Clinical Trial Shows Levodopa is Still Best Treatment for Parkinson’s Disease



Clinical Trial Shows Levodopa is Still Best Treatment for Parkinson’s Disease


The results of a long term, open label clinical trial took place in the United Kingdom has shown that people with PARKINSON’S DISEASE had a better long-term benefit from levodopa than from other forms of treatment.  Principal investigator for this seven-year study was Dr. Richard Gray, who was the director of the University of Birmingham Clinical Trials Unit but is now a professor at University of Oxford.


The trial was designed to allow doctors treating people newly diagnosed with PARKINSON’S DISEASE freedom to begin treatment with which ever drug they preferred, based on the patient’s own symptoms and medical status.  Medications used included dopamine replacement with levodopa, dopamine agonists such as ropinerole or pramipexole or a monoamine oxidase type B inhibitor like selegiline or rasagiline.  If symptom management was not achieved with initial treatment, doses could be increased or levodopa used as an adjunct or medication could be changed from agonist to levodopa.


There have always been questions in the minds of both patients and their doctors about which is the best way to begin treatment for PARKINSON’S DISEASE.  Some thought that using levodopa early in the treatment process would limit its effectiveness later in the disease process or even lead to faster progression of the symptoms. Initial treatment with levodopa has often been found in other studies to induce dyskinesias making early treatment of PARKINSON’S symptoms with dopamine agonists of MAO-B inhibitors the first choice.  But dopamine agonists also have a high incidence of troublesome side effects such as sleep disturbance or compulsive behaviors and lack of impulse control.  This study followed 1620 patients for seven years to study the benefits and risks as well as the improvement in quality of life of the patients for both short term and long term treatment options.


An early discovery in this study was that treatment that began with monoamine oxidase type B Inhibitor was as effective as treatment that began with dopamine agonists.  They also found that patients were more likely to discontinue their treatment with MAO-B inhibitors or dopamine agonists than patients taking levodopa.  These treatments were discontinued usually due to quality of life issues or side effects that interfered with other aspects of the patients’ lives.  Researchers used a quality of life scale (the PDQ- 39) to evaluate patient responses that were not measured by clinical evaluation scales.


After seven years of treatment, patients that had been started with levodopa therapy were doing only slightly better on scales of mobility. They were also more likely to develop dyskinesias.  Patients on levodopa also rated their satisfaction with activities of daily living, cognitive abilities, communication skills and pain levels as being slightly better than the patients on agonists.


Study researchers believe this study dispels the thought that early treatment with levodopa limits its effectiveness later in the disease process.  While the improvement and benefit was very small in the levodopa group, the difference in outcomes may have been dependent on the adverse effects of the dopamine agonists. Levodopa appears to maintain its effectiveness over time, however the risk of motor complications such as dyskinesias still remains. The results of this study may also be somewhat hampered because the research studied subjects over age 70.  Younger onset subjects may have different responses leading to other outcomes.


For PARKINSON’S patients and their treating physicians, this study should help to relieve the anxiety that early treatment with levodopa will not induce a more rapid progression of the disease and may even improve the quality of life in the earliest stages.

PD MED Collaborative Group. Long-term effectiveness of dopamine agonists and monoamine oxidase B inhibitors compared with levodopa as initial treatment for Parkinson’s disease (PD MED): a large, open-label, pragmatic randomized trial. The Lancet, 2014; DOI: 10.1016/S0140-6736(14)60683-8


Review by Marcia McCall

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