Acute Pharmacotherapy of Late-Life Mania

描述(申请人提供)：患有双相情感障碍(BP)的老年人有严重和衰弱的精神病理，治疗结果差，医疗发病率和死亡率高。缺乏针对晚期BP疾病的对照治疗研究，年轻患者的研究结果可能并不相关，因为与衰老相关的变化可能会降低治疗的耐受性和有效性。在NIMH-DBPA协商一致会议(2001年)上，改善晚年血压紊乱的治疗被确定为优先事项。作为回应，我们提出了首次对患有BP-I躁狂症、混合性躁狂和低躁狂症的老年人进行锂(LI)和异丙戊酸(DV)的随机、双盲、对照比较，旨在测试与老年实践相关的服药条件下副作用和益处的差异。住院和门诊患者(n=306)年龄在60岁及以上，将进行为期9周的研究。参与者将被随机分为LI(0.4-0.99mEq/L；目标0.80-0.99mEq/L)或DV(丙戊酸盐40-99MEq/ml；目标80-99MEg/ml)，并将在前三周以最大耐受浓度接受单一治疗。三周后疗效不满意的患者将接受辅助性奥氮平治疗。耐受性衡量标准将是副作用评级和按目标浓度治疗的比例。疗效措施将是改善情绪症状、功能和生活质量。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。选择的措施与对年轻患者的STEP-BD研究的措施的兼容性将提高这项研究的发现的价值。认识到对BP老年人进行随机研究所固有的困难，我们召集了六个小组(康奈尔大学、贝勒医学院、凯斯西储大学、杜克大学以及宾夕法尼亚大学和匹兹堡大学)，他们拥有老年和年轻成人BP疾病的研究专长，并拥有强大的研究基础设施和临床资源。这些网站有成功合作研究的历史，包括要求苛刻的老年学研究。

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.