TREATMENT OF BEHAVIORAL SYMPTOMS IN ALZHEIMERS DISEASE

描述(改编自申请者摘要)：最佳策略 慢性阻塞性肺疾病患者行为并发症的处理 阿尔茨海默病(AD)仍不清楚。来自该小组的先前研究 提示每日剂量超过4毫克的抗精神病药物氟哌啶醇不能 被许多AD门诊患者耐受，每天口服氟哌啶醇2-3毫克 显示出显著优于口服的疗效(61.1%有效率) 氟哌啶醇每日0.5-0.75毫克(有效率31.6%)或安慰剂(有效率26.3%)， 以轻至中度的EPS为主要副作用。 建议的研究分两个阶段进行。在第一阶段，107名AD门诊患者 行为并发症将接受16-20周的开放氟哌啶醇治疗 每日口服1-4毫克，单独滴定至 在疗效和副作用之间实现最佳权衡。应答者 TO第一阶段将参加第二阶段，这是一项为期24周的延续试验 哪些第1阶段的应答者将随机接受继续氟哌啶醇治疗 对照组30例，对照组30例。疗效、副作用和血液的测量 将对级别进行评估。这项研究将解决三个关键问题： 应答的预测因素(第1阶段)、是否需要继续治疗(第1阶段 2)，以及复发和复发时间的预测因素(阶段2)。在 关键的第二阶段继续试验，我们建议测试以下内容 假设：氟哌啶醇的复发率将高于 安慰剂，目标症状持续时间更长，残留更严重 症状学(第一阶段末期)将在第二阶段预测复发。 开放治疗，我们将检验持续时间较长的假设靶点 症状预示不良反应，氟哌啶醇会损害 在运动能力测试中的神经心理表现，但不包括其他 认知领域，血浆氟哌啶醇水平将显示出更强的 与口服剂量相比，口服剂量与结果测量的变化之间存在关联。此外, 关于相对治疗响应性的具体假设将得到检验 以及以行为为主的患者复发的可能性 精神病目标症状。 继续试验将提供重要的临床信息 复发的可能性和一方的持久性之间的权衡 影响(包括长期副作用，如迟发性运动障碍) 患者随机接受氟哌啶醇或安慰剂的持续治疗。总体而言，这 研究将提供新的信息来预测对 行为障碍型AD门诊患者服用抗精神病药物的首批对照研究 关于需要继续服用抗精神病药物的数据，以及新的信息 关于复发的预测因素和复发时间。这些临床数据将是 提高AD患者行为管理的重要性 并发症。

DESCRIPTION (Adapted from applicant's abstract): The optimal strategy for the treatment of behavioral complications in patients with probable Alzheimer's disease (AD) remains unclear. Prior studies from this group indicate that the neuroleptic haloperidol in doses above 4 mg daily cannot be tolerated by many AD outpatients, and that oral haloperidol 2-3 mg daily demonstrates significantly superior efficacy (61.1% response) to either oral haloperidol 0.5-0.75 mg daily (31.6% response) or placebo (26.3% response), with mild to moderate EPS as the main side effect. The proposed study involves two phases. In phase 1, 107 AD outpatients with behavioral complications will receive 16-20 weeks of open haloperidol treatment with an oral dose of 1-4 mg daily, titrated individually to achieve the optimal trade-off between efficacy and side effects. Responders to Phase 1 will participate in Phase 2, a 24-week continuation trial in which Phase 1 responders will be randomized to continuation haloperidol (n=30) or placebo (n=30). Measures of efficacy, side effects, and blood levels will be evaluated. This study will address three key issues: predictors of response (Phase 1), the need for continuation treatment (Phase 2), and predictors of relapse and time to relapse (Phase 2). In the critical Phase 2 continuation trial, we propose to test the following hypotheses: the relapse rate on haloperidol will be greater than that of placebo, longer duration of target symptoms and greater severity of residual symptomatology (end-Phase 1) will predict relapse in Phase 2. In Phase 1 open treatment, we will test the hypotheses that longer duration of target symptoms will predict poor response, haloperidol will impair neuropsychological performance on tests of motor ability but not other cognitive domains, and plasma haloperidol levels will show stronger associations than oral dose with changes in outcome measures. In addition, specific hypotheses will be tested about the relative treatment responsivity and likelihood of relapse in patients with predominantly behavioral versus psychotic target symptoms. The continuation trial will provide important clinical information on the trade-off between the likelihood of relapse and the persistence of side effects (including long-term side effects like tardive dyskinesia) in patients randomized to continuation haloperidol or placebo. Overall, this study will provide new information on the prediction of response to neuroleptics in behaviorally disturbed AD out patients, the first controlled data on the need for continuation neuroleptic treatment, and new information on predictors of relapse and time to relapse. These clinical data will be important in improving the management of AD patients with behavioral complications.