ACADIA Pharmaceuticals Inc., San Diego, CA, USA.
Department of Neuroscience, University of California, Riverside, Riverside, CA, USA.
J Parkinsons Dis. 2020;10(4):1751-1761. doi: 10.3233/JPD-202058.
Many patients with Parkinson's disease (PD) experience depression.
Evaluate pimavanserin treatment for depression in patients with PD.
Pimavanserin was administered as monotherapy or adjunctive therapy to a selective serotonin reuptake inhibitor or serotonin/noradrenaline reuptake inhibitor in this 8-week, single-arm, open-label phase 2 study (NCT03482882). The primary endpoint was change from baseline to week 8 in Hamilton Depression Scale-17-item version (HAMD-17) score. Safety, including collection of adverse events and the Mini-Mental State Examination (MMSE) and Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III) scores, was assessed in patients who received ≥1 pimavanserin dose.
Efficacy was evaluated in 45 patients (21 monotherapy, 24 adjunctive therapy). Mean (SE) baseline HAMD-17 was 19.2 (3.1). Change from baseline to week 8 (least squares [LS] mean [SE]) in the HAMD-17 was -10.8 (0.63) (95% CI, -12.0 to -9.5; p < 0.0001) with significant improvement seen at week 2 (p < 0.0001) and for both monotherapy (week 8, -11.2 [0.99]) and adjunctive therapy (week 8,-10.2 [0.78]). Most patients (60.0%) had ≥50% improvement at week 8, and 44.4% of patients reached remission (HAMD-17 score ≤7). Twenty-one of 47 patients experienced 42 treatment-emergent adverse events; the most common by system organ class were gastrointestinal (n = 7; 14.9%) and psychiatric (n = 7; 14.9%). No negative effects were observed on MMSE or MDS-UPDRS Part III.
In this 8-week, single-arm, open-label study, pimavanserin as monotherapy or adjunctive therapy was well tolerated and associated with early and sustained improvement of depressive symptoms in patients with PD.
许多帕金森病（PD）患者都经历过抑郁。
评估 pimavanserin 治疗 PD 患者抑郁的效果。
在这项为期 8 周、单臂、开放标签的 2 期研究（NCT03482882）中，pimavanserin 作为单药或辅助治疗，与选择性 5-羟色胺再摄取抑制剂或 5-羟色胺/去甲肾上腺素再摄取抑制剂联合使用。主要终点是从基线到第 8 周汉密尔顿抑郁量表-17 项版本（HAMD-17）评分的变化。在接受至少 1 剂 pimavanserin 的患者中评估了安全性，包括不良事件的发生以及简易精神状态检查（MMSE）和运动障碍协会赞助的帕金森病统一评定量表第三部分修订版（MDS-UPDRS III）评分。
在 45 名患者（21 名单药治疗，24 名辅助治疗）中评估了疗效。基线 HAMD-17 的平均（SE）值为 19.2（3.1）。HAMD-17 从基线到第 8 周的变化（最小二乘[LS]均值[SE]）为-10.8（0.63）（95%CI，-12.0 至-9.5；p<0.0001），第 2 周（p<0.0001）和单药治疗（第 8 周，-11.2[0.99]）和辅助治疗（第 8 周，-10.2[0.78]）都有显著改善。大多数患者（60.0%）在第 8 周时改善≥50%，44.4%的患者达到缓解（HAMD-17 评分≤7）。47 名患者中有 21 名发生 42 例治疗中出现的不良事件；最常见的系统器官类别为胃肠道（n=7；14.9%）和精神科（n=7；14.9%）。在 MMSE 或 MDS-UPDRS 第三部分未观察到任何负面作用。
在这项为期 8 周的单臂、开放标签研究中，pimavanserin 作为单药或辅助治疗具有良好的耐受性，与 PD 患者抑郁症状的早期和持续改善相关。
