Use of certain enzyme-blocking drugs found to decrease quality of life in patients with PD

Quality of life declined with use of certain enzyme-blocking drugs when measured against dopamine agonists in patients with Parkinson’s disease prescribed levodopa to correct motor issues, according to a study published in JAMA Neurology.

“Levodopa is the most commonly and effective initial treatment for Parkinson disease," Richard Gray, MSc, Nuffield Department of Population Health, University of Oxford, and colleagues wrote. "However, after prolonged or high-dose use, motor complications such as abnormal involuntary movements (dyskinesia) and motor fluctuations (premature decrease in the drug’s effects and unpredictable switching between on and off phases), can develop. Another drug class can then be added to reduce motor complications and levodopa dose.” 

“The most widely used adjuvant drugs are dopamine agonists and dopamine reuptake inhibitors, such as catechol-O-methyltransferase inhibitors and monoamine oxidase type B inhibitors,” they added. “Studies comparing brief treatment with these drugs vs. placebo among patients with motor complications have reported that each drug can improve motor function.”

Researchers sought to compare long-term effects on the quality of life of patients with PD when prescribing a dopamine agonist against a dopamine reuptake inhibitor (DRI) during levodopa therapy. The substances chosen were a monoamine oxidase type B (MAO-B) inhibitor and a catechol-O-methyltransferase (COMT) inhibitor.

The randomized clinical trial recruited 500 participants diagnosed with idiopathic PD who displayed uncontrolled motor issues, from 64 neurology and geriatric clinics across Europe, between Feb. 23, 2001, and Dec. 15, 2009. Most of these clinics were located in the U.K., along with one each in the Czech Republic and Russia. Data from the trial were analyzed between 2017 and 2020. Mean age of enrollees was 73 years old, and 62.8% of participants were male.

Patient outcomes were assessed before the study’s commencement, at the 6-month and 12-month marks after initial randomization, and then every year thereafter.

Results showed that, although examining a median range of 4.5 years of study follow-up, enrollees placed in the dopamine agonist group scored on average 2.4 points better than those placed in the combined MAO-B and COMT cohorts. Participants who were given MAO-B averaged 4.2 points higher than those assigned COMT group. When dopamine agonists were compared with MAO-B inhibitors only, outcomes for controlling progression of PD were similar, suggesting these agents may be underused as supplemental therapy.

“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,” Gray and colleagues wrote. “However, the use of either dopamine agonists or MAO-B inhibitors as initial adjuvant therapy appeared to be preferable to entacapone, which was the only COMT inhibitor assessed,” they said.

In an editorial by Tanya Simuni, MD, from the Parkinson's Disease and Movement Disorders Center, Northwestern University Feinberg School of Medicine, and Michael S. Okun, MD, from Norman Fixel Institute for Neurological Diseases, University of Florida Health, the pair praised the researchers for strong assessment of real-world experience by canvassing a large population and lengthy follow-up time frame from which to draw accurate and statistically meaningful conclusions.

However, Simuni and Okun pointed out that the rate of withdrawal from the drugs was as high as 50% at the 1-year and 5-year marks due to adverse effects such as psychosis and confusion. In addition, they noted that 73% of participants required some form of hospitalization during the study follow-up duration, with 50% of those due to falls, fractures and worsening motor function related to PD.

The doctors concluded that, although levodopa should remain the medical standard for PD treatment of uncontrolled motor issues, there appears to be little long-term benefit in any current adjunctive therapies, as examined above.