Treating Agitation/Psychosis in Dementia/Parkinsonism

治疗痴呆/帕金森症的躁动/精神病

• 批准号: 6776918
• 负责人: ROGER M KURLAN
• 金额: $ 81.84万
• 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 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6776918
• 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.

精神病和躁动经常发生在痴呆症过程中，是患者残疾和护理人员压力的主要来源。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，抗精神病药物，可加重帕金森病，并与某些类型的痴呆严重的锥体外系反应有关。迄今为止，治疗精神病和躁动的最有希望的替代药物，即非典型抗精神病药和胆碱酯酶抑制剂的疗效和耐受性，尚未在患有共存帕金森病的原发性痴呆患者中进行测试。此外，还没有研究检验这两类药物联合使用时可能产生的附加益处或风险。拟议的是一项多中心（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（可能的阿尔茨海默病[AD]或可能的痴呆伴路易体[DLB]）和共存的帕金森患者将根据2 × 2因子设计随机分为4种治疗中的1种：喹硫平(QUET；一种具有良好锥体外系副作用的非典型抗精神病药)，多奈哌齐（一种胆碱酯酶抑制剂），QUET + DONEP联合用药，或安慰剂。每位受试者参与试验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、不良事件和其他结果进行系统评分。本研究将为原发性痴呆和帕金森病合并患者的精神病和躁动的最佳治疗提供重要信息。