPride试验也将在六周的时间内没有反应 氟哌啶醇治疗在我们的研究单元。RemoxiPride是一种有效的D2 体内亲和力低的多巴胺受体阻断剂 D2受体，类似于氯氮平。未来的候选药物将是 根据第一届里亚尔的结果被选中，并将成为主题 未来提交的文件。这一设计提供了强大的动力 检验RemoxiPride优越性假说。将对结果进行分析 关于BPRS总分和精神病性症状的改善。 将对阴性症状和副作用变化进行评估。本研究 大小是基于总症状差异11%的预测效果 在阳性症状方面，0.80次方和阿尔法次方相差22% 0.05(双尾)。

This resubmission proposes a study for testing the efficacy of remoxipride a putative atypical antipsychotic drug for efficacy in neuroleptic treatment resistant schizophrenic patients. It will also provide support for a significant public and academic liaison initiative; the Treatment Resistant Unit of the University of Maryland at Baltimore. We propose that it will also lead to the development of a standard clinical protocol to test other candidate atypical drugs in the future. The drugs will be tested in a drug-drug double-blind parallel group design versus chlorpromazine, with clozapine used at the study end to describe the response level of the study population. Patients will be selected for poor neuroleptic response with a history of at least one year of persistent symptoms accompanied by failure to respond to at least three adequate trials of neuroleptics. Patients who enter the 12-week remoxipride trial will also have failed to respond to six weeks of haloperidol therapy on our study unit. Remoxipride is a potent D2 dopamine receptor blocking agent which has a low in vivo affinity for the D2 receptor, similar to clozapine. Future candidate drugs will be selected based on the outcome of the first rial and will be the subject of future submissions. This design provides substantial power for testing the remoxipride superiority hypothesis. Results will be analyzed with regard to improvement in total BPRS score and psychotic symptoms. Negative symptoms and side effect changes will be assessed. This study size is based on a predicted effect of 11% difference in total symptoms and a 22% difference in positive symptoms with a power of 0.80 and alpha of 0.05 (two-tailed).