STN/Three Individual Projects: COATS, METS, CRSTN

COATS：精神分裂症最佳抗精神病药物治疗的比较 摘要： 本研究采用创新的、先发制人的方法预防和管理不良反应，比较阿立哌唑、奋乃静和奥氮平治疗早期精神分裂症或情感性精神障碍患者以及近期病情加重患者的疗效。目标是通过最大限度地减少不良反应，通过预先管理这些药物的已知不良反应来优化临床结果。60例首次因精神分裂症住院5年内的患者将随机接受长达6个月的奥氮平、奋乃静或阿立哌唑开放标签治疗。精神病理学评分将在不知情的情况下进行。 将使用预先确定的一致策略监测和管理体重增加、胰岛素抵抗、胆固醇升高和锥体外系副作用（EPSE）。 无法通过预先确定的策略减轻的这些不良结局的不可管理和令人不安的水平将被视为结局失败。 由于这是一项试点研究，具体目标反映了为更大规模的确定性研究确定可行性的努力。 METS：二甲双胍治疗精神分裂症中抗精神病药物诱导的体重增加 摘要： 精神分裂症患者的预期寿命比一般人群短25年。与发病率和死亡率相关的体重增加和代谢异常在精神分裂症中很常见，并与几种抗精神病药物有关。然而，改善体重增加和代谢异常风险的最适当策略尚未建立。一种创新的方法，二甲双胍连续治疗，在精神病早期患者的随机研究中显示出有希望的结果，但这种方法尚未在慢性精神分裂症或情感障碍患者中进行大规模的系统性测试。这项研究将招募140名患有精神分裂症或情感性精神障碍的个体，他们的BMI为27，并接受一种或两种抗精神病药物的联合治疗。 受试者将随机接受二甲双胍或安慰剂的强化治疗。所有参与者都将接受旨在降低心血管疾病风险的手动行为干预。 这项研究开始时是一项试点研究，但由于它是如此的可行和重要，它被扩大到包括一个更大的样本量的全面疗效研究。 因此，具体目标既包括可行性成果（目标1-3），也包括实质性成果目标（目标4-5）。 CRYSTAL：精神分裂症试验网络上的认知补救 摘要： 本研究将确定在不专门从事这一研究领域的网站网络中实施认知补救计划的可行性，并将有助于确定多站点认知补救项目本身作为干预措施和作为药理学认知增强试验平台的可行性。将48例精神分裂症或情感性精神障碍患者随机分配至为期8 - 12周的认知矫正计划或由视频游戏组成的对照计划。由于这是一项试点研究，具体目标反映了为更大规模的确定性研究确定可行性的努力。

COATS: Comparison of Optimal Antipsychotic Treatments for Schizophrenia Abstract: Using innovative, preemptive approaches to prevent and manage adverse effects, this study compares aripiprazole, perphenazine, and olanzapine in the treatment of patients who are in the early years of schizophrenia or schizoaffective disorder and who have had a recent exacerbation of their illness. The goal is to optimize clinical outcomes by minimizing adverse effects, by preemptively managing known adverse reactions to these medications. Sixty patients who are within 5 years of their first hospitalization for schizophrenia will be randomized to up to 6 months of open-label treatment with olanzapine, perphenazine, or aripiprazole. Psychopathology ratings will be done blind to treatment assignment. There will be monitoring for and management of weight gain, insulin resistance, cholesterol elevation, and extrapyramidal side effects (EPSE) using pre-determined and consistent strategies. Unmanageable and troubling levels of these adverse outcomes that cannot be attenuated by the pre-determined strategies will be considered outcome failures. Because this is a pilot study, the specific aims reflect efforts to establish feasibility for a larger, definitive study. METS: Metformin in the Treatment of Antipsychotic-Induced Weight Gain in Schizophrenia Abstract: Life expectancy for individuals with schizophrenia is up to 25 years shorter than for the general population. Weight gain and metabolic abnormalities that are associated with morbidity and mortality are common in schizophrenia and have been linked with several antipsychotic medications. However, the most appropriate strategies to ameliorate the risks of weight gain and metabolic abnormalities have not been established. One innovative approach, adjunctive treatment with metformin, has shown promising results in randomized studies of patients early in the course of psychotic illnesses, but this approach has not been systematically tested on a large scale among individuals with chronic schizophrenia or schizoaffective disorder. This study will enroll 140 individuals with schizophrenia or schizoaffective disorder who have a BMI ≥ 27 and are treated with one or a combination of two antipsychotic medications. Participants will be randomized to augmentation treatment with metformin or placebo. All participants will receive a manualized behavioral intervention aimed at reducing their risk of cardiovascular disease. The study began as a pilot study, but because it was so feasible and important, it was expanded to include a larger sample size for a full efficacy study. Thus the specific aims include both feasibility outcomes (Aims 1-3) as well as substantive outcome goals (Aims 4-5). CRSTN: Cognitive Remediation on the Schizophrenia Trials Network Abstract: This study will determine the feasibility of implementing a cognitive remediation program in a network of sites that do not specialize in this area of research, and will help determine the feasibility of multi-site cognitive remediation projects as an intervention in itself and as a platform for pharmacologic cognitive enhancement trials. Forty eight (48) patients with schizophrenia or schizoaffective disorder will be randomly assigned to 8 - 12 weeks of a cognitive remediation program or a control program consisting of video games. Because this is a pilot study, the specific aims reflect efforts to establish feasibility for a larger, definitive study.