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September 28, 2022
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PD therapy for off time depends on safety, efficacy, patient preference

Fact checked byHeather Biele
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LAS VEGAS — When evaluating the best choice for on-demand therapies for off time in Parkinson’s disease, physicians should consider severity of side effects, time to efficacy and patient preference, a presenter stated at BRAINWeek 2022.

Greg Pontone

“There are symptomatic treatments that help the day-to-day disability, and then for Parkinson’s at least, there’s the Holy Grail, the disease-modifying therapies,” Greg Pontone, MD, MHS, director of the Parkinson’s Disease Psychiatric Clinic at Johns Hopkins University School of Medicine, said during his presentation. “I would argue ... if you look across the movement disorders, we have the best symptomatic therapies.”

Source: Adobe Stock.
Source: Adobe Stock.

According to Pontone, most patients with PD are between stages 2 and 4 on the Hoehn and Yahr Stage scale —moderate disease progression in which balance, reflexes and muscle issues require assistance with standing and walking — rarely progressing to stage 5 before associated comorbidities result in death. This is the period in which symptomatic therapies are targeted for individuals with PD, he said.

However, Pontone continued, these levodopa-based therapeutics carry with them the possibility of induced dyskinesia in upper and lower extremities, as well as fluctuations in the on-off cycle of symptoms where motor issues return or worsen in the transition between on and off times or beneficial effects during on times lessen.

Pontone stated that duration of the disease, and not exposure to levodopa itself, is thought to be the main factor in developing motor complications. As such, he noted that neurologists will manage medication so the duration between on and off times is lessened, and effects of the transition are mollified.

“Just giving people more levodopa isn’t a solution,” Pontone said.

As systematic therapies aim to improve function within the boundaries of PD, and dyskinesia occurs most when medication begins to wane, patients should keep a detailed journal to track off periods and note the difference in both emotion and motion that accompanies those off times.

Pontone offered examples of three current in-demand therapies for off episodes: subcutaneous apomorphine, sublingual apomorphine and inhaled levodopa powder.

Patients may encounter the most obstacles with subcutaneous apomorphine, including the need for office visits for titration, administration of an antiemetic and caregiver assistance to assemble the injector, but benefit from a 15-minute onset.

Sublingual apomorphine allows titration from home as well as ease of patient administration, but may require 90 minutes to take effect.

Inhaled levodopa is administered in a relatively low dose with two puffs from an inhaler and can be initiated when off period symptoms return but can take anywhere from 30 to 60 minutes to be effective.

Pontone added that, even with prolonged dosing, the period between on and off times tends to shrink while unpredictability of symptoms increases, particularly dyskinesia during on times. Future research and development of therapeutics aim to address these gaps.

“I can tell you symptomatic therapy has absolutely improved over the years, and now we have an answer — not a perfect answer — but an answer for most of the things that cause disability and distress in patients,” Pontone said.