One of the common dreams shared by Parkinson’s disease patients around the globe is the possibility of living a pill free existence. One cannot blame the Parkinson’s disease patient or caregiver for dreaming big. A single day in Parkinson’s disease shoes is likely to reveal the need for dozens of pills administered day and night. In many cases, pills are taken as frequently as every hour or two. If you ask a Parkinson’s disease patient to place an entire pill regimen for the day into the palms of their hands, there is a better than average chance he or she will not be able to hold all of them. Previously, there was a hope that deep brain stimulation may have offered the highly sought after “pill free existence,” however over two decades into its history, it is clear that in the majority of cases, medications will still be required. There is however, another treatment strategy on the horizon. A strategy that offers the possibility of constant stimulation of the brain’s dopamine receptors through the use of a continuous dopamine infusion pump technology. In this month’s issue of Lancet Neurology the first randomized controlled trial of a continuous pump infusion technology for Parkinson’s disease has been published (online before print).
The trial utilized an intrajejunal (i.e. a tube inserted in the small intestine) levodopa-carbidopa intestinal gel pump infusion strategy, and it was designed to collect safety and effectiveness data. The study was carefully conducted and was double-blind (neither the patients nor the raters knew what was administered) and randomized. It was conducted in 26 centers including Germany, New Zealand, and the US. Participants were randomized (1:1) to “immediate-release oral levodopa-carbidopa pills plus a placebo intestinal gel infusion or to levodopa-carbidopa intestinal gel infusion plus oral placebo pills.” It is important to remember that everyone in the study received a pump, but half of the patients did not receive active therapy (through the continuous pump infusion). The authors were most interested in improving the amount of time spent in the “off state” following 4 months of therapy. “Off” time improved by 4 hours in the pump group versus 2.1 hours in the pill group. The amount of “on” time without troublesome dyskinesia was better in the pump group when compared to the pill group (4.1 vs. 2.2 hours).
The pump is approved and available in 43 countries. The United States has lagged behind the world in adopting this new approach to Parkinson’s disease therapy. However, in defense of the U.S.A. and the FDA, prior to the publication of the current pump trial, all previous results were based on uncontrolled evidence. The benefits of the pump have been clearly demonstrated. In this population of fluctuating patients, the data would suggest that the pump out-performs standard medical therapy. The study did not enroll patients with severe dyskinesia, and it is unclear how the continuous infusion pump will perform in more severe and more disabled Parkinson’s disease patients.
One of the major drawbacks to the pump approach is the need for a percutaneous gastrojejunostomy (a small feeding tube). These types of tubes can serve as nidus points for infections and other complications, and in the current study, device complications were present in 89% of subjects. The complications were addressable in most cases, and were reported as lower than in previous pump trials.
Patients should be aware that the current version of the pump requires wearing an external device, and it also requires changing a dopamine cassette once or twice a day. The dopamine cassettes are a little smaller than a cellular phone, and usually last about 14-16 hours. Some patients will require two cassettes, and some will need additional medications during the bedtime hours. The pumps require continuous maintenance and programming by a qualified professional. The tube connected to the stomach also requires constant monitoring for infection.
If the continuous infusion approach receives FDA approval one important step will be to compare its effectiveness to that of deep deep brain stimulation (DBS). Patient selection for pumps versus DBS will be an immediate and critical unmet need. One question will be whether the pump technology can help debilitated patients with and without cognitive dysfunction who may be excluded from DBS.
Patients should be aware that pumps are powerful symptomatic therapies, but not cures; and in most cases the continuous infusion pump will not address the dopamine resistant symptoms of walking, talking, and thinking. Pumps have not been shown to delay disease progression. The good news for the Parkinson’s disease community is that for a subset of patients a “pill free existence” may be on the horizon.
You can find out more about our National Medical Director, Dr. Michael S. Okun, by also visiting the Center of Excellence, University of Florida Health Center for Movement Disorders and Neurorestoration. Dr. Okun is also the author of the Amazon #1 Parkinson's Best Seller 10 Secrets to a Happier Life and 10 Breakthrough Therapies for Parkinson's Disease.