Donepezil for the treatment of psychosis in dementia with Lewy bodies
Donepezil for the treatment of psychosis in dementia with Lewy bodies
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多奈哌齐治疗路易体痴呆症精神病
DOI：
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发表时间：
2000
影响因子：
4
通讯作者：
R. Howard
中科院分区：
文献类型：
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作者：
E. Fergusson;R. Howard
多奈哌齐目前在英国获得许可，仅用于阿尔茨海默病中轻度至中度痴呆的对症治疗。在与皮质路易体 (DLB) 相关的痴呆病例中，胆碱乙酰转移酶的水平可能特别低 (Perry 等人，1990)，突触前胆碱能投射神经元的严重耗竭与 DLB 颞皮层 m1 受体的上调有关 (Shiozaki 等人，1999)。尚未发表过使用多奈哌齐治疗 DLB 的试验，但个别病例报告表明其有效（Shea 等人，1998 年；Geizer 和 Ancill，1998 年）。我们报告了两例 DLB 病例，其中多奈哌齐治疗使行为、认知和精神症状显着改善。一名 77 岁的寡妇从一所住宅院被送往医院，她在那里变得越来越困惑，并且间歇性地对工作人员和居民具有攻击性。她拒绝吃喝，因为她认为食物有毒，并将自己锁在房间里，导致警察被工作人员叫到家里。入院时，她的行为在极度痛苦和攻击性之间摇摆，而在她平静并能够与工作人员互动的时期之间。当她变得咄咄逼人时，她相信自己正在被轰炸，正在失去孩子，并且正在中毒。即使在平静的情况下，她仍然感到困惑并出现精神病症状。她在 MMSE（Folstein et al., 1975）上的最好成绩是 5/30。每天服用最多 10 毫克奥氮平治疗 18 天，并在严重躁动时（当她的行为被认为使她面临身体危险时额外肌注劳拉西泮）并没有改变她的行为或症状。服用 10 毫克多奈哌齐 14 天后，她没有出现精神病症状，也没有出现痛苦的情况，她的自我保健能力得到改善，饮食和睡眠都很好。停用奥氮平，四个星期后，她仍然没有精神病症状，她的 MMSE 评分为 14/30。在初步评估后，建议她接受专业护理人员的持续护理，目前正在考虑将她安置在疗养院。一名 74 岁的退休工程师有 18 个月认知功能恶化和情绪波动的病史，根据《心理健康法》第 2 条入院。这是在两个月的精神病症状波动之后发生的。他曾看到面孔扭曲的掘墓人从他卧室的地板上升起，并感觉到他们在触碰他。他还曾在半夜前往警察局，认为自己被绑架了。入院时，他已完全适应并在 MMSE 上取得了 29/30 的成绩。然而，他的演讲杂乱无章，难以解释和理解复杂的想法。心理评估显示执行功能受损，最明显的是非语言测试，以及视觉空间功能明显受损。在入院的第一周，他有两次出现幻视，变得非常烦躁，并且破坏病房的家具。开始服用 10 毫克多奈哌齐，治疗一周后，他变得更加平静，讲话也不再那么含糊其辞。经过三周的治疗后，他不再出现躁动或精神病症状，目前正在制定计划让他回家与女儿住在一起。在这两个可能的 DLB 病例中，多奈哌齐治疗与行为和认知功能的改善以及精神病症状的消失之间存在明显的时间关系。两名患者在治疗前或治疗期间都没有帕金森病症状，因此无法从此类开放案例研究中得出确切的结论。鉴于用精神安定药治疗 DLB 精神病症状的潜在危险（McKeith 等，1992），胆碱酯酶抑制剂
Donepezil is currently licensed in the UK for the symptomatic treatment of mild to moderate dementia in Alzheimer's disease only. Levels of choline acetyltransferase may be particularly low in cases of dementia associated with cortical Lewy bodies (DLB) (Perry et al., 1990) and a severe depletion of presynaptic cholinergic projective neurons is associated with an upregulation of m1 receptors in the temporal cortex in DLB (Shiozaki et al., 1999). There have been no published trials of the use of donepezil in DLB, but individual case reports suggest ecacy (Shea et al., 1998; Geizer and Ancill, 1998). We report two DLB cases in which donepezil treatment resulted in signi®cant improvement in behaviour, cognition and psychotic symptoms. A 77-year-old widow was admitted to hospital from a residential home where she had been increasingly confused and intermittently aggressive to sta and residents. She was refusing to eat or drink because she believed the food was poisoned and had barricaded herself in her room, resulting in the police being called to the home by sta. On admission, her behaviour ̄uctuated between acute distress and aggression and periods when she was calm and able to interact with sta. When aggressive, she believed she was being bombed, was losing her children and being poisoned. Even when calm, she continued to be confused and to experience psychotic symptoms. Her best score on the MMSE (Folstein et al., 1975) was 5/30. Eighteen days of olanzapine treatment at up to 10 mg per day with additional intramuscular lorazepam at times of severe agitation when her behaviour was thought to put her at physical risk, did not change her behaviour or symptoms. After 14 days of donepezil 10 mg she had no psychotic symptoms, no episodes when she was distressed, her self care improved and she was eating and sleeping well. Olanzapine was stopped and after a further four weeks she remained free from psychotic symptoms and her MMSE score was 14/30. Having been recommended for continuing care with specialist nursing following her initial assessment, she is now being considered for placement within a nursing home. A 74-year-old retired engineer with an 18 month history of deteriorating cognitive function and ̄uctuating mood, was admitted to hospital under Section 2 of the Mental Health Act. This followed two months of ̄uctuating psychotic symptoms. He had seen grave diggers with distorted faces rising up through his bedroom ̄oor and felt them touch him. He had also gone to the police station in the middle of the night believing he had been kidnapped. On admission, he was fully orientated and scored 29/30 on the MMSE. His speech was rambling however, and he had diculty explaining and understanding complex ideas. Psychological assessment showed impairment in executive functioning, most marked on non-verbal tests, and marked impairment in visuospatial functions. During the ®rst week of admission there were two episodes in which he experienced visual hallucinations and became very agitated and destructive of ward furnishings. Donepezil 10 mg was started and after one week of treatment he was calmer and his speech was much less circumstantial. After three weeks of treatment there had been no further episodes of agitation or psychotic symptoms and plans are being made for him to return home to live with his daughter. In both these cases of probable DLB, there was a clear temporal relationship between treatment with donepezil and improvement in behaviour and cognitive function and disappearance of psychotic symptoms. Neither patient had parkinsonian symptoms before or during treatment and ®rm conclusions cannot be drawn from such open case studies. Given the potential dangers of treating psychotic symptoms in DLB with neuroleptics (McKeith et al., 1992), cholinesterase inhibitors