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.
Many Parkinson’s disease patients and families 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 focus on the evidence including the most recent paper on this important topic.
In this month’s issue of Neurology, important evidence is presented 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. In fact, there now exists broad levels 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 4000+ 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.
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 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 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, and does not accelerate Parkinson’s disease.
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.
Warren Olanow C, 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.
Posted: 11/2/2011 9:06:02 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.
Pimavanserin and the Hope for a Better Drug for Hallucinations and Psychosis in Parkinson’s Disease
Halting of the Creatine Study
The Importance of Identifying and Treating Caregiver Strain
Putting Parkinson’s Disease Information into the Palm of Your Hand: Parkinson’s Enters the Smartphon
What Parkinson’s Disease Patients Need to Know about H. Pylori Gastrointestinal Infections
A2A Receptor Antagonists and Parkinson’s Disease Treatment
Another Setback for Trophic Factor Treatment in Parkinson's Disease
IPX066 and What Patients Really Want in New Carbidopa/Levodopa (Sinemet) Formulations
The Weather Forecast for Parkinson’s Disease Calls for Worldwide Economic Storm
Defeating the Barriers to Implementing Exercise Regimens in Parkinson’s Disease Patients
When should you start medication therapy for Parkinson’s disease?
Neurologist Care Reduces Hospitalizations in Parkinson's Disease
A Victory in Court for Parkinson's Disease Patients who Require Ongoing Rehabilitative Therapies
Given the recent FDA announcement about Mirapex (pramipexole), should I be worried about dopamine agonists?
What about the new Parkinson’s Disease Vaccine? What should I know?
Caffeine as a Potential Treatment for Parkinson’s Disease
Time to Consider GPi DBS for Parkinson’s Disease: A Shift in the Practice of Patient Selection for DBS
A New Treatment for Parkinson’s Disease-Related Constipation
Too Many Pills: Improving Delivery Systems for Parkinson’s Disease Drugs
Measuring Quality and Assessing Depression in Parkinson's Disease
Watch out for Unexpected Obstacles if You Use a Cueing Strategy to Break Freezing of Gait in Parkinson’s Disease
Pill Color, Generic Medications and Insurance Issues: Important Medication-Related Tips for the Parkinson’s Disease Patient
Are Blood Tests for Parkinson’s Disease on the Horizon?
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
Who Actually Takes Care of Most of the Parkinson’s Patients Worldwide: The Need for Education and the Parkinson’s Toolkit
If you are Dizzy or Passing Out, it could be Your Parkinson’s Disease or Parkinson’s Disease Medications
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?
Cycling in PD in Those Who Can’t Walk: Is it Possible?
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?
Take Care of Your Bones as They Are Affected in Parkinson's Disease (Even in Men)
Is it Time to Start Paying Attention to Pain Symptoms in Parkinson's Disease Patients?
Glutathione Fails to Demonstrate Significant Improvement in PD Symptoms
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