TREATMENT OF BEHAVIORAL SYMPTOMS IN ALZHEIMERS DISEASE

描述（改编自申请人摘要）： 可能患有行为并发症的患者的治疗 阿尔茨海默病（AD）仍不清楚。 该小组之前的研究 表明精神抑制剂氟哌啶醇在剂量超过4毫克，每天不能 许多AD门诊患者耐受，口服氟哌啶醇2-3 mg/d 显示出显著优于口服或口服的上级疗效（61.1%的应答） 氟哌啶醇0.5-0.75 mg/天（31.6%应答）或安慰剂（26.3%应答）， 以轻中度EPS为主。 拟议的研究包括两个阶段。 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1-4 mg口服剂量治疗，单独滴定， 在功效和副作用之间实现最佳平衡。 应答者 将参加第2阶段，这是一项为期24周的持续试验， 哪些I期应答者将随机接受氟哌啶醇持续治疗 （n=30）或安慰剂（n=30）。 疗效、副作用和血液指标 水平将得到评估。 这项研究将涉及三个关键问题： 反应的预测因素（1期）、继续治疗的需要（2期） 2），以及复发和复发时间的预测因素（第2阶段）。 在 关键的2期延续试验，我们建议测试以下内容 假设：氟哌啶醇的复发率将大于 安慰剂、目标症状持续时间更长和残留严重程度更高 肿瘤学（1期结束）将预测2期的复发。 在阶段1中 开放治疗，我们将测试的假设，更长的持续时间的目标 症状将预示不良反应，氟哌啶醇将损害 在运动能力测试中的神经心理学表现，而不是其他 认知领域，血浆氟哌啶醇水平将显示更强的 与口服剂量相比，口服剂量与结果指标变化之间的相关性。 此外，本发明还提供了一种方法， 将检验关于相对治疗反应性的特定假设 和复发的可能性， 精神病目标症状 继续试验将提供关于以下方面的重要临床信息： 复发的可能性和持续性之间的权衡 影响（包括迟发性运动障碍等长期副作用） 随机分配至持续氟哌啶醇或安慰剂组的患者。 总的来说，这 研究将提供新的信息，预测对 精神抑制剂在行为障碍AD门诊患者，第一个控制 关于需要继续精神抑制剂治疗的数据和新信息 复发的预测因素和复发时间。 这些临床数据将 在改善AD患者的行为管理方面具有重要意义 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.