Levodopa Is as Effective as Newer Drugs for the Initial Treatment of Parkinson's Disease

S. Andrew Josephson, M.D.


AccessMedicine from McGraw-Hill 

Patients with idiopathic Parkinson’s disease (PD) are treated, often successfully, with various medications in the hope of preventing progressive disability. Three major classes of drugs are used by clinicians for initial PD therapy: levodopa, dopamine agonists, and monoamine oxidase type B inhibitors (MAOBIs). Levodopa is the oldest class of these medications, but it is thought to be associated with a higher incidence of long-term motor complications; therefore non-levodopa classes of medications are often used preferentially, especially in younger patients. In an important trial, the PD MED Collaborative Group (2014) aimed to determine which of these strategies is most effective in patients with PD.

The authors conducted an open-label, randomized trial in patients with a new diagnosis of PD made by a movement disorder specialist in multiple centers mainly in the United Kingdom. All patients either were previously untreated or had been treated for <6 months with uncertainty as to which therapy to begin. Patients were randomly assigned to levodopa, dopamine agonists, or MAOBIs. Both patients and their physicians were aware of the treatment allocation. The two primary outcomes examined were scores on the mobility subscale of the Parkinson’s disease questionnaire (PDQ-39) and a measure of quality-adjusted life-years using the EuroQol EQ-5D scale.

A total of 1620 patients were enrolled in the study, and those assigned to treatments other than levodopa were given a variety of specific agents in each class at their physician’s discretion. Median follow-up was 3 years. By the end of the study, drug discontinuation had occurred in 28% of patients assigned to dopamine agonists, 23% of those taking MAOBIs, and 2% of patients assigned to levodopa (p < .0001). The PDQ-39 mobility scores averaged 1.8 points better [95% confidence interval (CI), 0.5–3.0; p = .005] in those assigned to levodopa compared with those assigned to the other classes of medications, and there was no evidence of this effect changing over 7 years of observation. EQ-5D scores were found to be 0.03 points better (95% CI, 0.01–0.05; p = .0002) in those assigned to levodopa compared with those assigned to the other agents. There were no differences in these results when stratified by age.

Secondary outcomes examined, including rates of institutionalization, development of dementia, and decline in Mini-Mental State Examination (MMSE) scores, and death, were not significantly different among the treatment groups. While patients in the levodopa group were significantly more likely to develop dyskinesias than those in the other groups, there was no significant difference found in rates of motor fluctuations.

This important trial demonstrates that there is no clear disadvantage to using levodopa as initial therapy for PD compared with newer (and usually more expensive) classes of medication. While the significant differences in favor of levodopa found here are modest, they certainly argue against the drug being a worse choice for initial treatment. The open-label design of the study is a limitation, but, as the authors point out, any bias would generally be expected in the direction of the commonly held belief that non-levodopa therapies would be superior. For now, clinicians should counsel their patients with newly diagnosed PD that levodopa is a reasonable choice for first-line therapy, and the risks and benefits of each medication choice should be discussed with these results in mind.