Patients in Need of Levodopa Add-on Rate 3 Treatment Classes in Trial

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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In treating Parkinson’s symptoms that aren’t being adequately controlled by levodopa, monoamine oxidase type B (MAO-B) inhibitors are better than catechol-O-methyltransferase (COMT) inhibitors, according to patient-reported assessments in a clinical trial.

The real-world study found no difference in effectiveness between MAO-B — like COMT, a dopamine reuptake inhibitor — and dopamine agonists as an add-on therapy.

Results were published in the study, “Long-term Effectiveness of Adjuvant Treatment With Catechol-O-Methyltransferase or Monoamine Oxidase B Inhibitors Compared With Dopamine Agonists Among Patients With Parkinson Disease Uncontrolled by Levodopa Therapy,” in JAMA Neurology.

Parkinson’s disease is caused by the death or dysfunction of dopamine-producing nerve cells in the brain. Levodopa and its derivatives, which basically work by giving the brain more raw materials with which to make dopamine, are a standard treatment.

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When levodopa alone is not enough to control Parkinson’s symptoms, several kinds of adjuvant, or add-on, treatments can be given to help control motor symptoms.

One class of adjuvant treatment is called dopamine agonists, which effectively work by mimicking the activity of dopamine. Another class is dopamine reuptake inhibitors or DRIs, which increase the amount of dopamine available to nerve cells sending signals by blocking its absorption by cells. MAO-B inhibitors and COMT inhibitors both are sub-classes of DRI.

All of these medications have been shown in clinical trials to be more effective than a placebo at easing Parkinson’s symptoms. But no trials have directly compared these medications, making it impossible to draw firm conclusions about whether one class or another generally is better.

The Parkinson Disease Medication (PD MED) trial (ISRCTN69812316) recruited 500 people with idiopathic (of unknown cause) disease at 64 clinics — one in Russia, one in the Czech Republic, and the rest in the U.K. It enrolled 314 men and 186 women with a mean age of 73. All had symptoms that were not being controlled with levodopa alone, and none had dementia.

Participants were randomly assigned to treatment with a dopamine agonist, a MAO-B inhibitor, or a COMT inhibitor; each patient’s doctor decided which specific medication in each class to prescribe.

The trial’s main goal was to evaluate the effect of treatment on participants’ functional status, as assessed by the mobility domain of the 39-item Parkinson’s Disease Questionnaire (PDQ-39), a patient-reported measure of life quality. PDQ-39 scores were assessed before starting with the add-on treatment, after six months, and then annually for up to five years.

Over its course, rates of discontinuation were similar among the three treatment groups — about a third of participants had stopped with the medication by one year, and just over half by five years. Across treatments, older patients were more likely to discontinue therapy.

Adverse events (side effects) was the most common reason for discontinuing treatment, particularly psychiatric problems (e.g., psychosis or confusion) for patients on dopamine agonists or MAO-B inhibitors, and digestive problems for those on COMT inhibitors.

With a median follow-up of 4.5 years, average mobility scores on the PDQ-39 did not differ significantly between patients given dopamine agonists or DRIs (MAO-B or COMT inhibitors, assessed collectively). There also were no significant differences in rates of death or dementia.

However, significant differences were evident between those given MAO-B and COMT inhibitors. Specifically, average PDQ-39 mobility scores were 4.2 points better with MAO-B inhibitors at the end of follow-up. Other PDQ-39 sub-scores — including activities of daily living, emotional well-being, and social support — also were significantly better with MAO-B inhibitors compared to COMT inhibitors.

Patients treated with MAO-B were generally less likely than those given COMT inhibitors to develop dementia, spend time in the hospital, or die; however, none of these differences reached statistical significance meaning they could be due to chance.

Other analyses generally showed no difference in PDQ-39 mobility scores between patients given dopamine agonists and those on MAO-B inhibitors. By contrast, dopamine agonists tended to yield better results than treatment with COMT inhibitors — possibly owing to the relatively lower number of patients given dopamine agonists in the trial, however, this difference was not statistically significant.

Scores on the EuroQol 5-dimension 3-level, a measure of treatment cost-effectiveness, generally followed a similar trend to PDQ-39 scores. The researchers are planning to publish a separate study with full cost analyses.

“In this randomized clinical trial, no measurable improvement in patient-rated quality of life was observed between patients receiving dopamine agonists compared with DRIs, either MAO-B or COMT inhibitors, as adjuvant therapy for the treatment of later-stage PD [Parkinson’s disease]. However, the use of either dopamine agonists or MAO-B inhibitors as initial adjuvant therapy appeared to be preferable to” COMT inhibitors, the researchers concluded.

These results suggest that “MAO-B inhibitors might be underused as adjuvant therapy for the treatment of people with PD,” they added, noting these DRIs are “less expensive” than dopamine agonists or COMT inhibitors.