Rissardo Jamir Pitton, Durante Ícaro, Sharon Idan, Fornari Caprara Ana Letícia
Medicine Department, Federal University of Santa Maria, Santa Maria 97105-900, Brazil.
Department of Medicine, Federal University of Fronteira Sul, Passo Fundo 99010-121, Brazil.
Brain Sci. 2022 Sep 23;12(10):1286. doi: 10.3390/brainsci12101286.
Pimavanserin (PMV) is the first approved drug for treating hallucinations and delusions in Parkinson's disease (PD) psychosis. Psychosis is one of the leading causes of nursing home placement in people with PD. Furthermore, hallucinations are a more frequent cause of institutionalization than motor disability or dementia related to PD. The management of PD psychosis involves antipsychotic medications. Most of the drugs in this class directly block dopamine D2 receptors, leading to significantly worsening motor symptoms in patients with PD. The most commonly used medications for managing PD psychosis are quetiapine, clozapine, and PMV. This literature review aims to study pimavanserin's history, mechanism, clinical trials, and post-marketing experience. PMV is a potent 5-HT2A receptor antagonist/inverse agonist. Moreover, this drug can interact with 5-HT2C receptors. We calculated some physicochemical descriptors and pharmacokinetic properties of PMV. Eight clinical trials of PMV and PD psychosis are registered on ClinicalTrials.gov. Only four of them have complete results already published. Meta-analytic results showed that PMV efficacy is inferior to clozapine. However, PMV has a significantly lower number of side-effects for managing psychosis in PD. Medicare database assessment revealed 35% lower mortality with PMV compared to other atypical antipsychotics. Moreover, sensitive statistical analysis demonstrated that PMV is a protective factor for the risk of falls in individuals with PD.
匹莫范色林（PMV）是首个被批准用于治疗帕金森病（PD）精神病性症状的幻觉和妄想的药物。精神病是导致PD患者入住疗养院的主要原因之一。此外，幻觉比PD相关的运动功能障碍或痴呆更常导致患者被收容机构收留。PD精神病的治疗涉及使用抗精神病药物。这类药物中的大多数直接阻断多巴胺D2受体，导致PD患者的运动症状显著恶化。治疗PD精神病最常用的药物是喹硫平、氯氮平和PMV。这篇文献综述旨在研究匹莫范色林的历史、作用机制、临床试验和上市后经验。PMV是一种强效的5-羟色胺2A受体拮抗剂/反向激动剂。此外，该药物还可与5-羟色胺2C受体相互作用。我们计算了PMV的一些物理化学描述符和药代动力学性质。在ClinicalTrials.gov上注册了八项关于PMV与PD精神病的临床试验。其中只有四项已经发表了完整的结果。荟萃分析结果显示，PMV的疗效不如氯氮平。然而，在治疗PD精神病方面，PMV的副作用明显较少。医疗保险数据库评估显示，与其他非典型抗精神病药物相比，使用PMV的患者死亡率降低了35%。此外，敏感性统计分析表明，PMV是PD患者跌倒风险的一个保护因素。
