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.

精神病和躁动通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。 对于痴呆症伴随着肌肉跨膜（帕金森）运动功能障碍的常见情况，由于治疗行为问题最常使用的药物，神经肌肉抗精神病药可能会恶化帕克森氏症，并且在某些类型的肿块中与严重的外聚体反应有关，因此存在治疗困境。 迄今为止，尚未针对选择用于共存的帕克森主义的原发性痴呆症患者的最有希望的治疗精神病和搅动的替代药物的功效和耐受性，即非典型抗精神病药和胆碱酯酶抑制剂。 此外，在组合使用时，尚无研究检查这两种药物类别的添加效益或风险。 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:喹硫平（QUET；具有良好的锥体室外副作用曲线的非典型抗精神病药），多奈哌齐（胆碱酯酶抑制剂），Quet + donep或安慰剂的组合。 每个受试者都参加了10周的试验，并在基线和分配治疗的6周和10周后进行行为，运动功能，认知，不良事件和其他结果的系统评价。这项研究将提供有关精神病和躁动的最佳治疗的重要信息，这些患者通常遇到原发性痴呆症和帕金森氏症的结合。