TREATMENT OF EARLY ONSET SCHIZOPHRENIA SPECTRUM (TEOSS)

描述（改编自申请人？s摘要）： 目标：这是一个四个相同的修订应用程序之一， 华盛顿大学正在进行的合作R 01提案， 华盛顿州西雅图、北卡罗来纳州大学、北卡罗来纳州查佩尔山、哈佛 马萨诸塞州波士顿医学院和俄亥俄州克利夫兰凯斯西方大学。的 一项研究将检验三种不同抗精神病药物的长期有效性 治疗早发性精神分裂症和精神分裂症的药物 疾病：利培酮（RIS）、奥氮平（奥拉）、吗茚酮（MOL）超过1 年期间。 具体目的：1）确定MOL、RIS和奥拉在降低 精神分裂症和相关疾病青年的精神病性症状; 2） 确定每种药物在一年内维持治疗的能力 3）研究治疗对适应性和神经认知功能的影响 功能;和4）检查这些药物在以下情况下的安全性和耐受性： 儿童人群，特别是对神经锥体的潜在影响 症状和体重增加。 研究设计：168名青少年（年龄8-19岁）精神分裂症， 精神分裂症样障碍或情感障碍和活动性精神病 将在四个地点招募症状。受试者将被随机 分配至三种研究药物之一的双盲治疗。 将遵循标准给药时间表，允许进行修改 取决于受试者的临床状态。抗精神病药物将 在研究的第一周进行交叉递减，以防止 精神病症状症状评级和神经认知测试将 在基线时进行，并在特定时间间隔重复。急性期 治疗将持续8周。具有临床显著改善的受试者 如果没有无法忍受的副作用，将继续维持治疗， 再加44周。将系统评估研究药物的耐受性 通过评估锥体外系副作用和体重增加进行监测。 将修订治疗算法、可靠性测试和数据分析， 四个站点之间的协调。随机化、研究准备 药物和数据库的总体管理将集中在药物管理局。 修订：为了解决审查者的关切，修订后的提案增加了一个 第四个研究中心（哈佛），修订了数据管理和分析计划，以及 调整了一些主要结果指标。 意义：很少有对照研究为临床实践提供信息 用于治疗患有精神障碍的青少年本研究将提供 关于最常用和最有效的方法的比较效力的信息， 青年精神分裂症谱中的代表性抗精神病药物 紊乱

DESCRIPTION (Adapted from the Applicant?s Abstract): Objectives: This is one of four identical revised applications of a collaborative R01 proposal being conducted at the University of Washington, Seattle, WA, University of North Carolina (UNC), Chapel Hill, NC, Harvard Medical School, Boston, MA and Case Western University, Cleveland, Ohio. The study will examine the long-term effectiveness of three different antipsychotic medications in the treatment of early onset schizophrenia and schizoaffective disorder: risperidone (RIS), olanzapine (OLA), the molindone (MOL) over a one year period. Specific Aims: 1) To determine the efficacy of MOL, RIS, and OLA in reducing psychotic symptoms in youth with schizophrenia and related disorders; 2) To determine the ability to sustain treatment over one year with each of these agents; 3) To examine the effects of treatment on adaptive and neurocognitive functioning; and 4) To examine the safety and tolerability of these agents in the pediatric population, particularly potential effects on neuropyramidal symptoms and weight gain. Research Design: 168 youths (ages 8-19 years) with schizophrenia, schizophreniform disorder or schizoaffective disorder and active psychotic symptoms will be recruited across four sites. Subjects will be randomly assigned to double-blind treatment with one of the three study medications. Standard dosage schedules will be followed, with modifications allowed dependent on the clinical status of subjects. Antipsychotic agents will be cross-tapered over the first week of the study to prevent exacerbation of psychotic symptoms. Symptom ratings and neurocognitive testing will be performed at baseline and repeated at specific intervals. The acute phase of treatment will last 8 weeks. Subjects with clinically significant improvement and without intolerable side effects, will continue maintenance therapy for an additional 44 weeks. Tolerance of the study medications will be systematically monitored with assessments for extrapyramidal side effects and weight gain. Revision of treatment algorithms, reliability testing and data analysis will be coordinated between the four sites. Randomization, preparation of study medications, and overall management of the database will be centralized at UNC. Revisions: To address reviewers concerns, the revised proposal has added a fourth site (Harvard), revised the data management and analysis plan, and adjusted some of the primary outcome measures. Significance: There are very few controlled studies to inform clinical practice for the treatment of youth with psychotic disorders. This study will provide information about the comparative effectiveness of the most commonly used and representative antipsychotic drugs in youth with schizophrenia spectrum disorders.