Phase 2 Trial of Rivastigmine for Fall Prevention in Parkinson Patients

Summary and Comment |
January 25, 2016

Phase 2 Trial of Rivastigmine for Fall Prevention in Parkinson Patients

  1. Michael S. Okun, MD

Should we be giving cholinesterase inhibitors for walking and falling issues in Parkinson disease?

  1. Michael S. Okun, MD

Cholinergic deficiency has long been thought to be a large contributor to walking problems in Parkinson disease (PD). Researchers conducted the phase II, randomized, double-blind, placebo-controlled ReSPonD trial to test whether the acetylcholinesterase inhibitor rivastigmine can improve gait variability, a factor in risk for falls. Participants were nondemented patients from both community and hospital settings who had fallen at least once in the prior year but could walk unassisted for 18 meters. Rivastigmine or a placebo pill was titrated to 12 mg per day over 12 weeks, and then continued for a total of 32 weeks. The primary outcome variable was the difference in step-time variability in three conditions: normal walking, walking during a simple verbal-fluency task, and walking during a more complex verbal-fluency task. Of 65 patients randomized to each group, 59 in the placebo group and 55 in the rivastigmine group provided data.

After 32 weeks, the rivastigmine group had significantly lower step-time variability than the placebo group during normal walking (ratio of geometric means, 0.72) and during the simple dual task (0.79). Performance during the complex task did not differ significantly between the groups. The main adverse event was nausea (31% in rivastigmine group vs. 5% in placebo).


In patients with Parkinson disease and falling histories, gait variability improved significantly with rivastigmine during simple walking. However, the results were less impressive with a simple dual task, and the significance disappeared with a complex dual task. The exclusion of patients requiring walking aids further reduces the generalizability of the results. The effect of improving gait variability for longer time intervals and its impact on falls and fractures remain unknown. Most people unconsciously perform complex dual tasks during walking, so these findings, while interesting, are probably not compelling enough to change clinical practice.

Editor Disclosures at Time of Publication

  • Disclosures for Michael S. Okun, MD at time of publication Consultant / Advisory board National Parkinson Foundation; Tourette Syndrome Association Grant / Research support National Institutes of Health; National Parkinson Foundation; Michael J. Fox Foundation; Tourette Syndrome Association; Bachmann-Strauss Dystonia & Parkinson Foundation; Dystonia Medical Research Foundation Editorial boards National Parkinson Foundation; Parkinsonism and Related Disorders; Tremor and Other Hyperkinetic Movements; Journal of Clinical Movement Disorders Leadership positions in professional societies National Parkinson Foundation (National Medical Director); Tourette Syndrome Association (Co-Chair Medical Advisory Board); International Parkinson and Movement Disorder Society (International Executive Committee)


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