Dopamine antagonists and dopamine reuptake inhibitors (DRIs) seem to be equally effective in Parkinson’s disease (PD) and motor fluctuations uncontrolled by levodopa. Certain DRIs are more effective than others.
In the course of a “pragmatic, real-life clinical study,” the mean mobility score on the 39-item Parkinson’s Disease Questionnaire (PDQ-39) was 2.4 points higher for patients who received an adjuvant dopamine agonist vs those who received a DRI. The difference was not statistically significant.
Mobility scores were better for participants receiving monoamine oxidase type B (MAO-B) inhibitors than for those receiving catechol-O-methyltransferase (COMT) inhibitors.
“To many people’s shock the addition of an MAOB inhibitor was at least as effective as the addition of one of these more expensive dopamine-agonists” Richard Gray, DPhil the lead investigator, told Medscape Medical News.
“Although the differences aren’t huge they favor the most expensive drugs; so it makes sense to use these,” Gray said.
The results were published online the 28th of December in JAMA Neurology.
Head-to-Head Comparative Study
Dyskinesias, motor disturbances, and other signs can appear in patients with PD even when they are treated with levodopa. At this point in the progression of the disease, adjuvant therapy with dopamine antagonists or DRIs that include MAO-B inhibitors as well as COMT can alleviate these symptoms.
But, to date, there was no research linking these two drug classes or the effectiveness of MAO-B and COMT inhibitors.
The study, PD MED, involved 500 patients suffering from idiopathic PD with motor issues that could not be controlled by levodopa therapy. They required the addition of a different drug.
Gray said there were no studies comparing the main drugs prior to PD the MED.
Patients were randomly assigned, in groups of equal size and size, to receive a dopamine agonist an COMT inhibitor or an MAO-B inhibitor. Clinicians could select the drug from the assigned class they deemed appropriate.
Because of the length of the trial and the need to adjust dosages, the study groups were not blinded.
Functional status was the primary outcome of the study, measured using the mobility domain of PDQ-39. Other outcomes included other domains of the PDQ 39, the total PDQ39 score, and the degree of adherence to treatment. Before randomization, patients and caregivers were required to submit reports at six months, one year, and every year thereafter.
The population’s mean age was 73 years, and 62.8 percent were males. The baseline characteristics of patients were the same across treatment groups.
Ropinirole (43.2%) and pramipexole (35.0 percent) were the most frequently used agents for patients assigned to dopamine agonists. Common MAO-B inhibitors were oral selegiline (51.6%) and rasagiline (29.5%) respectively. Sublingual selegiline (13.8 percent) was also common. The majority (90.8 percent) of patients who were assigned to a COMT inhibitor received Entacapone.
Mobility Differences
After one year the discontinuation rates for dopamine agonists (30%) MAO–B inhibitors (38 percent), COMT inhibitors (36%) were comparable. The discontinuation rates for 5 years were also similar.
Treatment adherence was not affected by years, but adverse events were the primary reason for stopping all classes of drugs.
In a follow-up period of 4.5 years, PDQ39 mobility scores were 2.4 times higher in the dopamine agonist than in the MAO-B or COMT inhibitor groups, but this was not statistically significant. The researchers found no significant differences between the two groups on other tests.
The PDQ-39 mobility score was 4.2 points higher in MAO-B as compared to COMT inhibitors ( P =.03). The MAO-B inhibitor group also had higher scores in activities of daily living (4 points, P = .03) and emotional well-being (4.4 points, P = .009), and social support (3.7 points, P = .01).
Rate of dementia onset was lower in the MAO-B inhibitors group (32%) than in the COMT inhibitor group (37%) and mortality (55% vs 63 percent in the COMT inhibitor group, respectively). However, neither of the differences was statistically significant.
As evidenced by the patient reports, mobility and quality of life were significantly improved when a dopamine antagonist or MAO-B inhibitor was added.
Gray observed that the PD MED study included typical patients who received treatment in the same way as they would receive in a real-world clinical setting. The results were statistically reliable because of the large patient population.
Gray said that the results are reliable and can be applied to routine practice.
Strengths, Limitations
Commenting on the study for Medscape Medical News: Peter Hedera MD, PhD, Raymond Lee Lebby Endowed chair of Parkinson’s Disease Research, and director of The University of Louisville’s Movement Disorders Program, stated that there are only a handful of head-to-head drug trials.
Hedera, who was not involved in the research, claimed that the limitations placed on the practice of the study doctors, which were essential for the comparison of the different classes of drugs, led to an artificiality to the study.
“Very often, you’ll use a combination of COMT and MAO-B inhibition together,” he noted.
The advantage of MAO-B inhibitors lies in their greater impact on nonmotor symptoms than with COMT inhibitors, he said. “It’s almost unfair to compare them, because the pharmacology is much more complicated for MAO-B inhibition,” said Hedera.
This difference could partially explain the apparent superiority of MAO-B inhibitors over COMT inhibitors.
“It’s still a worthwhile study, and an extremely useful study that demonstrates the relative importance of these types of medications as adjuvant therapies,” said Hedera.
Levodopa remains the primary ingredient in PD treatment However, there are limits regarding its maximum dose, he added.
“We shouldn’t hesitate to use adjuvant therapy when it is needed in the event that motor control is not being achieved,” Hedera concluded.
The study was funded by the UK National Institute for Health Research (NIHR), UK Department of Health and Social Care (UK Department of Health and Social Care) and Parkinson’s UK. Gray was granted grants by the UK NIHR Health Technology Assessment Program during the course of the study. Hedera has reported no financial relationships with the study.
JAMA Neurology. Published online December 28 2021. Abstract.
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