沙芬酰胺对帕金森病伴运动波动患者运动和非运动症状的影响。

Effects of Safinamide on Motor and Non-Motor Symptoms in Patients with Parkinson's Disease and Motor Fluctuations.

作者信息

Kulisevsky Jaime, Ferraz Henrique B, Suppa Antonio, Reichmann Heinz

机构信息

Movement Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

Biomedical Research Institute (IIB-Sant Pau), Barcelona, Spain.

出版信息

Eur Neurol. 2024;87(5-6):291-305. doi: 10.1159/000541362. Epub 2024 Sep 27.

INTRODUCTION

Parkinson's disease (PD) involves the progressive loss of dopaminergic neurons, leading to motor and non-motor symptoms that significantly impact patients' quality of life. Safinamide modulates dopaminergic and glutamatergic systems, offering a promising treatment approach.

METHODS

This meta-analysis evaluated the efficacy of safinamide as an add-on therapy to levodopa for PD patients with motor fluctuations. Following PRISMA guidelines, literature searches were conducted in PubMed and Embase (2014-2022). Inclusion criteria were studies on adult PD patients receiving safinamide with levodopa. Outcomes included on-time without troublesome dyskinesia, off-time, UPDRS Part III motor scores, UPDRS Part II activities of daily living scores, PDQ-39 emotional well-being, and GRID-HAMD scores.

RESULTS

Among thirteen eligible studies, safinamide significantly improved on-time without troublesome dyskinesia at 100 mg/day (mean difference [MD]: -0.90; 95% CI: -1.12 to -0.67; p < 0.00001) and 50 mg/day (MD: -0.77; 95% CI: -1.21 to -0.34; p = 0.0005) compared to placebo. It also reduced off-time (100 mg/day: MD: -0.94; 95% CI: -1.19 to -0.70; p < 0.00001; 50 mg/day: MD: -0.72; 95% CI: -1.03 to -0.41; p < 0.00001) and improved UPDRS-III motor scores (100 mg/day: MD: -3.01; 95% CI: -4.15 to -1.86; p < 0.00001; 50 mg/day: MD: -2.93; 95% CI: -5.14 to -0.71; p = 0.001). Mood improvements were noted in PDQ-39 emotional well-being scores (MD: -5.22; 95% CI: -6.90 to -3.54) and GRID-HAMD scores (MD: -0.60; 95% CI: -0.95 to -0.25; p = 0.0009). Safinamide also positively affected pain (RR: 1.10; 95% CI: 1.03 to 1.18).

CONCLUSION

Compared to placebo, safinamide significantly benefits motor and non-motor symptoms in PD patients, but further research is necessary to fully explore its therapeutic potential.

引言

帕金森病（PD）涉及多巴胺能神经元的进行性丧失，导致运动和非运动症状，严重影响患者的生活质量。沙芬酰胺可调节多巴胺能和谷氨酸能系统，提供了一种有前景的治疗方法。

方法

本荟萃分析评估了沙芬酰胺作为左旋多巴附加疗法对有运动波动的PD患者的疗效。按照PRISMA指南，在PubMed和Embase（2014 - 2022年）中进行文献检索。纳入标准为关于接受沙芬酰胺与左旋多巴治疗的成年PD患者的研究。结局指标包括无困扰性异动症的“开”期时间、“关”期时间、统一帕金森病评定量表（UPDRS）第三部分运动评分、UPDRS第二部分日常生活活动评分、帕金森病问卷 - 39（PDQ - 39）情绪健康评分以及汉密尔顿抑郁量表（GRID - HAMD）评分。

结果

在13项符合条件的研究中，与安慰剂相比，沙芬酰胺在每日100毫克（平均差[MD]： - 0.90；95%置信区间[CI]： - 1.12至 - 0.67；p < 0.00001）和每日50毫克（MD： - 0.77；95% CI： - 1.21至 - 0.34；p = 0.0005）时显著改善了无困扰性异动症的“开”期时间。它还减少了“关”期时间（每日100毫克：MD： - 0.94；95% CI： - 1.19至 - 0.70；p < 0.00001；每日50毫克：MD： - 0.72；95% CI： - 1.03至 - 0.41；p < 0.00001）并改善了UPDRS - III运动评分（每日100毫克：MD： - 3.01；95% CI： - 4.15至 - 1.86；p < 0.00001；每日50毫克：MD： - 2.93；95% CI： - 5.14至 - 0.71；p = 0.001）。在PDQ - 39情绪健康评分（MD： - 5.22；95% CI： - 6.90至 - 3.54）和GRID - HAMD评分（MD： - 0.60；95% CI： - 0.95至 - 0.25；p = 0.0009）中观察到情绪改善。沙芬酰胺对疼痛也有积极影响（风险比[RR]：1.10；95% CI：1.03至1.18）。