Drug Safety

, Volume 31, Issue 1, pp 79–94

Effects of Rivastigmine on Tremor and Other Motor Symptoms in Patients with Parkinson’s Disease Dementia

A Retrospective Analysis of a Double-Blind Trial and an Open-Label Extension


    • Department of NeurologyPhilipps University
  • Werner Poewe
    • Department of NeurologyMedical University Innsbruck
  • Erik Wolters
    • Research Institute Neurosciences Vrije Universiteit
  • Peter Paul De Deyn
    • Middelheim Hospital ZNAUniversity of Antwerp
  • Murat Emre
    • Istanbul Faculty of Medicine
  • Courtney Kirsch
    • ]Novartis Pharmaceuticals Corporation
  • Chuanchieh Hsu
    • ]Novartis Pharmaceuticals Corporation
  • Sibel Tekin
    • ]Novartis Pharmaceuticals Corporation
  • Roger Lane
    • ]Novartis Pharmaceuticals Corporation
Original Research Article

DOI: 10.2165/00002018-200831010-00007

Cite this article as:
Oertel, W., Poewe, W., Wolters, E. et al. Drug-Safety (2008) 31: 79. doi:10.2165/00002018-200831010-00007


Background and aim: Rivastigmine is now widely approved for the treatment of mild to moderately severe dementia in Parkinson’s disease (PDD). However, since anticholinergic drugs have a role in the management of tremor in patients with Parkinson’s disease (PD), concerns have been raised that the use of cholinergic drugs might worsen PD. The current analyses were performed to examine the potential of rivastigmine to affect tremor and other motor symptoms in patients with PDD.

Methods: The safety profile of rivastigmine was evaluated using a database from a 24-week, randomized, double-blind, placebo-controlled trial in 541 PDD patients (362 randomized to rivastigmine, 179 to placebo), and 334 PDD patients who subsequently entered an open-label 24-week extension on rivastigmine.

Results: During the double-blind trial, the adverse event (AE) of emerging or worsening tremor was reported in 10.2% of patients in the rivastigmine group, compared with 3.9% in the placebo group (p = 0.012). Tremor was most frequently reported during the titration phase of rivastigmine treatment, although this was not reflected in total motor Unified Parkinson’s Disease Rating Scale (UPDRS) part III scores. Dose dependence of this AE was not observed. At the end of the double-blind phase, six (1.7%) rivastigmine-treated patients had discontinued the study because of tremor. In the open-label extension in which all patients received rivastigmine, tremor was reported by 6.9% of patients: 3.8% and 12.2% of whom had previously received double-blind rivastigmine and placebo, respectively (p = 0.006), suggesting that first exposure to rivastigmine leads to a transient increase in tremor. Three (0.9%) of the 334 patients who entered the open-label extension phase discontinued because of tremor. Incidences of worse ning parkinsonism, bradykinesia and rigidity were all <5% in both treatment groups (all p-values not statistically significant, rivastigmine vs placebo). In the 48-week observation of rivastigmine treatment, there was no evidence of adverse long-term motor outcomes. Posthoc analysis showed that similar improvements in the symptoms of dementia, including the ability to perform activities of daily living, were seen regardless of whether exacerbation of tremor was reported during the study.

Conclusion: Rivastigmine did not induce clinically significant exacerbation of motor dysfunction in patients with PDD. Rest tremor incidence as an AE was a transient phenomenon during dose titration of rivastigmine. There was no indication that exposure to long-term rivastigmine was associated with a worsening of PD.

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© Adis Data Information BV 2008