As Parkinson's disease (PD) progresses, the benefits of oral medications fade faster and faster. This wearing off happens as the brain loses the ability to store dopamine. Patients may benefit from an alternate method of delivery—carbidopa/levodopa enteral suspension (Duopa™)—available at Penn Neurology.
The On/Off Phenomenon
"The brain cells that make dopamine, store it and regulate dopamine levels degenerate in Parkinson's disease," says Meredith A. Spindler, MD, associate clinical director of Penn Parkinson's Disease and Movement Disorders Center (PD&MDC) and associate professor of clinical neurology.
A dopamine spike—the "on" period—happens after patients take carbidopa/levodopa medication (synthetic dopamine), bringing relief of Parkinson's motor symptoms. But soon, enzymes break down the dopamine, and the brain hasn't stored any of it.
Patients' uncomfortable Parkinson's symptoms return during these "off" periods, causing limited mobility and tremor. The change in dopamine levels can also lead to involuntary movements called dyskinesias, which can happen when "on" or when "wearing off". Taken together, these complications of dopamine therapy are called "motor fluctuations."
Carbidopa/Levodopa Enteral Suspension: The Duopa Pump
Duopa helps prevent wearing off, motor fluctuations and dyskinesias by providing 16-hour continuous medication delivery. The device pumps carbidopa/levodopa gel directly into the small intestine, where it is quickly absorbed into the blood.
The device requires a PEG-J tube, which is implanted via a percutaneous endoscopic gastronomy procedure. The patient then sees their neurologist to start the pump and determine the appropriate dosing. Once dosing is determined patients insert a new cassette of carbidopa/levodopa gel into the pump each morning and hook it up to their PEG-J tube to steadily receive medication.
Patients self-administer the following doses on a daily basis:
- Morning infusion (a larger dose to start the day strongly "on")
- Continuous infusion (a lower dose at a steady rate)
- Supplemental dose (as needed during unexpected "off" periods)
"Many patients don't know about Duopa, or they don't want the burden of a tube and a pump, but the benefit of it is real," highlights Dr. Spindler. "People go from taking pills every two or three hours and only getting an hour of benefit out of each dose to not taking pills at all and just being 'on' the whole day."
When to Recommend Duopa for Motor Fluctuations and Dyskinesias
When other classes of PD medications have failed to control the motor fluctuations, providers should discuss additional treatment options like Duopa. The same patients also may benefit from deep brain stimulation (DBS).
"Ideally, patients should be offered both a medication pump and DBS at the same time and should be part of the decision-making process," says Dr. Spindler. Specialists at Penn PD&MDC, one of 51 Parkinson's Foundation Centers of Excellence in the world, offer both therapies.
DBS can significantly reduce motor fluctuations and medication burden. However, some people may not want DBS, are not surgical candidates or received DBS in the past but still have motor fluctuations. In these cases, patients may benefit from Duopa or another soon-to-be-approved subcutaneous pump.
Infusion Therapies for PD on the Horizon
Penn neurologists successfully trialed two more medication pumps for PD, which they anticipate will receive Food and Drug Administration (FDA) approval for use within a year or two:
- Subcutaneous carbidopa/levodopa pump
- Subcutaneous apomorphine pump
These infusion therapies for PD work similarly to an insulin pump, where medication gets delivered through a cannula and absorbed into the fatty tissue under the skin. Compared to Duopa, these pumps do not require surgery.
"The additional benefit is that a lot of people struggle with food interfering with the absorption and efficacy of their oral medication, leading to dosage failures," says Dr. Spindler. "If medication is absorbed subcutaneously, you eliminate this interference. Patients can eat whatever they want, whenever they want, and not have to worry about timing their meals around their medications."
Subcutaneous Carbidopa/Levodopa Pump
Two companies have manufactured subcutaneous pumps that infuse either carbidopa-levodopa directly or a pro-drug of carbidopa-levodopa. These pumps prevent wearing off by providing continuous delivery of the gold-standard PD medication. Penn neurologists have studied their use in clinical trials, but the pumps have not yet received FDA-approval.
Depending on the manufacturer, patients may need to change the subcutaneous cannula every one to three days and may have one or two infusion sites. Patients may also change the syringe of liquid medication more frequently than the infusion sites, depending on their total daily dose.
Subcutaneous Apomorphine Pump
Apomorphine, a dopamine agonist, has been successfully used in PD medication regimens for many years. The FDA approved apomorphine rescue injections for PD in 2004. Providers in Europe have offered both apomorphine rescue injections and subcutaneous infusions since 1995.
With the apomorphine pump, patients will change the syringe and the infusion site daily. Patients will most likely also need oral carbidopa/levodopa, but the combined therapies will minimize wearing off.
"It remains to be seen how these subcutaneous pumps are going to work for patients in real-world clinical practice," notes Dr. Spindler. "But movement disorders specialists at Penn will likely start prescribing them right away. We have patients waiting for them."
Additional Resources from Penn Parkinson's Disease and Movement Disorders Center