Current Treatment of OFF Episodes

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Predictable OFF episodes (i.e. end of dose wearing off) can be treated by increasing the dose or frequency of levodopa or by adding adjunctive Parkinson's disease (PD) medications (COMT inhibitors, MAO-B inhibitors, dopamine agonists). However, over time this becomes less effective and patients continue to suffer from six or more hours a day of total daily OFF time despite being on multiple PD medications and frequent doses of levodopa. Importantly, studies have shown that approximately two-thirds of a PD patient's daily OFF time is spent waiting for their medication to work (due to delayed ON/dose failure) compared to one-third being due to end of dose wearing OFF.

There is only one approved treatment to address this "waiting to turn ON" as well as end of dose wearing OFF, which is apomorphine. Apomorphine is a dopamine agonist that acts on dopamine receptors to rapidly convert a patient from the OFF state to the ON state. Apomorphine is currently only approved as a subcutaneous injection and although efficacious, it has limited use since it may be difficult for a PD patient to deliver and can be painful.