Berrio Ana, Chrones Lambros, Abler Victor, Hauser Robert A
Acadia Pharmaceuticals Inc., San Diego, CA, USA.
Parkinson's Disease & Movement Disorders Center, University of South Florida, Tampa, FL, USA.
Clin Park Relat Disord. 2025 May 12;12:100342. doi: 10.1016/j.prdoa.2025.100342. eCollection 2025.
Patients with Parkinson's disease almost uniformly experience sleep disorders. Sleep disorders have been linked to the severity of cognitive impairment, which is also a comorbidity with Parkinson's disease psychosis (PDP). Pimavanserin, a highly selective inverse agonist of the serotonin 2A receptor, is approved in the United States for the treatment of hallucinations and delusions in patients with PDP. Other atypical antipsychotics, such as quetiapine and clozapine, are frequently used off-label to treat PDP and have an increased risk of sedation and other sleep-related adverse events (eg, drowsiness, sedation). By contrast, a high degree of specificity for the serotonin 2A receptor may prevent pimavanserin from causing some of the off-target adverse events associated with other atypical antipsychotics. In this review and exploratory analysis, we summarize pimavanserin sleep- and sedation-related safety and tolerability data from past clinical trials, including 6 randomized controlled trials and 2 open-label extensions representing various pimavanserin doses (1 to 51 mg) in healthy volunteers, patients with PDP, and older patients with neurodegenerative disease. The results from our exploratory analyses suggest that pimavanserin may be associated with negligible levels of sedation and other sleep‑related adverse events and may provide improvements in nighttime sleep compared with placebo. Future head-to-head clinical trials will be needed for direct comparisons between pimavanserin and other atypical antipsychotics, such as quetiapine or clozapine.
帕金森病患者几乎都有睡眠障碍。睡眠障碍与认知障碍的严重程度相关，而认知障碍也是帕金森病精神病（PDP）的一种合并症。匹莫范色林是一种高选择性5-羟色胺2A受体反向激动剂，在美国被批准用于治疗PDP患者的幻觉和妄想。其他非典型抗精神病药物，如喹硫平和氯氮平，经常被超适应证用于治疗PDP，且有增加镇静及其他与睡眠相关不良事件（如嗜睡、镇静）的风险。相比之下，对5-羟色胺2A受体的高度特异性可能使匹莫范色林避免引发一些与其他非典型抗精神病药物相关的脱靶不良事件。在本综述和探索性分析中，我们总结了以往临床试验中匹莫范色林与睡眠和镇静相关的安全性及耐受性数据，这些试验包括6项随机对照试验和2项开放标签扩展试验，涉及健康志愿者、PDP患者以及患有神经退行性疾病的老年患者，涵盖了各种匹莫范色林剂量（1至51毫克）。我们探索性分析的结果表明，匹莫范色林可能与可忽略不计的镇静水平及其他与睡眠相关的不良事件相关，并且与安慰剂相比可能改善夜间睡眠。未来需要进行直接比较匹莫范色林与其他非典型抗精神病药物（如喹硫平或氯氮平）的头对头临床试验。
