Levodopa-Sparing Medications May Help Patients in Early Stages of Parkinson’s, Study Suggests

Neurologists treating patients with early-stage Parkinson’s disease should prescribe more often therapies that spare patients from starting levodopa too soon in order to delay onset of side effects associated with long-term use of the medicine, findings from a study conducted in Romania suggest.

Researchers believe that even if a doctor believes a patient’s clinical situation required management with levodopa, they should first try to combine it with other antiparkinsonian therapies — such as dopamine agonists or monoamine oxidase B inhibitors — in order to allow lower levodopa doses.

These findings resulted from a study, “Therapeutic strategies in the early stages of Parkinson’s disease: a cross-sectional evaluation of 15 years’ experience with a large cohort of Romanian patients,” which was published in the journal Neuropsychiatric Disease and Treatment.

Currently, the most effective and cost-saving therapy for lessening Parkinson’s symptoms is substitution therapy with levodopa. However, a major drawback of this therapy is the side effects associated with its long-term use.

After four to six years of treatment with levodopa, many patients may start experiencing spontaneous involuntary movements (dyskinesia), with some patients also having impulsive and compulsive behaviors. Its effectiveness can also reduce over time, causing patients to experience wearing-off effects, meaning that the therapy loses its ability to effectively manage Parkinson’s symptoms before it is time for the next dose.

Some clinical evidence seems to indicate that in many cases “if the therapy is started too early and with high doses, these complications may appear earlier and can be more severe, especially in younger patients,” the researchers wrote. This leads clinicians to try to avoid these side effects and adverse reactions by limiting levodopa doses as much as possible.

Based on clinical efficacy data from newer antiparkinsonian therapies in younger patients (under 60 years), European guidelines propose the use of levodopa-sparing medications as a first option for early-stage patients to delay the onset of motor and non-motor complications. But there is little real-world data to confirm how these therapeutic recommendations are being applied in clinical practice.

Therefore, the researchers reviewed the medical records of patients with early-stage Parkinson’s hospitalized between 2003 and 2017 at Târgu Mures Emergency County Hospital, in Romania, to gather real-world data on the use of levodopa and alternative therapies.

During this 15-year period, a total of 2,379 patients with Parkinson’s were hospitalized, of whom 1,237 had received the diagnosis for five years or less. The researchers justified this time window because most practicing neurologists consider that the efficacy of levodopa-sparing treatment strategies is significantly reduced after a five-year period. Only patients with early-stage disease were included in the study.

In this group, 18 patients (1.5%) were receiving monoamine oxidase-B inhibitors (MAO-Bi). A total of 665 patients were taking dopamine agonists, of whom 120 were taking the therapy alone (9.7%) and  83 patients (6.7%) in combination with MAO-Bi. Many of the patients (42%) were only taking levodopa, while 481 patients (38.8%) were taking levodopa in combination with other antiparkinsonian therapies.

Assessment of levodopa daily doses, either alone or in combination with other therapies, did not reveal any significant differences between patients grouped by age (younger than 50, 50–65, or older than 65).

“The therapeutic strategies used in the early stages of Parkinson’s disease in the study period are similar to those found in the literature,” the researchers wrote. Still, they recommend that “neurologists treating this disease should, with due diligence, apply a greater proportion of different levodopa-sparing combinations, especially if they are not financially burdensome.”

What makes clinicians decide to prescribe levodopa or other dopamine agonists in the first place is difficult to access through this study, and can be influenced by a number of factors, the researchers said.

“Because our study looks at a long period it is hard to retrospectively assess how much of the clinical decisions was influenced by the early optimism (as reflected in the initial studies) regarding the potential disease-modifying effect as well as the magnitude of the clinical efficacy of dopamine agonists,” they added.

Still, “if the severity of the clinical image requires substitution therapy, the use of combined therapies can significantly reduce levodopa doses and thus the requirement to use the minimum efficient levodopa dose can be achieved,” they concluded.