By Gene Emery



(Reuters Health) – An experimental extended-release version of the drug amantadine can reduce the duration of the involuntary dancing-like movements seen in people whose long-term use of levodopa has kept their Parkinson’s disease under control.

The results may help doctors walk a tightrope in treating the tremors and muscle rigidity of Parkinson’s itself, where the beneficial effects of levodopa wane over time, producing so-called “off” times. Efforts to shorten the off times by increasing the levodopa dose lead to the other unwanted movements, a condition known as levodopa-induced dyskinesia (LID).

LID arises in more than half of Parkinson’s patients who have taken levodopa for four to six years and in more than 90 percent of patients who have been on the drug for a decade. The disease itself affects nearly a million people in the U.S., according to the Parkinson’s Disease Foundation.

In the new study, when 58 patients were given placebo for 12 weeks, they improved by 8.0 points on a test designed to measure their symptoms that has a maximum score of 104. But for the 63 people on extended-release amantadine, the improvement was 15.9 points.

And when doctors looked at patients’ off times, they found amantadine decreased the duration by about 34 minutes per day compared to placebo recipients, who saw the duration of their unwanted movements increase by about 18 minutes.

“This would be the first medicine, if approved, to take care of the dyskinesia and the off times,” lead author Dr. Rajesh Pahwa, director of the Parkinson’s Disease and Movement Disorder Center at the University of Kansas Medical Center in Kansas City, told Reuters Health.

The study, known as EASE LID, did not compare this formulation of amantadine to other LID therapies, including immediate-release amantadine, which has to be taken two or three times a day. The manufacturer, California-based Adamas Pharmaceuticals, paid for the test. The long-acting version used in the current study is also known as ADS-5102.

“The results demonstrated that extended-release amantadine was well tolerated, safe, and effective for the treatment of LID,” Dr. Aparna Wagle Shukla of the University of Florida, Gainesville writes in an editorial in JAMA Neurology, where the study appears. “It remains to be established whether the benefits of this new pill will justify the cost.”

But the drug has side effects, including insomnia, agitation, constipation, dizziness and, most commonly, hallucinations, which were experienced by nearly one out of four patients. Those unwanted properties caused one in five patients to discontinue the drug, a rate three times higher than seen with placebo.

Immediate-release amantadine is not approved as a treatment for dyskinesia, but some doctors prescribe it anyway despite limited evidence, Pahwa said. Attempts to use nicotine, marijuana or the antiepilepsy drug levetiracetam as therapies have shown even less promise.

The experimental drug was given in the evening so blood levels would peak around noon, when LID symptoms are most likely to appear. The timing is also less likely to cause insomnia.

In addition to the hallucinations experienced by nearly a quarter of the drug recipients, other prominent side effect included swelling, dizziness, dry mouth, constipation and falls.

The researchers said the visual hallucinations were easily tolerated and didn’t affect a person’s normal function. Only one of the drug recipients reported a severe hallucination. Five of the 15 who reported hallucinations discontinued treatment.

“All Parkinson’s medicines in general can cause hallucinations,” Pahwa noted. With the experimental drug, “some can have hallucinations five minutes a day once a week. It’s something patients need to be aware of.”


SOURCE: JAMA Neurology online, June 12, 2017.


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