The End for Levodopa Phobia: New Study Shows Sinemet is a Safe Initial Therapy for Treatment of Parkinson’s Disease
You can find out more about NPF's National Medical Director, Dr. Michael S. Okun, by also visiting the NPF Center of Excellence, University of Florida Center for Movement Disorders & Neurorestoration. Dr. Okun is also the author of the Amazon #1 Parkinson's Best Seller 10 Secrets to a Happier Life.
In November 2011 we wrote about an important phenomenon called levodopa phobia, or avoidance of dopamine as a treatment for Parkinson’s disease. Many Parkinson’s disease patients and family members have been unnecessarily alarmed by the continuing reports that Sinemet and/or Madopar (European Sinemet) may accelerate disease progression, and that doses and drug intervals should be limited. These reports have unfortunately been fueled by sparse human evidence. Patients need to be aware that dopamine replacement therapies such as Sinemet and Madopar remain the single most effective, and single most important treatment for Parkinson’s disease worldwide. This month’s “What’s Hot” column will update the previous 2011 column, and focus on the new evidence published in the Lancet this month by the PD MED Collaborative Group.
Neurology previously published an article in 2011 citing that there was important evidence that dopamine replacement therapy is not toxic, and does not accelerate disease progression. Parkkinen and colleagues at Queen Square in London examined pathology in 96 post-mortem Parkinson’s disease brains, and paired the tissue with clinical information including levodopa use. The study concluded that in the human condition “chronic use of L-dopa does not enhance progression of Parkinson’s pathology.”
In an accompanying editorial, two prominent neurologists in the field pointed out that there “remains lingering concerns as to whether levodopa is toxic to dopamine neurons and accelerates the degenerative process.” The science quoted to support these claims has included levodopa undergoing auto-oxidation, and forming reactive oxygen species and toxic protofibrils. Additionally, the science includes a classical experiment that showed when levodopa was mixed with brain cells placed in a dish, there was toxicity. The research, however, has fallen short in demonstrating toxicity of the drug in the human form of Parkinson’s disease. There now exist broad levels of evidence from many studies across many countries (including most recently the ELLDOPA study) that levodopa is extremely beneficial to the human patient, and that levodopa has had a positive effect on disease course. Sinemet was recently reported as the most commonly administered drug among 7000+ patients being followed longitudinally in the National Parkinson Foundation Quality Improvement Initiative study. Expert practitioners who reported in this database utilized levodopa more than any other drug-- including dopamine agonists, and they used levodopa more (not less) as disease durations increased.
The newest study published in this month’s Lancet included newly diagnosed patients randomized to receive a dopamine agonist, a monoamine oxidase inhibitor (MAOBI) or levodopa. The primary outcome was the mobility dimension on the Parkinson’s disease questionnaire (PDQ-39) quality-of-life scale which is a validated way to measure meaningful improvements. There were 1620 patients randomized and followed. The three year follow-up revealed the PDQ-39 mobility scores were better in levodopa as compared to the other two groups. Follow-up at 7 years revealed levodopa was the best therapy, but there was a small difference favoring initial therapy with the MAOBI when this drug was compared to a dopamine agonist. The treatment related side effects were less in levodopa.
Over the past two decades the trendy phenomenon, referred to as levodopa phobia (intentionally avoiding prescriptions for levodopa) likely impeded the best clinical care for many Parkinson’s disease patients. An accompanying editorial to the recent Lancet article pointed out that levodopa phobia and also the favoring of agonist therapy was primarily driven by aggressive pharmaceutical marketing. The Lancet study revealed that all three therapies should be considered, but ultimately that the choice of drugs should be tailored to the individual patient. Patient-rated mobility in this study clearly favored initial levodopa therapy.
What all this adds up to for patients and for Parkinson’s sufferers is that Sinemet and Madopar should be considered safe and effective as initial treatments for Parkinson’s disease. The doses and intervals should be frequently adjusted by an experienced neurologist/practitioner in order to maximize benefits, and to tailor to individual symptoms. Patients and families should keep in perspective that the “talk” about levodopa being toxic and accelerating disease progression (levodopa phobia) can prove a major distractor to good care practices. Precious minutes in the doctor-patient relationship should not be wasted on these claims, and prescribers should not avoid or under-dose this critical therapy, especially in patients with treatable symptoms. Critics of Sinemet and Madopar will need to bring forward much stronger human data if they wish to change clinical practice. In the mean time, we need to serve our patients by sharing with them the weight of the evidence which strongly supports that levodopa replacement therapy is not toxic, does not accelerate Parkinson’s disease, and can be used safely as initial therapy.
