口服金刚烷胺治疗帕金森病异动症和运动波动的疗效与安全性：一项随机对照试验的系统评价和荟萃分析

Efficacy and safety of oral amantadine in Parkinson's disease with dyskinesia and motor fluctuations: a systematic review and meta-analysis of randomised controlled trials.

作者信息

Rujirussawarawong Surachet, Aungsumart Saharat, Kasemsuk Chayut, Limotai Natlada

机构信息

Department of Neurology, Neurological Institute of Thailand, Bangkok, Thailand.

出版信息

BMJ Neurol Open. 2025 Jun 15;7(1):e001115. doi: 10.1136/bmjno-2025-001115. eCollection 2025.

DOI:10.1136/bmjno-2025-001115

PMID:40756069

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12314832/

Abstract

BACKGROUND

Oral amantadine is available in three formulations with distinct pharmacokinetics: immediate-release (IR), delayed-release/extended-release (DR/ER) and immediate-release/extended-release (IR/ER). While all formulations alleviate levodopa-induced dyskinesia, only DR/ER has shown efficacy for motor fluctuations. This meta-analysis evaluates the impact of amantadine formulations on motor complications in Parkinson's disease (PD).

METHODS

A systematic search of PubMed and Scopus (inception to February 2024) identified randomised controlled trials (RCTs) evaluating dyskinesia using various Dyskinesia Rating Scales (DRS) and Unified Parkinson's Disease Rating Scale (UPDRS) or Movement Disorder Society (MDS)-UPDRS part 4 subscores ((MDS-)UPDRS IV), motor fluctuations using 'OFF' time and safety through adverse events. Subgroup analysis assessed formulation-specific effects. The I² statistic determined the use of fixed-effects or random-effects models for efficacy outcomes. Dyskinesia was analysed using standardised mean difference (SMD), motor fluctuations with mean difference (MD) and adverse events with ORs via a fixed-effects Mantel-Haenszel model.

RESULTS

Fourteen RCTs (13 articles) were included. Amantadine significantly reduced dyskinesia (DRS: SMD=-1.32, 95% CI (-1.78 to -0.86); (MDS-)UPDRS IV: SMD=-0.95, 95% CI (-1.33 to -0.58)), with similar effects across formulations. 'OFF' time decreased significantly (MD=-0.66, 95% CI (-0.93 to -0.40)), notably with IR (MD=-0.75, 95% CI (-1.41 to -0.10)) and DR/ER (MD=-0.96, 95% CI (-1.35 to -0.57)), but not IR/ER (MD=-0.23, 95% CI (-0.68 to 0.22)). Adverse events (OR=3.30, 95% CI (2.29 to 4.74)) included dry mouth, hallucinations, peripheral oedema, dizziness and constipation.

CONCLUSIONS

All amantadine formulations alleviated dyskinesia. Additionally, DR/ER improved motor fluctuations, while IR demonstrated benefits, although the evidence is limited by short study durations.

PROSPERO REGISTRATION NUMBER

CRD42024513081.

摘要

背景

口服金刚烷胺有三种具有不同药代动力学的剂型：即释型（IR）、缓释/长效释放型（DR/ER）和即释/长效释放型（IR/ER）。虽然所有剂型都能缓解左旋多巴诱导的异动症，但只有DR/ER对运动波动显示出疗效。本荟萃分析评估了金刚烷胺剂型对帕金森病（PD）运动并发症的影响。

方法

对PubMed和Scopus（创刊至2024年2月）进行系统检索，确定了使用各种异动症评定量表（DRS）和统一帕金森病评定量表（UPDRS）或运动障碍协会（MDS）-UPDRS第4部分子评分（（MDS-）UPDRS IV）评估异动症、使用“关”期评估运动波动以及通过不良事件评估安全性的随机对照试验（RCT）。亚组分析评估了剂型特异性效应。I²统计量确定了对疗效结果使用固定效应或随机效应模型。使用标准化均数差（SMD）分析异动症，使用均数差（MD）分析运动波动，使用固定效应Mantel-Haenszel模型通过比值比（OR）分析不良事件。

结果

纳入了14项RCT（13篇文章）。金刚烷胺显著降低了异动症（DRS：SMD=-1.32，95%CI（-1.78至-0.86）；（MDS-）UPDRS IV：SMD=-0.95，95%CI（-1.33至-0.58）），各剂型效果相似。“关”期显著缩短（MD=-0.66，95%CI（-0.93至-0.40）），尤其是IR（MD=-0.75，95%CI（-1.41至-0.10））和DR/ER（MD=-0.96，95%CI（-1.35至-0.57）），但IR/ER无此效果（MD=-0.23，95%CI（-0.68至0.22））。不良事件（OR=3.30，95%CI（2.29至4.74））包括口干、幻觉、外周水肿、头晕和便秘。