Acute Pharmacotherapy of Late-Life Mania

描述（由申请人提供）：老年双相情感障碍（BP）具有严重和衰弱的精神病理，治疗效果差，医疗发病率和死亡率高。目前缺乏对老年BP疾病的对照治疗研究，年轻患者的研究结果可能不相关，因为与年龄相关的变化可能会降低治疗的耐受性和疗效。在NIMH-DBPA共识会议（2001）上，改善晚年BP疾病的治疗被确定为优先事项。作为回应，我们提出了第一个随机、双盲、对照比较锂（LI）和双丙戊酸（DV）在BP-I躁狂、混合型和轻躁发作的老年人中的应用，旨在测试与老年实践相关的剂量条件下副作用和益处的差异。对60岁及以上住院和门诊患者（306例）进行为期9周的研究。受试者将随机分为LI组（0.4-0.99 mEq/L，靶点0.80-0.99 mEq/L）或DV组（丙戊酸40-99 meg/ml，靶点80-99 meg/ml），并在前三周以最大耐受浓度进行单药治疗。三周后反应不满意的患者将辅助服用奥氮平。耐受性措施将是副作用评级和按目标浓度处理的比例。疗效指标将是情绪症状、功能和生活质量的改善。为检验主要假设而获得的数据将允许对可能改变结果的选定因素进行二次分析。选择的测量方法与年轻患者的STEP-BD研究方法的兼容性将提高本研究结果的价值。认识到随机研究高血压老年人所固有的困难，我们汇集了六个研究小组（康奈尔大学、贝勒医学院、凯斯西储大学、杜克大学、宾夕法尼亚大学和匹兹堡大学），他们具有晚年和年轻人血压疾病的研究专长，并拥有强大的研究基础设施和临床资源。这两个网站有成功合作研究的历史，包括要求很高的老年研究。

DESCRIPTION (provided by applicant): Elders with bipolar disorders (BP) have severe and debilitating psychopathology, poor treatment outcomes, and high medical morbidity and mortality. Controlled treatment studies for late-life BP disorder are lacking, and findings in young patients may not be relevant because aging-related changes may reduce the tolerability and efficacy of treatments. Improving the treatment of late-life BP disorder was identified as a priority at the NIMH-DBPA Consensus Conference (2001). In response, we propose the first randomized, double-blind, controlled comparison of lithium (LI) and divalproex (DV) in elders with BP-I manic, mixed and hypomanic episodes, designed to test differences in side effects and benefits under dosing conditions relevant to geriatric practice. Hospitalized and ambulatory patients (n=306) aged 60 years and older will be studied for 9 weeks. Participants will be randomized to LI (0.4-0.99 mEq/L; target 0.80-0.99 mEq/L) or DV (valproate 40-99 meg/ml; target 80-99 meg/ml), and will be treated with monotherapy in the first three weeks at maximum tolerated concentrations. Patients with unsatisfactory response after three weeks will receive adjunctive olanzapine. The tolerability measures will be side effect ratings and the proportion treated at target concentrations. The efficacy measures will be improvement in mood symptoms and in function and quality of life. Data obtained for testing the primary hypotheses will allow secondary analyses of selected factors which may modify outcomes. Compatibility of selected measures with those of the STEP-BD study of younger patients will enhance the value of findings from this study. Recognizing the difficulties inherent in a randomized study of BP elders, we brought together six groups (Cornell, Baylor College of Medicine, Case Western Reserve, Duke, and Universities of Pennsylvania and Pittsburgh) with research expertise in late-life and young adult BP disorders, and with strong research infrastructure and clinical resources. The sites have a history of successful collaborative research, including demanding geriatric studies.