NEW ATYPICAL NEUROLEPTIC STRATEGIES IN SCHIZOPHRENIA

本重新提交的文件建议进行一项研究， 瑞莫西必利是一种公认的非典型抗精神病药物， 抗精神病药治疗的精神分裂症患者。 它还将 为重要的公众和学术联络倡议提供支持; 位于巴尔的摩的马里兰州大学的耐药单位。 我们建议，这也将导致一个标准的发展 临床方案，以测试其他候选的非典型药物在未来。 这些药物将在药物-药物双盲平行组中进行测试 设计与氯丙嗪相比，在研究结束时使用氯氮平， 描述研究人群的反应水平。 患者将 选择精神抑制剂反应差的患者，至少有一次 一年的持续症状伴随着未能响应至少 三次足够的精神抑制剂试验 进入第12周的患者 Remoxipride试验也未能对六周的 氟哌啶醇治疗的病人 Remoxipride是一种有效的D2 多巴胺受体阻断剂，其对多巴胺受体具有低的体内亲和力， D2受体，类似于氯氮平。 未来的候选药物将是 根据第一个rial的结果选择，并将作为受试者 未来的提交。 该设计为以下设备提供了强大的动力： 测试瑞莫西必利的优越性假设。 将分析结果 BPRS总分和精神病性症状的改善。 将评估阴性症状和副作用变化。 本研究 大小基于总症状差异11%的预测效应 阳性症状的差异为22%，功效为0.80和α 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).