CHICAGO – In a group of patients with motor fluctuations and dopamine agonist-related side effects, adding orally disintegrating selegiline and decreasing the dopamine agonist dose reduced these adverse events without worsening Parkinson's disease symptoms.
According to self-reports from the first 50 patients in a 12-week, multicenter, open-label study, daytime sleepiness (defined as a score greater than 10 on the Epworth Sleepiness Scale) was present in 41 patients at baseline and, of those, was reduced in 28 (68%) and resolved in an additional 9 (22%) at study completion.
Symptoms were also reduced or resolved for 14 patients with hallucinations (36% reduced, 57% resolved), 22 patients with pedal edema (46% reduced, 23% resolved), and 23 patients with impulsive behavior including gambling, sexual urges, eating, and buying (48% reduced, 35% resolved), Dr. Rajesh Pahwa reported on behalf of the investigators of the A to Z Study in a poster at the 12th International Congress of Parkinson's Disease and Movement Disorders.
Motor scores on the Unified Parkinson's Disease Rating Scale (UPDRS) were not significantly different at baseline and week 12, reported Dr. Pahwa, who serves as director of the Parkinson's disease and movement disorder center at the University of Kansas Medical Center, Kansas City.
However, Dr. Pahwah and colleagues found that significant reductions from baseline were observed in the UPDRS activities of daily living scores (11.9 at baseline vs. 10.2 at week 12) and mentation scores (2.4 at baseline vs. 1.9 at week 12).
Orally disintegrating selegiline (Zelapar) is indicated as adjunctive therapy in Parkinson's disease patients who exhibit deterioration in their response to levodopa. There is no evidence from controlled trials that the monoamine oxidase type B inhibitor has any beneficial effect in the absence of concurrent levodopa therapy.
Patients in the study had idiopathic Parkinson's disease with levodopa-induced motor fluctuations that required reductions in the dopamine agonist (DA) dosage because of adverse events. In Dr. Pahwa's clinical experience, the addition of orally disintegrating selegiline in such patients has reduced the side effects of DA because it allows for a reduction in DA dose.
“I proposed the study based on my clinical experience with dopamine agonists and Zelapar, and the results of the study confirmed my clinical experience,” Dr. Pahwa said in an interview.
About 25%-30% of patients treated with DAs experience somnolence; 40% have pedal edema, 15%-20% have hallucinations, and 5% have impulse disorders, he said.
At baseline, 29 (58%) of the first 50 patients in the study were taking pramipexole (mean dosage, 2.3 mg/day) and 21 (42%) were taking ropinirole (mean dosage, 10.6 mg/day).
The final mean pramipexole dosage was 0.5 mg/day and the mean ropinirole dosage was 3.0 mg/day.
The DA dosage was cut in half within 1 week of baseline, and orally disintegrating selegiline (1.25 mg once daily) was added. At week 3, if DA-related adverse events persisted and efficacy was unchanged, the DA dosage was tapered to discontinuation, and orally disintegrating selegiline was continued. At week 6, orally disintegrating selegiline was increased to 2.5 mg/day.
If the DA dosage was not discontinued and DA-related adverse events were still present with efficacy unchanged, the DA dosage was further reduced. At the final visit, 44 patients were taking 2.5 mg/day orally disintegrating selegiline, and 6 patients were taking 1.25 mg/day, according to Dr. Pahwa.
Adverse events were assessed at baseline and at weeks 3, 6, and 12 by self-report, as well as by the Epworth Sleepiness Scale, the Neuropsychiatric Inventory, the Barratt Impulsiveness Scale, and ankle circumference.
The study was supported by Valeant Pharmaceuticals International, which markets Zelapar. Dr. Pahwa is a consultant and speaker for and has received research grants from Valeant, Boehringer Ingelheim GmbH, and GlaxoSmithKline.