帕金森病运动障碍患者中停用金刚烷胺：AMANDYSK 试验。

Withdrawing amantadine in dyskinetic patients with Parkinson disease: the AMANDYSK trial.

机构信息

From INSERM, Clinical Investigation Center 9302 (F.O.-M., C.B.-C., E.D., M.G., C.T., A.S., O.R.), and Department of Neurology (F.O.-M., C.B.-C., O.R.), University Hospital of Toulouse; INSERM, Clinical Investigation Center 9503 (J.-C.C., A.-M.B., M.V.), and AP-HP, Department of Neurology (J.-C.C., A.-M.B., M.V.), Pitié-Salpêtrière Hospital, Paris; CRICM UPMC/INSERM UMR_S975 CNRS UMR7225 (J.-C.C., M.V.), Institut de la Moelle et du Cerveau, Université Pierre Marie Curie Paris-6, Salpêtrière, Paris; AP-HM (J.-P.A.), Department of Neurology, Timone Hospital, Marseille; Department of Clinical Pharmacology (C.B.-C., C.T., A.S., O.R.), University of Medicine, Toulouse; INSERM (C.B.-C., O.R.), and Université de Toulouse, UPS (C.B.-C., O.R.), Imagerie cérébrale et handicaps neurologiques, UMR 825, Toulouse; Department of Neurology (P.D., T.L.), University Hospital of Nantes; Department of Neurology (A.D.), University Hospital of Lille; Department of Neurology (F.D.), University Hospital of Clermont-Ferrand; Department of Neurology (W.M., F.T.), University Hospital of Bordeaux; and Department of Neurology (F.V.), Pays-d'Aix Hospital, Aix-en-Provence, France.

出版信息

Neurology. 2014 Jan 28;82(4):300-7. doi: 10.1212/WNL.0000000000000050. Epub 2013 Dec 26.

DOI:10.1212/WNL.0000000000000050

PMID:24371304

Abstract

OBJECTIVE

The AMANDYSK trial was designed to assess long-term efficacy of chronic treatment with amantadine in patients with Parkinson disease (PD) and levodopa-induced dyskinesia (LID).

METHODS

This was a 3-month, multicenter, randomized, double-blind, placebo-controlled, parallel-group, wash-out study conducted in 57 amantadine-treated (≥200 mg/d for ≥6 months) dyskinetic patients with PD. The primary outcome measure was the change from baseline in a Unified Parkinson's Disease Rating Scale (UPDRS) dyskinesia subscore (items 32 [duration] + 33 [severity]). Secondary outcomes included other LID measurements ("responders" analysis, premature dropout for LID, Abnormal Involuntary Movement Scale). Exploratory outcomes included time with troublesome dyskinesia as measured by diaries, UPDRS Motor Examination (part III) for motor symptoms of PD, and fatigue and apathy scores for nonmotor symptoms.

RESULTS

UPDRS items 32 + 33 deteriorated more in patients switched to placebo ("discontinuing" group) (+1.7 ± 2.0 units; 95% confidence interval 0.9, 2.4) as compared with those maintained on amantadine ("continuing" group) (+0.2 ± 1.5 units; 95% confidence interval -0.4, 0.8; p = 0.003). Secondary outcomes confirmed this difference because there were significantly more responders, more dropouts for LID, greater increase in "ON" time with troublesome dyskinesia, and greater worsening of Abnormal Involuntary Movement Scale score in the discontinuing group. There were no between-group differences in the UPDRS Motor Examination, whereas apathy (as measured by caregivers) and fatigue scores tended to worsen more in patients randomized to placebo.

CONCLUSION

Wash-out of amantadine in dyskinetic patients with PD significantly worsened LID. No significant effect was observed on motor parkinsonian symptoms, while exploratory outcomes suggested that amantadine might improve apathy and fatigue in such patients.

CLASSIFICATION OF EVIDENCE

This article provides Class II evidence that in patients with PD, withdrawing amantadine significantly aggravates LID in a median time of 7 days.

摘要

目的

AMANDYSK 试验旨在评估金刚烷胺在帕金森病（PD）伴左旋多巴诱导的运动障碍（LID）患者中的长期疗效。

方法

这是一项为期 3 个月、多中心、随机、双盲、安慰剂对照、平行组、洗脱研究，在 57 名接受金刚烷胺治疗（≥200mg/d，≥6 个月）的伴运动障碍的 PD 患者中进行。主要观察指标是统一帕金森病评定量表（UPDRS）运动障碍评分（项目 32[持续时间]+33[严重程度]）的基线变化。次要观察指标包括其他 LID 测量（“应答者”分析、LID 过早停药、不自主运动量表）。探索性观察指标包括日记中记录的麻烦性运动障碍时间、PD 的 UPDRS 运动检查（第三部分）和非运动症状的疲劳和淡漠评分。

结果

切换到安慰剂的患者（“停药”组）的 UPDRS 项目 32+33 恶化更明显（+1.7±2.0 单位；95%置信区间 0.9，2.4），而继续接受金刚烷胺治疗的患者（“继续”组）恶化更不明显（+0.2±1.5 单位；95%置信区间-0.4，0.8；p=0.003）。次要观察指标证实了这一差异，因为停药组有更多的应答者、更多的 LID 停药、“ON”时间中麻烦性运动障碍的增加以及不自主运动量表评分的更大恶化。两组间 UPDRS 运动检查无差异，而照顾者评估的淡漠（apathy）和疲劳评分在随机接受安慰剂的患者中似乎更差。