Gardner Family Center for Parkinson's Disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, Ohio, USA.
ACADIA Pharmaceuticals Inc., San Diego, California, USA.
Mov Disord. 2018 Nov;33(11):1769-1776. doi: 10.1002/mds.27488. Epub 2018 Nov 2.
PD psychosis is often associated with cognitive impairment, including dementia, and involves dopaminergic, serotonergic, and cholinergic mechanisms.
To evaluate the differential effect of the antipsychotic pimavanserin, a selective serotonin 2A receptor inverse agonist, in PD psychosis patients with versus without cognitive impairment and in those receiving versus not receiving cognitive-enhancing medications.
Data from the pivotal randomized clinical trial of pimavanserin for PD psychosis were stratified by (1) screening MMSE score as cognitively impaired (21-24) versus unimpaired (≥25) and (2) concomitant use versus nonuse of cognitive-enhancing medications. The primary outcome measure was change in the PD-adapted Scale for the Assessment of Positive Symptoms.
Mean (pimavanserin vs. placebo) change from baseline was larger in the cognitively impaired (n = 50; -6.62 vs. -0.91; P = 0.002) versus the cognitively unimpaired (n = 135; -5.50 vs. -3.23; p = 0.046) group. The comparable change was -6.04 versus -2.18 (P = 0.012) and -5.66 versus -3.15 (P = 0.041) in patients treated (n = 69) and not treated (n = 116) with concomitant cognitive-enhancing medication. Pimavanserin was similarly tolerated across all cognitive groups with no additional safety concerns identified. Overall adverse event rates were comparable across the concomitant cognitive-enhancing medication groups; however, rates of serious adverse events and discontinuations attributed to adverse events were increased in patients taking cholinesterase inhibitors.
The antipsychotic effect of pimavanserin is robust in PD patients with cognitive impairment and may be enhanced by concomitant cognitive-enhancing medication use. Future prospective studies are needed to confirm these preliminary findings. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
PD 精神病常伴有认知障碍，包括痴呆，并涉及多巴胺能、5-羟色胺能和胆碱能机制。
评估抗精神病药 pimavanserin（一种选择性 5-羟色胺 2A 受体反向激动剂）对 PD 精神病伴或不伴认知障碍患者以及同时使用或不使用认知增强药物患者的差异作用。
根据（1）筛查 MMSE 评分（认知受损[21-24]与未受损[≥25]）和（2）同时使用或不使用认知增强药物，对 pimavanserin 治疗 PD 精神病的关键性随机临床试验数据进行分层。主要结局测量指标为 PD 适应的阳性症状评定量表的变化。
与认知未受损（n = 135；-3.23；p = 0.046）相比，认知受损（n = 50；-6.62；P = 0.002）患者的基线变化平均值（pimavanserin 与安慰剂）更大。接受（n = 69）和未接受（n = 116）同时认知增强药物治疗的患者，其类似的变化分别为-6.04 与-2.18（P = 0.012）和-5.66 与-3.15（P = 0.041）。在所有认知组中，pimavanserin 的耐受性相似，未发现其他安全性问题。总体不良事件发生率在伴有认知增强药物的各组之间相似；然而，接受胆碱酯酶抑制剂的患者严重不良事件和因不良事件而停药的发生率增加。
pimavanserin 对伴有认知障碍的 PD 患者具有强大的抗精神病作用，并且可能通过同时使用认知增强药物而增强。需要进一步开展前瞻性研究来证实这些初步发现。
