title: Withdrawing amantadine in dyskinetic patients with Parkinson disease: the AMANDYSK trial.
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.
  
  
  CONCLUSIONS
  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.
  
  
  METHODS
  This article provides Class II evidence that in patients with PD, withdrawing amantadine significantly aggravates LID in a median time of 7 days.
authors.affiliation: 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.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Ory-Magne
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Corvol
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Azulay
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Bonnet
authors.forename: Christine
authors.initials: C
authors.lastname: Brefel-Courbon
authors.forename: Philippe
authors.initials: P
authors.lastname: Damier
authors.forename: Estelle
authors.initials: E
authors.lastname: Dellapina
authors.forename: Alain
authors.initials: A
authors.lastname: Destée
authors.forename: Franck
authors.initials: F
authors.lastname: Durif
authors.forename: Monique
authors.initials: M
authors.lastname: Galitzky
authors.forename: Thibaud
authors.initials: T
authors.lastname: Lebouvier
authors.forename: Wassilios
authors.initials: W
authors.lastname: Meissner
authors.forename: Claire
authors.initials: C
authors.lastname: Thalamas
authors.forename: François
authors.initials: F
authors.lastname: Tison
authors.forename: Alexandrine
authors.initials: A
authors.lastname: Salis
authors.forename: Agnès
authors.initials: A
authors.lastname: Sommet
authors.forename: François
authors.initials: F
authors.lastname: Viallet
authors.forename: Marie
authors.initials: M
authors.lastname: Vidailhet
authors.forename: Olivier
authors.initials: O
authors.lastname: Rascol
mesh_terms: D000368:Aged; D000547:Amantadine / Q000627:therapeutic use*; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007980:Levodopa / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa; D000547:Amantadine