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Orally Disintegrating Selegiline Allows Parkinson's Disease Patients to Lower Dopamine Agonist Dose

  • Authors: News Author: Kathleen Louden
    CME Author: Désirée Lie, MD, MSEd
  • CME Released: 6/27/2008
  • Valid for credit through: 6/27/2009
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Target Audience and Goal Statement

This article is intended for clinicians who want to maintain a current understanding of recent research and evidence in the treatment of Parkinson's disease.

The goal of this activity is to provide medical news to primary care clinicians and other healthcare professionals in order to enhance patient care.

Upon completion of this activity, participants will be able to:

  1. Inform clinicians of the latest medical information on the treatment of Parkinson's disease as presented at the 12th International Congress of Parkinson's Disease and Movement Disorders.
  2. Describe the relevance of the findings on the use of orally disintegrating selegiline to reduce adverse effects of treatment to clinicians in the care of their patients with Parkinson's disease who are receiving levodopa, pramipexole, or ropinirole.


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  • Kathleen Louden

    Kathleen Louden is a freelance writer for Medscape.


    Disclosure: Kathleen Louden has disclosed no relevant financial relationships.


  • Brande Nicole Martin

    Brande Nicole Martin is the News CME editor for Medscape Medical News.


    Disclosure: Brande Nicole Martin has disclosed no relevant financial information.

CME Author(s)

  • Désirée Lie, MD, MSEd

    Clinical Professor, Family Medicine, University of California, Orange; Director, Division of Faculty Development, UCI Medical Center, Orange, California


    Disclosure: Désirée Lie, MD, MSEd, has disclosed no relevant financial relationships.

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Orally Disintegrating Selegiline Allows Parkinson's Disease Patients to Lower Dopamine Agonist Dose

Authors: News Author: Kathleen Louden CME Author: Désirée Lie, MD, MSEdFaculty and Disclosures

CME Released: 6/27/2008

Valid for credit through: 6/27/2009


From 12th International Congress of Parkinson's Disease and Movement Disorders

June 27, 2008 (Chicago, Illinois) — Patients with Parkinson's disease (PD) can reduce the dose of dopamine agonist therapy — and thus the common adverse effects — without decreasing motor function, by taking daily the orally disintegrating form of selegiline (Zelapar), a new study shows.

With 12-week adjunctive therapy using this monoamine oxidase type B inhibitor, the adverse effects of daytime sleepiness, hallucinations, pedal edema, and impulsive behaviors resolved or improved in most patients, despite greatly lowering or discontinuing the dose of the dopamine agonist, the authors reported.

The phase 4, open-label, multicenter A to Z Study was conducted to learn if adding selegiline orally disintegrating tablets, while reducing or eliminating the dose of a dopamine agonist that is causing one of these adverse effects, can eliminate the adverse effect and maintain control of PD symptoms.

The study's principal investigator, Rajesh Pahwa, MD, told Medscape Neurology & Neurosurgery, "There was some concern that we would lose efficacy [after reducing the dopamine agonist dose], but we did not."

Dr. Pahwa, professor of neurology and director, Parkinson's Disease and Movement Disorder Center, University of Kansas Medical Center, Kansas City, presented the preliminary data here at the 12th International Congress of Parkinson's Disease and Movement Disorders.

Adverse Events Reduced

The study included 50 PD patients (23 men and 27 women) who were receiving levodopa and either pramipexole or ropinirole and who reported experiencing at least 1 of the 4 adverse events commonly related to dopaminergic therapy. Some patients had more than 1 adverse event. Adverse events were measured by patients' self-report and the Epworth Sleepiness Scale, Neuropsychiatric Inventory, Barratt Impulsiveness Scale, and ankle circumference. Control of PD symptoms was measured by the Unified Parkinson's Disease Rating Scale (UPDRS).

At baseline, 41 patients had daytime sleepiness, defined as a score greater than 10 on the Epworth scale. Twenty-three patients had impulsive behaviors, including compulsive gambling, sexual urges, eating, and buying, which were not severe enough to require immediate attention. Bothersome ankle swelling was present in 22 patients, and hallucinations, in 14.

