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Treating Morning OFF Episodes in Parkinson’s Disease - Episode 2

The Advent of On-Demand Therapies in Parkinson Disease

A brief overview of clinically available on-demand therapies used to manage morning OFF episodes in patients with Parkinson disease.


Peter A. LeWitt, MD: With regard to managing Parkinson disease, we now have the opportunity to take care of morning OFF episodes. We have therapy available that can do better than just oral immediate-release levodopa. Among those options are what we can call on-demand treatments, medications that can be used at any time of the day but especially first thing in the morning to get a patient back into an ON state from the overnight OFF state that they have because of not taking medication for many hours since the evening before. We have 3 products that are available. Two of them involve apomorphine, a dopaminergic agonist that can be administered either subcutaneously by injection or sublingually by a strip that is placed under the tongue. And we also have another option, levodopa in a micropowder form that can be inhaled and absorbed through the lungs. Each of these so-called rescue therapies, on-demand therapies, can be used by the patient to increase the likelihood of being ON within a short period, in contrast to the delays that can be part of levodopa oral administration.

For an on-demand therapy, the most important attributes would be first the ease of use, the reliability, and perhaps freedom from adverse effects. These medication options are designed for rapidity of effect, and it might be that that speedy onset of dopaminergic effect, whether from inhaled, or injected, or sublingually absorbed, the rapidity of effect might cause some of the dopaminergic adverse effects, such as nausea, a drop in blood pressure, that can occur with medication of this class being rapidly absorbed and going to work.

Patients would choose among these therapies based on their experience, their ease of using it, perhaps because in the case of levodopa it’s the same drug that they are also taking in oral form, perhaps in the case of apomorphine injections because they can adjust the dose for a little more, a little less based on their experience. But whatever the individualization going on, the patient now has 3 options to choose among, each of which is designed to go to work more rapidly than their oral levodopa medication, which has a minimum absorption time on an empty stomach of 15 or 20 minutes as clinical research has shown.

Transcript edited for clarity.