Acute Pharmacotherapy of Late-Life Mania

描述（由申请人提供）：患有双相情感障碍（BP）的老年人具有严重和使人衰弱的精神病理学，治疗结果差，以及高医学发病率和死亡率。老年BP障碍的对照治疗研究缺乏，年轻患者的发现可能不相关，因为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年）上，改善晚期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）和双丙戊酸钠（DV）在老年人与BP-I躁狂，混合和轻躁狂发作，旨在测试的差异，副作用和效益的剂量条件下，老年实践。将对年龄≥ 60岁的住院和非住院患者（n=306）进行为期9周的研究。受试者将被随机分配至LI（0.4-0.99 mEq/L;目标0.80-0.99 mEq/L）或DV（丙戊酸盐40-99 mcg/ml;目标80-99 mcg/ml）组，并将在前3周内接受最大耐受浓度的单药治疗。三周后疗效不满意的患者将接受奥氮平治疗。耐受性指标将是副作用评级和目标浓度下接受治疗的比例。疗效指标将是情绪症状以及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局的选定因素进行二次分析。选定的措施与年轻患者的STEP-BD研究的措施的兼容性将提高本研究结果的价值。认识到BP老年人随机研究中固有的困难，我们汇集了六个小组（康奈尔大学，贝勒医学院，凯斯西储，杜克，宾夕法尼亚大学和匹兹堡大学），在晚年和年轻成人BP疾病的研究专业知识，并具有强大的研究基础设施和临床资源。这些地点有着成功的合作研究历史，包括要求苛刻的老年医学研究。

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.