The dopamine agonist dose was reduced by half at baseline, and 1.25 mg/day of orally disintegrating selegiline was added to the regimen, according to the abstract. At 6 weeks, selegiline was increased to 2.5 mg/day. If the patient's adverse events remained bothersome and efficacy was unchanged, the agonist dose was further reduced at weeks 3 and 6. The final mean daily doses at 12 weeks were 0.5 mg of pramipexole and 3 mg of ropinirole.

Some patients discontinued dopaminergic therapy (data not available), but, if Parkinson's symptoms returned, they could return to a combination of the 2 drug classes, said coauthor Kelly Lyons, PhD, research associate professor of neurology, University of Kansas Medical Center.

According to patients' self-reporting at week 12, hallucinations disappeared in 57% or improved in 36%; daytime sleepiness was resolved in 22% or was reduced in 68% of patients; impulsive behavior in 35% and 48%; and pedal edema in 23% and 46%, respectively. Results of objective testing, such as the UPDRS, matched self-reports, Dr. Lyons said in an interview.

No Loss of Efficacy

At the end of the study, 17 (34%) of the patients reported that they preferred treatment with orally disintegrating selegiline alone and no dopamine agonist, and 31 (62%) preferred a combination of reduced-dose dopamine agonist and selegiline. Only 2 patients (4%) preferred the agonist alone, study data shows.

At week 12, there was no statistically significant loss of efficacy of medical therapy, Dr. Pahwa said. Motor scores on the UPDRS actually improved slightly to a mean of 20.9 from a baseline of 22.6.

"A drug like Zelapar has fewer adverse events than dopamine agonists but similar efficacy," Dr. Pahwa said in an interview.

Study Limitations

One conference attendee, who did not participate in the study, said that doses of dopamine agonists appeared to be reduced to "subtherapeutic" levels. Carl Clarke, MD, FRCP, professor of clinical neurology at the University of Birmingham in the United Kingdom, told Medscape Neurology & Neurosurgery, "The authors may as well have taken the patients off the dopamine agonists altogether."

Although the study showed no significant effect on motor function of lowering the agonist dose, Dr. Clarke said, "There are only 50 patients in the study, so it's probably underpowered to look at motor function."

Currently, he usually prescribes a catechol-O-methyltransferase inhibitor when his patients with PD cannot tolerate dopaminergic therapy, he said. "Perhaps we now have another treatment option if you're going to take a patient off a dopamine agonist because of side effects," Dr. Clarke said. "But I'd need more data before deciding to use this medication."

Another neurologist at the meeting commented on the data showing that impulsive behavior remained in 65% of the patients, including 4 (17%) with no improvement.

"There is a significant reduction in adverse events, but I think the impulsive behaviors can't be tolerated at all," said Cheryl Waters, MD, a neurologist at Columbia University Medical Center in New York. "I think the authors need to redo the study and take these patients off the dopamine agonists."

The data did not show how many of these patients had discontinued dopaminergic medication.

Dr. Waters previously co-wrote an article (Mov Disord. 2004;19:426-432) about the benefits of orally disintegrating selegiline in patients with PD. She was not involved with the current study.

Zelapar, according to its manufacturer, Valeant Pharmaceuticals, uses the freeze-dried Zydis technology to allow the tablet to rapidly dissolve on the tongue and absorb through the oral mucosa, bypassing the gut. Contraindications are the same as for other monoamine oxidase inhibitors, including narcotic pain medications and another monoamine oxidase inhibitor.

Dr. Pahwa and Dr. Lyons have disclosed that they have served as consultants and speakers for Valeant Pharmaceuticals. Dr. Pahwa also consults for Boehringer Ingelheim, and Dr. Lyons is a consultant for GlaxoSmithKline. Dr. Waters said she has been a speaker for Valeant. Dr. Clarke has disclosed no relevant financial relationships.

12th International Congress of Parkinson's Disease and Movement Disorders: Abstract 636. Presented June 25, 2008.

Pearls for Practice

  • In patients with PD who experience at least 1 adverse effect, the use of selegiline (orally disintegrating form) with concurrent dose reduction in anti-Parkinson's medication for 12 weeks is associated with reduction in daytime sleepiness in 68%, hallucinations in 36%, pedal edema in 46%, and impulsiveness in 48%, and complete resolution of the adverse effects in 22%, 57%, 23% and 35%, respectively.
  • Selegiline without other medication is preferred by 34% of PD patients, dopamine agonist alone by 4%, and combination therapy by 62%, with no significant reduction in symptoms of PD with the different therapies used.

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