Treating Agitation/Psychosis in Dementia/Parkinsonism

治疗痴呆/帕金森症的躁动/精神病

• 批准号: 6609763
• 负责人: ROGER M KURLAN
• 金额: $ 95.81万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-15 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6609763
• 关键词: Alzheimer's disease; Lewy body; Parkinson's disease; antipsychotic agents; anxiety; behavior test; cholinesterase inhibitors; clinical trials; cognition; combination chemotherapy; comorbidity; cooperative study; dementia; drug adverse effect; human middle age (35-64); human old age (65+); human subject; human therapy evaluation; mental disorder chemotherapy; patient oriented research; piperidine; psychological tests; psychopharmacology; psychosis

Psychosis and agitation often occur in the course of dementia and are a major source of patient disability and caregiver stress. For the common situation in which extrapyramidal (parkinsonian) motor dysfunction accompanies dementia, there is a therapeutic dilemma since the most frequently used drugs to treat the behavioral problems, neuroleptic antipsychotics, can worsen parkinsonism and have been associated with severe extrapyramidal reactions in some types of dementia. To date, the efficacy and tolerability of the most promising alternative medications to treat psychosis and agitation, namely atypical antipsychotics and cholinesterase inhibitors, have not been tested in patients with a primary dementia selected for coexisting parkinsonism. Furthermore, no study has examined the possible additive benefits or risks of these 2 drug classes when used in combination. Proposed is a multicenter (20 member sites of the Alzheimer's Disease Cooperative Study [ADCS]), randomized, controlled clinical trial in which 120 subjects with a primary dementia (probable Alzheimer's disease [AD] or probable dementia with Lewy bodies [DLB]) and coexisting parkinsonism will be randomized according to a 2 X 2 factorial design to 1 of 4 treatments: quetiapine (QUET; an atypical antipsychotic with a favorable extrapyramidal side effect profile), donepezil (a cholinesterase inhibitor), the combination of QUET + DONEP, or placebo. Each subject participates in the trial for 10 weeks and systematic ratings of behavior, motor function, cognition, adverse events and other outcomes occur at baseline and after 6 and 10 weeks of assigned treatment. This study will provide important information regarding the optimal treatment of psychosis and agitation for patients with the commonly encountered combination of primary dementia and parkinsonism.

精神病和激越往往发生在痴呆症的过程中，是病人残疾和照顾者压力的主要来源。 对于锥体外系（帕金森）运动功能障碍伴随痴呆的常见情况，存在治疗困境，因为最常用的治疗行为问题的药物（抗精神病药）可使帕金森症恶化，并且在某些类型的痴呆中与严重的锥体外系反应相关。 迄今为止，治疗精神病和激越的最有前途的替代药物，即非典型抗精神病药和胆碱酯酶抑制剂的疗效和耐受性尚未在选择为共存帕金森综合征的原发性痴呆患者中进行测试。 此外，没有研究检查这2种药物联合使用时可能的附加获益或风险。拟定为多中心（阿尔茨海默病合作研究[ADCS]的20个成员站点），随机对照临床试验，其中120名原发性痴呆受试者根据2 × 2析因设计，将可能患有阿尔茨海默病[AD]或可能患有路易体痴呆[DLB]的患者和共存的帕金森综合征随机分配至4种治疗之一：（QUET;具有有利的锥体外系副作用特征的非典型抗精神病药）、多奈哌齐（胆碱酯酶抑制剂）、QUET + DONEP的组合或安慰剂。 每名受试者参加试验10周，并在基线和指定治疗6周和10周后对行为、运动功能、认知、不良事件和其他结局进行系统评级。这项研究将提供重要的信息，最佳治疗的精神病和激越的患者常见的组合原发性痴呆和帕金森氏症。