Off Episodes

Parkinson’s disease is characterized by a lack of dopamine, a signaling molecule in the brain, which leads to tremors, stiffness, and slowness.

One approach to treat the disease is to replace the missing dopamine. But it’s too large a molecule to cross the blood-brain barrier, so a dopamine precursor called levodopa — which can enter the brain — is used instead. Inside the brain, levodopa is converted into active dopamine, easing motor problems in people with Parkinson’s.

However, with long-term use these beneficial effects wear off before a new dose can be taken.

What are off episodes?

The period when levodopa has a positive effect on Parkinson’s symptoms is called “on” time. Once the medication stops working, a so-called “off” episode starts, where symptoms recur.

Ideally, levodopa should be given in a way that prevents off episodes between doses. The problem is that with prolonged use, the body’s ability to convert levodopa into dopamine decreases lowering the medication’s efficacy. This can be compensated up to a certain degree by increasing the dose of levodopa or by increasing the dosing frequency. But the extent to which doses of levodopa can be increased is limited; high doses of the medication cause dyskinesia, or uncontrolled and abnormal movements.

Managing off episodes

Apokyn (apomorphine) is a medication that is given between doses of levodopa treatment to help reduce symptoms during off episodes. Apokyn is a dopamine agonist, which means that it imitates the action of dopamine in the brain. It is injected under the skin and acts within 20 minutes of administration.

Because an injection of Apokyn can cause skin irritations, Sunovion Pharmaceuticals developed a sublingual (under the tongue) formulation of apomorphine (APL-13077). The company applied for APL-13077’s approval with the U. S. Food and Drug Administration (FDA) in April 2018. But the FDA declined to approve APL-13077 based on that application in February, requesting instead additional information. The agency did not require new clinical tests.

Another way to reduce off episodes is to increase the time that levodopa is working and active in a person. To achieve this, the medication is combined with an agent called carbidopa that helps to prevent levodopa’s breakdown. The medication Sinemet contains levodopa and carbidopa, and is commonly used to treat motor symptoms of Parkinson’s disease. A controlled-release (CR) formulation of the medication further extends the time that levodopa is active and reduces the dosing frequency.

To achieve optimal dosing and frequency, it is recommended that patients keep a medication diary. In this diary, they should record how long it takes for levodopa to kick in and to wear off. With this information, the dosing frequency can be adjusted, and off episodes avoided. Keeping a diary also decreases the risk of an overdose, which can cause dyskinesia.


Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

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