Parkkinen L, O'Sullivan SS, Kuoppamäki M, Collins C, Kallis C, Holton JL, Williams DR, Revesz T, Lees AJ. Does levodopa accelerate the pathologic process in Parkinson disease brain? Neurology. 2011 Oct 11;77(15):1420-6. Epub 2011 Sep 14.
Olanow CW, Obeso JA. Levodopa toxicity and Parkinson disease: Still a need for equipoise. Neurology. 2011 Oct 11;77(15):1416-7. Epub 2011 Sep 14.
Fahn S. Parkinson disease, the effect of levodopa, and the ELLDOPA trial. Earlier vs Later L-DOPA. Arch Neurol. 1999 May;56(5):529-35.
Okun MS. An Important Update for Clinicians Treating Parkinson’s Disease Patients: Is This the End of Levodopa Phobia. New England Journal of Medicine Journal Watch, June, 2014.
Kurlan R. “Levodopa phobia”: A new iatrogenic cause of disability in Parkinson disease. Neurology 2005; 64: 923–24.
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 randomised trial. The Lancet - 11 June 2014 DOI: 10.1016/S0140-6736(14)60683-8.
Posted: 6/17/2014 8:00:48 AM by
Browse current and archived What's Hot in PD? articles, the National Parkinson Foundation's monthly blog for people with Parkinson's written by our National Medical Director, Dr. Michael S. Okun.
The End for Levodopa Phobia: New Study Shows Sinemet is a Safe Initial Therapy for Treatment of Parkinson's Disease
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Placing Stem Cells in Animal Models of Parkinson’s Disease: Another Important Step
Important News for the Parkinson’s Disease Community: More Evidence that Sinemet and Madopar are Not Toxic and do Not Accelerate Disease Progression
The Case for All Parkinson’s Disease Patients to be Co-managed by a Primary Care-Neurologist Team
Scientists say Research on Brain Proteins Involved in Parkinson’s Disease is “Shaping” Up
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How Will Group Visits for Parkinson’s Disease Fit into the Future of Parkinson’s Disease Care?
Why Patients Should be Wary of Chelation Therapy for Parkinson’s Disease
Opening the Door to Gene Therapy in Parkinson’s Disease: The Need for Refinement of the Technology and Approach
Does it Matter if I Can’t Get Brand Sinemet?
Should I get a DaTscan or PET scan to confirm my diagnosis of Parkinson’s disease?
A Critical Reappraisal of the Worst Drugs in Parkinson’s Disease
Environmental Risks for PD: Manganese, Welding, Mining, and Parkinsonism
Calling for the FDA to Revise the Eight Sinemet a Day Rule
Dry Cleaning Solvents and Potential Environmental Risks for Developing Parkinson’s Disease
Maintaining the Balance: Why Parkinson’s Disease Patients Need to Understand Drug Recalls, Withdrawals, and Safety Alerts
Shining a Light on Parkinson’s Disease: Optogenetics Has a Bright Future in Research
Poor Medication Management of Parkinson's Disease During Hospital Admissions: Patients and Families Can Improve Their Hospital-Based Management
Why Are Patches and Continuous Release Technology a Big Deal to Parkinson's?
Is the PD SURG Trial Another Surge Forward for DBS Therapy?
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New iPS Stem Cells for PD: What Does it Mean?
Time for Comprehensive Care Networks for PD
Is Parkinson's Disease a Prion Disease?
Parkinson's Disease Linked to Gaucher's Disease
Brain Cells Keep Time Stamps: Implications for Parkinson's Disease Therapies
Is it Safe to Have an MRI with a DBS in Place?
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Is it Time to Start Paying Attention to Pain Symptoms in Parkinson's Disease Patients?
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Keeping an Eye on Trials Important to the Parkinson's Disease Patient
Increased Risk of Melanoma in Parkinson's Disease
Finally a DBS Expert Consensus Statement Aimed at Their True Customers: The Patients
Pesticides and Environmental Exposure in Parkinson's disease: Should We Stay Away From the Stink Truck?
Is Exercise Effective Treatment and Protection Against PD?
Why are Transplant Trials Struggling to Succeed in the Treatment of PD?
Are Monoamine Oxidase Inhibitors Disease Modifying or Neuroprotective in PD?
Update on Gene Therapy for Parkinson's Disease