Treating Agitation/Psychosis in Dementia/Parkinsonism

精神病和躁动通常发生在痴呆症的过程中，是患者残疾和照顾者压力的主要来源。对于锥体外系(帕金森病)运动功能障碍伴随痴呆的常见情况，存在治疗两难境地，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，并与某些类型痴呆的严重锥体外系反应有关。到目前为止，最有希望治疗精神病和躁动的替代药物，即非典型抗精神病药物和胆碱酯酶抑制剂的有效性和耐受性尚未在被选为并存帕金森氏症的原发性痴呆患者中进行测试。此外，还没有研究检查这两类药物联合使用时可能产生的附加益处或风险。建议的是一项多中心(阿尔茨海默病合作研究[ADCS]的20个成员站点)的随机对照临床试验，其中120名患有原发性痴呆(可能是阿尔茨海默病[AD]或可能有路易体痴呆[DLB])的患者将根据2×2析因设计被随机分配到4种治疗方法中的一种：奎硫平(QUET；一种具有良好锥体外系副作用的非典型抗精神病药物)、多奈哌齐(一种胆碱酯酶抑制剂)、QUET的组合DONEP或安慰剂。每个受试者参加为期10周的试验，在基线和分配的治疗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级。这项研究将为患有常见的原发性痴呆和帕金森综合症的患者提供有关精神病和激越的最佳治疗的重要信息。

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.