Parkinson's treatment: Levodopa infusion more effective than pills

Evan Walker
Evan Walker TheMediTary.Com |
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Could changing the delivery of one of the most commonly used Parkinson’s drugs improve its effectiveness? Image credit: VICTOR TORRES/Stocksy.
  • Parkinson’s disease is the fastest growing neurological condition in the world, and the reasons for this are unclear.
  • One of the main drugs offered to people with Parkinson’s disease is levodopa, which helps with symptoms affecting movement.
  • A global team of researchers have now shown that the efficacy of the drug can be improved by being administered continuously via a pump, rather than orally, which is how it is usually taken.

Parkinson’s disease affects over 8.5 million individuals worldwide, and prevalence has doubled in the past 25 years.

It is a progressive, degenerative condition characterised by loss of the dopaminergic cells in the substantia nigra part of the brain.

It causes a range of symptoms, including problems with motor control, shakes, rigidity, slow movement, balance problems, sensory problems depression and anxiety.

Levodopa is the most effective drug available at present for treating the motor control aspect of the condition. It is a precursor to dopamine and increases signalling in the brain, but it becomes less effective over time as the condition progresses.

There is no cure for Parkinson’s disease at present.

Other drugs are available, as well as a surgical technique known as deep brain stimulation, but this comes with its own set of risks.

While therapy for Parkinson’s disease can be beneficial in managing symptoms and improving quality of life, there are several limitations and challenges associated with these treatments, said Dr. Daniel Truong, neurologist and medical director of the Truong Neuroscience Institute at MemorialCare Orange Coast Medical Center in Fountain Valley, CA, and editor-in-chief of the Journal of Clinical Parkinsonism and Related Disorders.

Speaking of treatments, he told Medical News Today:

“Medications used to treat Parkinson’s disease, such as levodopa and dopamine agonists, can lose effectiveness over time, leading to the development of motor fluctuations and dyskinesias. Side effects of medications can be significant and may include nausea, vomiting, hallucinations, orthostatic hypotension, and impulse control disorders.“

“Deep brain stimulation (DBS) surgery, while effective for many patients, is invasive and carries risks such as infection, stroke, hemorrhage, and hardware complications. Not all patients are suitable candidates for DBS surgery, and the procedure may not provide significant benefit for some individuals,” he explained.

Other potential treatments included physical therapy, occupational therapy and speech therapy, all of which could be tailored to an individual’s needs.

Previous studies have suggested that continuous infusion with Levodopa could improve the drug’s efficacy in controlling movement problems.

Now, an international team of researchers has published results of a Phase III trial which compared the efficacy of oral levodopa to continuous subcutaneous infusion in The Lancet Neurology.

Participants were recruited to the trial at 117 sites in 16 countries globally, and were eligible if they had over 2.5 hours a day negatively affected by dyskinesia, problems with movement and motor control.

The 243 participants who completed the study first had their optimum dosage of oral levodopa determined over a period of 4–6 weeks, and then had their optimum dosage for subcutaneous infusion of the drug over the following 4–6 weeks.

Once researchers had determined the optimum dosages for individual participants, participants were assigned to either the oral or subcutaneous infusion branch of the study for 12 weeks.

Researchers deployed a double blind, “double dummy” design for the trial, to prevent bias from occurring. In order to do this all participants had an infusion device that was either delivering levodopa or a placebo.

All participants would have continued to take oral medication, and if they were receiving levodopa via their infusion device they were given placebo “dummy” pills, and if they were receiving a placebo through their device they were given their optimised dose of oral levodopa–carbidopa.

Participants also completed a home diary in which they recorded the effects of medication on their symptoms every 30 minutes, after undergoing training in how to do this. Participants did not know which group they belonged to, to avoid bias in the recording of their symptoms.

The dosage of other Parkinson’s drugs participants were on remained stable during the 12 week period of the trial.

Researchers discovered that continuous infusion of levodopa was associated with a reduction in “troublesome dyskinesia” of around 1.7 hours a day, more than participants on oral levodopa.

They also performed better on four out of nine disease ratings scales that capture disability from Parkinson’s disease symptoms.

Participants had the option to continue treatment with the subcutaneous infusion device as part of a further clinical trial, authors confirmed. Results on that have not yet appeared in a peer-reviewed journal.

The study authors propose that the improvement seen in patients who had continuous infusion could be helpful as a next step intervention for people who want to avoid surgery.

They make it clear that the study only looked at this single drug, and did not compare it to other drugs. A significant number of participants experienced side effects, mainly to do with reactions at the device site.

One of the reasons for the improvement could be dosage of the drug at night, which is otherwise difficult to achieve without disrupting sleep, the study authors said.

There are other reasons why using this device could result in better outcomes, Dr. Mary Feldman, a neurologist for Dartmouth Health who was not involved in the research told MNT.

“Levodopa heavily relies on a stomach to be empty of other food and proteins essentially to work well. So this medication is absorbed subcutaneously and patients kind of forget about it,” she explained.

There were also benefits for patients’ lifestyle with this kind of device, she added.

“They kind of have freedom from having to always rely on you know taking pills and watching the clock so that’s nice. Also, they don’t have this continuous yo-yo effect of you know, taking a medicine, waiting for it to kick in and then having it wear off,“ Feldman noted.

The device also offered a less invasive option for continuous delivery of levodopa than one that already exists, called a PEG-J infusion.

“It is a continuous infusion of levodopa but it involves, you know, a tube in the stomach. And so it’s not very pleasant for patients so this will be much less invasive. So that’s why it’s also very appealing,” Feldman explained.

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