title: Long-term safety of rivastigmine in parkinson disease dementia: an open-label, randomized study.
abstract: OBJECTIVE
  This study investigated the long-term safety of rivastigmine (12 mg/d capsules, 9.5 mg/24 h patch) and effects on motor symptoms in patients with mild-to-moderately severe Parkinson disease dementia.
  
  
  METHODS
  This was a 76-week, prospective, open-label, randomized study in patients aged 50 to 85 years. Primary outcomes included incidence of, and discontinuation due to, predefined adverse events (AEs) potentially arising from worsening of Parkinson disease motor symptoms with capsules. Secondary outcomes included frequency of AEs/serious AEs. Efficacy outcomes included Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), Neuropsychiatric Inventory (NPI-10), and Mattis Dementia Rating Scale (MDRS).
  
  
  RESULTS
  Five hundred eighty-three patients were randomized to rivastigmine capsules (n = 295) or patch (n = 288). Incidence of predefined AEs was 36.1% for capsules, 31.9% for patch; discontinuation due to worsening of motor symptoms was 4.4% and 2.4%, respectively. Most common AEs were nausea (capsules, 40.5%; patch, 8.3%), tremor (24.5%; 9.7%), fall (17.0%; 20.1%), vomiting (15.3%; 2.8%), and application site erythema (0%; 13.9%). Significant efficacy in favor of capsules was observed at weeks 24 to 76 on MDRS; 24 and 76 on NPI-10; weeks 52 and 76 on ADCS-ADL. In patients with Mini-Mental State Examination (MMSE) greater than 21, no differences in efficacy on MDRS and ADCS-ADL were observed at any time point; significant differences in favor of capsules were maintained in patients with MMSE less than or equal to 21.
  
  
  CONCLUSIONS
  This study supports the long-term safety of rivastigmine in Parkinson disease dementia. The rate of worsening of motor symptoms was in the range expected due to the natural progression of Parkinson disease, no new or unexpected safety issues emerged in the long-term.
authors.affiliation: *Department of Neurology, Behavioural Neurology and Movement Disorders Unit, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey; †Department of Neurology, Medical University Innsbruck, Innsbruck, Austria; ‡Middelheim Hospital, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; §Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands; ║Neurodegenerative Diseases Centre, Department of Medicine, University of Salerno, Italy; ¶Department of Neurology, Movement Disorders Unit, Hospital de Sant Pau (IIB-Sant Pau) and CIBERNED, Universitat Autònoma de Barcelona, Barcelona, Spain; #Québec Memory and Motor Skills Disorders Research Center, Clinique Sainte Anne, Québec, Canada; **Division of Neurodegenerative Diseases, Department of Neurology, Dresden University of Technology, Dresden, Germany; ††Department of Neurology, Hospital de Clinicas, University of Buenos Aires, Argentina; ‡‡Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, United Kingdom; §§Service De Neurologie CHU, Clermont-Ferrand, France; ║║Parkinson's Disease and Movement Disorder Center, University of Kansas Medical Center, Kansas City, KS; ¶¶Novartis Pharma AG, Basel, Switzerland; and ##Novartis Pharmaceuticals Corporation, East Hanover, NJ.
authors.forename: Murat
authors.initials: M
authors.lastname: Emre
authors.forename: Werner
authors.initials: W
authors.lastname: Poewe
authors.forename: Peter Paul
authors.initials: PP
authors.lastname: De Deyn
authors.forename: Paolo
authors.initials: P
authors.lastname: Barone
authors.forename: Jaime
authors.initials: J
authors.lastname: Kulisevsky
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Pourcher
authors.forename: Teus
authors.initials: T
authors.lastname: van Laar
authors.forename: Alexander
authors.initials: A
authors.lastname: Storch
authors.forename: Federico
authors.initials: F
authors.lastname: Micheli
authors.forename: David
authors.initials: D
authors.lastname: Burn
authors.forename: Frank
authors.initials: F
authors.lastname: Durif
authors.forename: Rajesh
authors.initials: R
authors.lastname: Pahwa
authors.forename: Francesca
authors.initials: F
authors.lastname: Callegari
authors.forename: Nadia
authors.initials: N
authors.lastname: Tenenbaum
authors.forename: Christine
authors.initials: C
authors.lastname: Strohmaier
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D003704:Dementia / Q000188:drug therapy* / Q000209:etiology; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D007391:International Cooperation; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D017063:Outcome Assessment, Health Care; D010300:Parkinson Disease / Q000150:complications / Q000188:drug therapy* / Q000523:psychology; D010349:Patient Compliance; D048448:Phenylcarbamates / Q000627:therapeutic use*; D011788:Quality of Life; D000068836:Rivastigmine; D013997:Time Factors; D057968:Transdermal Patch; D016896:Treatment Outcome
chemical_list: D004337:Drug Carriers; D018696:Neuroprotective Agents; D048448:Phenylcarbamates; D000068836:Rivastigmine