The End of Levodopa Phobia?

Summary and Comment |
June 20, 2014

The End of Levodopa Phobia?

  1. Michael S. Okun, MD

An important update for clinicians treating patients with Parkinson disease

  1. Michael S. Okun, MD

Which medication should be used as first-line therapy for Parkinson disease (PD) has been an open and important question. To address this question, researchers conducted a pragmatic, open-label, randomized trial in patients with a new diagnosis of PD. The 1620 patients were randomized to receive a dopamine agonist (632 patients), a monoamine oxidase inhibitor (MAOBI; 460 patients), or levodopa (528 patients). Both patients and clinicians were aware of their treatment status. The primary outcome was the mobility dimension on the Parkinson's disease questionnaire (PDQ-39) quality-of-life scale.

Median follow-up was 3 years. The average PDQ-39 mobility score over the first 7 years was 1.8 points better with levodopa than with the other two treatments, a significant difference. At 7 years, levodopa remained the best therapy, but there was a small difference favoring initial therapy with an MAOBI versus a dopamine agonist. A generic quality-of-life measure confirmed the study's major finding favoring levodopa therapy. Rates of dementia, admission to care institutions, and death were not significantly different among groups; however, the study was not designed to assess these outcomes. There were important differences in rates of discontinuation due to treatment-related side effects (28% with dopamine agonists, 23% with MAOBIs, 2% with levodopa).


These results will likely affect the clinical care of the PD patient, especially in the coming years. Over the past two decades, a trendy phenomenon referred to as levodopa phobia (intentionally avoiding prescriptions for levodopa) has affected both prescribing physicians and patients, largely in a negative way (Neurology 2005; 64:923). As editorialists note, this change in clinical practice was associated with aggressive pharmaceutical marketing. These new results suggest that all therapies have potentially beneficial effects in PD and that initiating early levodopa therapy can have short- and long-term benefits, as well as a tolerability advantage. The study did not adequately address whether patients younger than 70 would be more appropriate for levodopa-sparing strategies than older patients; this point should be explored in future studies. All three therapies should be considered and the choice of drugs should be tailored to the individual patient, although patient-rated mobility favors levodopa therapy, as does the risk for impulse control issues and other side effects.

Editor Disclosures at Time of Publication

  • Disclosures for Michael S. Okun, MD at time of publication Grant / Research support NIH; National Parkinson Foundation; Michael J. Fox Foundation; Tourette Syndrome Association; Bachmann-Strauss; Dystonia Medical Research Foundation Editorial boards National Parkinson Foundation; Parkinsonism and Related Disorders; Tremor and Hyperkinetic Disorders Leadership positions in professional societies National Parkinson Foundation (National Medical Director); Tourette Syndrome Association (Co-Chair Medical Advisory Board); The International Parkinson and Movement Disorder Society (International Executive Committee)


Reader Comments (2)

Anne Selig PharmD Other Healthcare Professional, Pharmacology/Pharmacy, Steward Health

I agree with the difference in side effect profile, impressive for levodopa. I hope this does change current practice. Too long for early onset PD patients to wait with poor quality of life for levodopa.

JOACHIM ZEEH Physician, Geriatrics, Meiningen, Germany; Geriatric Hospital

A reassuring study. Among many Geriatricians, LDOPA used to be the first choice treatment, even during the years of agonist hype. Impressive from my point of view are the tremendous differences between the three drug classes in terms of side effect associated treatment discontinuation.

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