This public relations news release describes the results of a small, randomized, double-blind, placebo-controlled trial that suggests rivastigmine, a drug commonly prescribed to Alzheimer’s patients, might also be useful in reducing the risk of falls in people with Parkinson’s disease. The drug is a cholinesterase inhibitor which binds to and inactivates the enzyme acetylcholinesterase.The drug is believed to work by preventing the loss of acetylcholine, a chemical associated with concentration. Because the study was small with just 130 patient volunteers, it is too early to draw a conclusion about the drug’s benefit to people with Parkinson’s. While the idea and the results are quite interesting and novel, there is some unjustified hype in the news release.
Parkinson’s disease patients are prone to falls due to the disease’s hallmark tremors, slowness in gait and muscle rigidity. Falls are a frequent complication of Parkinson’s because of their potentially serious consequences (bone fractures, need for surgery, hospitalizations and even death). Fall prevention, therefore, is one of the main goals in managing this condition. If researchers can prove in a larger study that an existing drug can safely and effectively reduce the risk of falls among Parkinson’s disease patients it could improve their quality of life. The National Institute of Neurological Disorders and Stroke estimates that at least 500,000 American’s have Parkinson’s disease, with about 50,000 new cases diagnosed each year. In the UK, where the study was conducted, about 127,000 currently live with Parkinson’s.
The release doesn’t mention the drug’s cost but we won’t dock points for that omission since the release is from the UK where cost would be less of a concern for readers than it is in the U.S. This drug is common enough in the United States and is available in generic form.
The benefits are vaguely described in the release as being a 45% reduced risk in falling and becoming “considerably steadier when walking.” We’d like to see more quantification of the benefits, and more clarity, particularly an explanation of what “considerably” actually means. Did the researchers measure steadiness — there are different tools for the measurement of postural and motor steadiness — or did they just report the number of falls? In addition, does the 45% mean that 58 of the 130 patients taking part didn’t experience falls during the 8-month study period but that the other 55% (71 volunteers) continued to experience falls? The release isn’t clear about what a 45% reduced risk means and what the actual numbers of falls were in each group.
The release doesn’t mention any harms or side effects but some commonly reported adverse events associated with rivastigmine include dizziness and nausea. It can also cause drowsiness and fatigue which in some patients might actually increase the risk of falling. In addition, this drug has potential interactions with commonly prescribed drugs for elderly patients (such as aspirin, some beta blockers, NSAIDs, and medications for urinary incontinence, among others). This is noteworthy because Parkinson’s disease patients tend to be on multiple medications, increasing the likelihood of falls and of possible drug interactions.
The study is described as a randomized trial involving only Parkinson’s patients that had taken a fall within the past year. Half the group was given rivastigmine and half were given placebo over eight months. The researchers would have been better served if the news release had noted that the study was randomized, double-blind and placebo-controlled — the highest level of rigor in clinical trials.
No disease mongering here.
The release states that the study was funded by the Parkinson’s UK organization. When we looked at the published study we noted that the second author describes a conflict of interest with a company that manufactures fall risk assessment tools: “SRL declares that the FallScreen fall risk assessment tool is commercially available through Neuroscience Research Australia (NeuRA); any profits from sales of the assessment are shared equally between the inventor (SRL), the falls and balance research group at NeuRA, and the NeuRA central fund. All other authors declare no competing interests.” In addition, the charity’s website states that about 0.5% of its income comes from pharmaceutical companies but that “Our industry supporters don’t have any input into the content of our information.” While not critical, because these connections may not have any relationship to the pharmacological intervention, it would have been nice to have that spelled out.
While there do not appear to be any pharmacological treatments specifically for preventing falls in Parkinson’s patients, there are non-pharmacological approaches to fall prevention including certain exercises, making adjustments to home environments, modification of medications and multi-pharmacy, walking aids, and more. The release does not mention these. In addition, the drug amantadine (aka Symmetrel) has been used to address muscle rigidity (which can lead to falls) in Parkinson’s disease patients.
The release notes that the drug is already available as a treatment for Alzheimer’s disease patients.
It’s stated in the release that this is the first study to show that rivastigmine can improve movement in Parkinson’s patients. According to the lead investigator, “rivastigmine works to treat dementia by preventing the breakdown of acetylcholine, however our study shows for the first time that it can also improve regularity of walking, speed, and balance.”
Parkinson’s is widely known to be associated with dopamine anomalies, and the idea that other neurotransmitters, such as acetylcholine, can directly affect parkinsonism symptoms, is novel. Most other neurotransmitter drugs in Parkinson’s work to modify or increase the effects of dopamine and have no direct effects on the specific symptoms of Parkinson’s. The study itself states that this was “the first randomised controlled trial to examine the effect of rivastigmine on gait stability and falls in Parkinson’s disease.”
The lead investigator of the research, one of two medical professionals quoted in the release, goes overboard in calling the study findings “a real breakthrough in reducing the risk of falls for people with Parkinson’s.” Parkinson’s UK’s research director – as well as the study itself — takes a more measured approach in summarizing the study’s impact. Dr. Arthur Roach is quoted in the release saying the study shows “there may be” existing drugs that can help prevent falls and that the research “takes us a step closer to improving quality of life and finding better treatment’s for people with Parkinson’s.” That’s a much more measured and accurate description than calling it this small and preliminary study a “breakthrough.”
It also seems inappropriate to bring a patient testimonial into the mix as this release does. It quotes a patient who has Parkinson’s who experienced a fall who says the potential to find a treatment that prevents falls would allow her to have surgery for a fractured hip and give her confidence to go shopping without having to “constantly rely on the goodness of strangers to pick me up when I fall.”
Also, the actual title of this study, “Rivastigmine for gait stability in patients with Parkinson’s (ReSPonD): a randomised, double-blind, placebo-controlled, phase 2 trial” clearly mentions that this is preliminary, but including the ‘phase 2 trial’ in the title. This is not mentioned anywhere in the release and may lead readers to believe this process is farther along than it really is.