Article Text

Download PDFPDF
Research paper
Rivastigmine in apathetic but dementia and depression-free patients with Parkinson's disease: a double-blind, placebo-controlled, randomised clinical trial
  1. David Devos1,2,3,
  2. Caroline Moreau2,3,
  3. David Maltête4,
  4. Romain Lefaucheur4,
  5. Alexandre Kreisler2,5,
  6. Alexandre Eusebio6,
  7. Gilles Defer7,
  8. Thavarak Ouk1,3,
  9. Jean-Philippe Azulay6,
  10. Pierre Krystkowiak8,9,
  11. Tatiana Witjas6,
  12. Marie Delliaux2,
  13. Alain Destée2,5,
  14. Alain Duhamel10,
  15. Régis Bordet1,3,
  16. Luc Defebvre2,3,
  17. Kathy Dujardin2,3
  1. 1Department of Medical Pharmacology, Lille University Hospital, Lille, France
  2. 2Department of Movement Disorders and Neurology, Lille University Hospital, Lille, France
  3. 3EA 1046/EA 4559, Lille Nord de France University, Lille, France
  4. 4Department of Neurology and INSERM CIC-CRB 0204, Rouen University Hospital, Rouen, France
  5. 5INSERM U837/6 JPARC, Lille, France
  6. 6Department of Neurology and Movement Disorders –Timone University Hospital and Institut de Neurosciences de la Timone, Marseille, France
  7. 7Department of Neurology and Movement Disorders, Caen University Hospital, Caen, France
  8. 8EA 4559—Laboratoire de Neurosciences Fonctionnelles et Pathologie (LNFP), UFECAP Department of Neurology and Movement Disorders, University of Picardy Jules Verne (UPJV), SFR CAP-Santé (FED 4231), Amiens University Hospital, Amiens, France
  9. 9Department of Neurology and Movement Disorders, Amiens University Hospital, Amiens, France
  10. 10Department of Biostatistics, Lille Nord de France University and Lille University Hospital, Lille, France
  1. Correspondence to Dr Devos David, Département de Pharmacologie Médicale, Université Lille Nord de France, CHRU de Lille, Lille F-59037, France; david.devos{at}


Background Even with optimal dopaminergic treatments, many patients with Parkinson's disease (PD) are frequently incapacitated by apathy prior to the development of dementia. We sought to establish whether rivastigmine's ability to inhibit acetyl- and butyrylcholinesterases could relieve the symptoms of apathy in dementia-free, non-depressed patients with advanced PD.

Methods We performed a multicentre, parallel, double-blind, placebo-controlled, randomised clinical trial (Protocol ID: 2008-002578-36; reference: NCT00767091) in patients with PD with moderate to severe apathy (despite optimised dopaminergic treatment) and without dementia. Patients from five French university hospitals were randomly assigned 1:1 to rivastigmine (transdermal patch of 9.5 mg/day) or placebo for 6 months. The primary efficacy criterion was the change over time in the Lille Apathy Rating Scale (LARS) score.

Finding 101 consecutive patients were screened, 31 were eligible and 16 and 14 participants were randomised into the rivastigmine and placebo groups, respectively. Compared with placebo, rivastigmine improved the LARS score (from −11.5 (−15/−7) at baseline to −20 (−25/−12) after treatment; F(1, 25)=5.2; p=0.031; adjusted size effect: −0.9). Rivastigmine also improved the caregiver burden and instrumental activities of daily living but failed to improve quality of life. No severe adverse events occurred in the rivastigmine group.

Interpretation Rivastigmine may represent a new therapeutic option for moderate to severe apathy in advanced PD patients with optimised dopaminergic treatment and without depression dementia. These findings require confirmation in a larger clinical trial. Our results also confirmed that the presence of apathy can herald a pre-dementia state in PD.

Registration reference: NCT00767091.

  • 79 characters (subtitle:61 characters)
  • running title:47 characters
  • 3521 words (abstract:237 words)
  • Tables:3
  • Figure:1 (flowchart)
  • references:29

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.