Withdrawing amantadine in dyskinetic patients with Parkinson disease : The AMANDYSK trial

F. Ory-Magne, J.-C. Corvol, J.-P. Azulay, A.-M. Bonnet, C. Brefel-Courbon, P. Damier, E. Dellapina, A. Destee, F. Durif, M. Galitzky, T. Lebouvier, W. Meissner, C. Thalamas, F. Tison, A. Salis, A. Sommet, F. Viallet, M. Vidailhet, O. Rascol,
Neurology. 2013-12-26; 82(4): 300-307
DOI: 10.1212/WNL.0000000000000050

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

Withdrawing amantadine in dyskinetic patients with Parkinson disease: the

Ory-Magne F(1), Corvol JC, Azulay JP, Bonnet AM, Brefel-Courbon C, Damier P,
Dellapina E, Destée A, Durif F, Galitzky M, Lebouvier T, Meissner W, Thalamas C,
Tison F, Salis A, Sommet A, Viallet F, Vidailhet M, Rascol O; NS-Park CIC

Author information:
(1)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.

Comment in
Neurology. 2014 Sep 9;83(11):1035-6.
Neurology. 2014 Sep 9;83(11):1036.

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.

DOI: 10.1212/WNL.0000000000000050
PMID: 24371304 [Indexed for MEDLINE]

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