June 25, 2014
Levodopa Can Provide Better Mobility, Quality of
Life Than Alternatives

Oxford, UK—Levodopa may have been around for more than 50 years as a Parkinson’s disease (PD) therapy, but it still provides better mobility and a higher quality of life than two major alternatives—dopamine agonists (DAs) and monoamine oxidase type B inhibitors (MAOBIs), according to the largest-ever study of long-term treatment of the disease.

Background in the study, published recently by The Lancet, points out that levodopa remains the most widely used treatment for PD but that, after prolonged use, patients can develop dyskinesias and motor fluctuations. While the risk of those complications lessens with DAs or with MAOBIs, other side effects including nausea, hallucinations, edema, and sleep disturbance, are increased.

“Previous studies included too few patients, had short follow-up, and focused on the clinicians’ assessments of motor symptoms rather than asking patients how the drugs affected their overall quality of life. So, for many years there has been uncertainty about the risks and benefits of starting treatment with these different classes of PD drugs,” said the lead author, Professor Richard Gray from the University of Oxford.

The PD MED randomly assigned 1,620 patients recently diagnosed with PD to levodopa-sparing therapy (DA or MAOBI) or levodopa between November 9, 2000, and December 22, 2009. Over as many as seven years of follow-up, patients reported small but persistent benefits in mobility and quality of life with levodopa compared to the other drugs.

Despite more involuntary muscle spasms, patients in the levodopa group also reported significantly better scores on the activities of daily living, stigma, cognition, communication, and bodily discomfort scales than those in the other therapy groups.

“Although the differences in favor of levodopa are small, when you consider the short- and long-term benefits, side-effects, quality of life for patients, and costs, the old drug levodopa is still the best initial treatment strategy for most patients,” Gray suggested, adding, “In current clinical practice, most patients younger than 70 years are treated initially with a DA to avoid levodopa-related motor complications. However, we found levodopa better than the more expensive DAs at all ages.”

In addition to the small benefits from therapy initiation with levodopa, the authors also report that “MAOBI as initial levodopa-sparing therapy was at least as effective as dopamine agonists.”

As the largest drug trial ever performed in Parkinson's disease, PD MED “is likely to change clinical practice worldwide, with the majority of patients from now on starting therapy with levodopa,” according to researcher Professor Carl Clarke of the University of Birmingham, UK.

Writing in a linked comment, Anthony Lang, MD, and Connie Marras, MD, PhD, from Toronto Western Hospital in Ontario, Canada, point out, “PD MED provides reassuring data showing that in most patients with Parkinson’s disease, who have an older age of onset, how treatment is initiated generally does not matter because outcomes are very similar…Finally, and perhaps most importantly, the results of this study will help to persuade physicians and reassure patients that the fears that have served as the groundwork in establishing levodopa phobia—that often results in patients experiencing unnecessary and easily managed disability and reduction in quality of life in the early years of their disease—are unfounded.”


U.S. Pharmacist Social Connect