Rivastigmine for minor visual hallucinations in Parkinson's disease: A randomized controlled trial with 24 months follow-up

Brain Behav. 2021 Aug;11(8):e2257. doi: 10.1002/brb3.2257. Epub 2021 Jul 21.


Background: Visual hallucinations are common in patients with Parkinson's disease and represent probably the major independent predictor for cognitive deterioration and nursing home placement.

Objective: To investigate if treatment of minor visual hallucinations in Parkinson's disease with rivastigmine delays the progression to psychosis.

Methods: A multicenter, randomized, double-blind, placebo-controlled trial was conducted which aimed to recruit 168 patients with Parkinson's disease reporting minor visual hallucinations 4 weeks before it. Important exclusion criteria were Parkinson's disease dementia, current delirium, and treatment with antipsychotics or drugs that have significant anti-cholinergic side effects. Subjects were randomized to rivastigmine capsules, 3-6 mg twice a day, or placebo for 24 months. The primary outcome was the time to Parkinson's disease psychosis, which was defined as the need to start with antipsychotics.

Results: The trial was stopped prematurely because of slow recruitment. Ninety-one patients were randomized: 46 patients were assigned to rivastigmine and 45 patients to placebo. No effect of rivastigmine could be demonstrated on the transition time to psychosis or dementia during the 24-month follow-up period. After 6 months of study treatment, cognition, mood, motor performance, and non-motor performance did not differ significantly between the rivastigmine-group and the placebo-group.

Conclusions: Because the study was terminated early, it was insufficiently powered to properly evaluate the primary outcome. The limited data of the study favor a wait and see approach instead of early treatment with rivastigmine in PD patients with minor VH.

Keywords: Parkinson's disease; cholinesterase inhibitors; hallucinations; psychosis; randomized controlled trial.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cholinesterase Inhibitors
  • Follow-Up Studies
  • Hallucinations / drug therapy
  • Humans
  • Parkinson Disease* / complications
  • Parkinson Disease* / drug therapy
  • Phenylcarbamates
  • Rivastigmine


  • Cholinesterase Inhibitors
  • Phenylcarbamates
  • Rivastigmine