No difference in disease progression was found whether levodopa, the most commonly prescribed drug to control symptoms in Parkinson's disease, was initiated at the time of diagnosis or delayed, according to a study published online in the New England Journal of Medicine on January 24.
Recently, doctors and researchers have been concerned that early use of levodopa could accelerate disease progression or increase long-term complications, such as involuntary movements (dyskinesia) and fluctuations of motor control, as well as the wearing-off of the drug's effect or a delay in its effect.
In 2004, a clinical trial called Earlier versus Later Levodopa Therapy in Parkinson Disease (ELLDOPA), studied levodopa's effect on the rate of progression and speculated that the drug either slowed progression or potentially delayed the appearance of symptoms.
Brain imaging data also revealed that levodopa either accelerates the death of dopamine-producing neurons or renders the protein responsible for transporting dopamine to brain nerve cells less effective by slowing down dopamine production. These results were inconclusive in determining whether levodopa affects the progression of Parkinson's disease beyond helping to control motor symptoms.
To find out if giving levodopa to early-stage Parkinson's disease patients is safe, and whether it slows or accelerates progression, researchers from Amsterdam University Medical Centers in the Netherlands recruited 445 patients with early Parkinson's disease. The patients were randomized to receive either 100 mg of levodopa three times a day in combination with 25 mg carbidopa three times a day for 80 weeks (early-start group) or placebo for 40 weeks followed by levodopa/carbidopa for 40 weeks (delayed-start group) from 2011 to 2016.
The team used the Unified Parkinson's Disease Rating Scale (UPDRS), which measures disease progression, and includes subscales of mental function, activities of daily living, and motor function. The UPDRS score ranges from 0 to 176, with higher scores signifying more severe disease. The researchers calculated scores at baseline and at week 80 to quantify the difference between the early-start group and the delayed-start group.
At baseline, the average UPDRS score was 28.1 points in the early-start group and 29.3 points in the delayed-start group. From baseline to week 80, the change in UPDRS scores was −1.0 point in the early-start group and −2.0 points in the delayed-start group.
During the first 40 weeks, nausea was more common among patients in the early-start group than those in the delayed-start group (23 percent versus 14.3 percent). At 80 weeks, the rates of dyskinesia and levodopa-related fluctuations in motor response did not differ significantly between the two groups. The researchers concluded patients in the early-start group were not negatively impacted by their prolonged exposure to the drug.
"[L]evodopa at a dose of 100 mg three times per day in combination with carbidopa at a dose of 25 mg three times per day had no disease-modifying effect, either beneficial or detrimental, on early Parkinson’s disease among patients who were evaluated over the course of 80 weeks," the researchers wrote.
The researchers call for more randomized clinical trial calls to evaluate whether higher doses of the drug, longer periods of administration, or the initiation of levodopa at later stages of the disease could influence its course.
