A study published online in the Archives of Neurology involving two common drugs used to treat early-stage Parkinson's disease shows that, while the drugs each have advantages and disadvantages, the overall impact tends to even out over a long period of treatment.
"Clinicians and patients often struggle with what is the right initial approach to treating Parkinson's disease," said University of Rochester Medical Center neurologist Kevin Biglan, M.D., M.P.H., the lead author of the paper and a member of the Parkinson's Study Group, an international network of researchers that oversaw the clinical trial. "This study tells us that, over the long haul, patients on the different drugs end up at roughly the same place in terms of their level of disability and quality of life."
Parkinson's disease is a progressive neurological disorder that erodes a person's control over their movements and speech. Over time, Parkinson's patients may experience stiffness or rigidity of the arms and legs, slowness or lack of movement, and walking difficulties, in addition to tremors in their hands, arms, legs, jaw or face.
The study compared two drugs – levodopa and pramipexole – that are generally employed as the first line of treatment for Parkinson's disease. The two drugs use different mechanisms to counteract the decline in the production of dopamine in the brain that is a result of a progressive loss of cells that secrete the neurochemical. Levodopa is an amino acid that the body metabolizes into dopamine. Pramipexole is a dopamine agonist that binds with dopamine receptors on cells in the brain and mimics the chemical's molecular function.
While levodopa is considered to be better at addressing the motor control symptoms of the disease such as mobility issues and tremors, it is also associated with side effects such as dyskinesia (involuntary movements) and the effectiveness of the drug can diminish, or wear off, over time. Pramipexole is less effective with respect to motor control symptoms and more often causes sleepiness, but is less commonly associated with dyskinesias and wearing off. Pramipexole is often prescribed because clinicians believe it essentially extends the window in which the patient can benefit from levodopa by delaying the initial use of the drug – and its eventually wearing off. Most Parkinson's patients end up taking levodopa at some point regardless of their initial treatment because it is more effective at improving the symptoms of the disease.
The initial study followed 301 Parkinson's patients in 22 sites in the U.S. and Canada over a 2 year period. A sub-set (222) of the group was followed for an additional 4 years. Half the patients were randomly assigned to be initially treated with levodopa and the other half with pramipexole. After 6 years of follow-up, essentially all of the participants (90%) were taking levodopa. The researchers evaluated study participants using tools that measure disability (ability to perform daily activities), side effects, disease severity, and the patient's sleepiness.
The study confirmed that patients who are initially treated with levodopa are more likely to develop motor complications such as dyskinesias and wearing off even 6 years after treatment. However, it also shows that these complications did not have a significant impact on the quality of life or disability of the patients.
"Clinicians and patients still need to establish their treatment priorities to understand unique circumstances that argue in favor of one drug vs. the other," said Biglan. "However, this study should assuage any concerns that the treatment decisions that are made early in the disease will have long-term implications, which does not appear to be the case."
The study was conducted by the Parkinson's Study Group CALM (Comparison of the Agonist Pramipexole with Levodopa on Motor Complications) Cohort and funded by Pharmacia Corp. and Boehringer Ingelheim.
- Parkinson Study Group CALM Cohort Investigators. Long-term Effect of Initiating Pramipexole vs Levodopa in Early Parkinson Disease. Archives of Neurology, DOI: 10.1001/archneurol.2009.32
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