Managing OFF Episodes

What Are Off Episodes?

Parkinson’s disease is characterized by a lack of dopamine, a signaling molecule in the brain. One common approach to manage the tremors, stiffness, and slowness of Parkinson’s disease is to replace the missing dopamine with levodopa. Levodopa is a medication that is converted to dopamine within the brain. However, the effects of levodopa may begin to wear off early with long-term use.
The period of time during which levodopa controls the symptoms of Parkinson’s disease is called “on-time.” When the medication stops working, symptoms reappear and a so-called “off episode” starts. Off episodes may occur predictably, such as right before you are due to take your next dose, or they may happen suddenly and unexpectedly.

Initially, off episodes may be controlled by increasing the dose of levodopa or by increasing how often you take the medication. However, the dose cannot be increased too much because high doses of levodopa can lead to the development of dyskinesia, or uncontrolled and abnormal movements. Off episodes increase in frequency over time as Parkinson’s disease progresses. After 4 to 6 years of treatment, 40% of patients with Parkinson’s disease report off episodes, and nearly all patients experience them after 10 years. Patients may experience both motor and non-motor symptoms during an off episode.

Table: Common motor and non-motor symptoms during off episodes

Managing Off Episodes

While off episodes are part of the normal progression of Parkinson’s disease, there are things you can do to help manage or reduce these episodes.

- Track your off episodes in a diary. Recording your symptoms and when they occur can help your doctor manage your medications.
- Change your medication regimen. Your doctor may change the dose of levodopa or how often you take it. A new medication may be added to better control your symptoms.
- Adjust your diet. What you are eating and when may impact the absorption of your medications. Talk to your doctor to determine if changing your diet may help manage off episodes.
- Take a “rescue” medication. There are several medications available that are designed to quickly reverse off episodes in 15 minutes or less.

Rescue Medications

On-demand, rapid-acting medications can provide quick symptom control during an off episode. Levodopa is available in an inhaler for rapid administration during an off episode and starts to work in as soon as 10 minutes.

Apomorphine is a medication that mimics the actions of dopamine in the brain. Apomorphine is available as a subcutaneous injection that is administered under the skin. It is also available as a sublingual film that rapidly dissolves under the tongue. These medications improve symptoms within 15 minutes and may be used up to 5 times a day. Other medications, such as COMT inhibitors or MAO-B inhibitors which boost dopamine, may also be required to reduce or prevent off episodes.