Fact Sheets

Managing "Off" Time in Parkinson's

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“Off” Time – periods when the effects of medication (typically levodopa) wear off and symptoms return or worsen.

"Off" time in Parkinson’s can include:

Early morning “off,” before the first dose kicks in
Middle-of-the-night “off” when the evening dose wears off
Unexpected “off” not related to when you take your medications
“Off” after a big or protein-rich meal
Delayed “on” due to constipation or slow digestion (these can affect how medication works)
Dose failure when a single medication dose does not work at all

Medications like levodopa, commonly used for Parkinson’s disease (PD), usually help manage symptoms reliably for several years or longer. As PD progresses, the brain's response to these medications may change. This can lead to symptom fluctuations, known as "on" and "off" periods. "On" periods are times when the medication is working well, or symptoms are less noticeable. "Off" periods are times when the medication's effects wear off, and symptoms return or worsen.

If this is a problem for you, there are medication adjustments, lifestyle changes and other treatment options that you and your care team can explore. These steps can often help decrease "off" time and improve quality of life.

Quick Facts

PD causes brain cells that produce dopamine — a key chemical for regulating movement, mood and motivation — to gradually break down and die.
PD medications improve symptoms by replacing, mimicking or boosting dopamine.
While some medications influence dopamine activity, levodopa is the only one that turns into dopamine in the brain.
As PD progresses, people often become more sensitive to levodopa and other medications, which can lead to increased side effects.

Understanding "Off" Time

As Parkinson’s progresses, the brain's ability to produce and store dopamine decreases. This can cause drugs like levodopa that replace, mimic or boost dopamine (known as dopaminergic medications) to "wear" off more quickly or sometimes not work at all.

Wearing-off symptoms vary for each person. People often feel slower or stiffer, and tremor might return or worsen. Some people experience "freezing" episodes or muscle contractions (dystonia). Non-movement symptoms like anxiety, depression, fatigue, foggy thinking and pain may also appear or intensify. Any symptom that improves with dopaminergic medication, can also worsen as the medication wears off.

"Off" periods are usually more noticeable with immediate-release levodopa because it has a strong and rapid initial effect that wears off quickly compared to other slower-acting medications. This can lead to more pronounced symptom fluctuations throughout the day.

Treatment for “Off” Time

Managing "off" time usually involves many approaches:

Track symptoms
Use a symptoms diary before doctor's appointments or when you notice changes. Note when "off" periods occur in connection to medication timing and other factors, such as stress, constipation or physical activity. To get started, visit Parkinson.org/SymptomsDiary.

Balance protein and medication
High-protein foods, when taken together with levodopa, can reduce the medication's effectiveness. If this is an issue for you, talk to your doctor about scheduling medications 30-60 minutes before or one hour after meals, or moving large protein meals to the end of the day. Constipation and slow digestion can also impact levodopa.

Manage medications
To lessen "off" time, your doctor may suggest the following:

Adjust medication timing or amounts. Sometimes taking a larger dose or more frequent doses can decrease "off" time.
Use slower-releasing medications to help keep dopamine levels more stable, including controlled or extended-release levodopa medications or dopamine agonists.
Try a quick-acting levodopa or apomorphine medication for unexpected or sudden “off” periods.
Add medications to help boost dopamine, including COMT inhibitors or MAO-B inhibitors.

Balancing symptom relief with potential side effects can be challenging. Work closely with your doctor to adjust your treatment and find what works best for you.

Explore deep brain stimulation (DBS)
DBS involves surgically implanting electrodes in the brain to deliver electrical impulses that disrupt abnormal brain activity. It may help certain people reduce "off" time when medications are not sufficient.

Tips for Managing “Off” Time

Take medications on time to reduce unpredictable "off" periods. Use timers to stay on schedule.
Help PD medications work. Drink plenty of water and eat fiber-rich foods to manage constipation.
Reduce stress with deep breathing, yoga and meditation.
Consider working around "off" periods instead of pushing through them. Enjoy a movie, audiobook or another low-activity pastime.

Books

Medications: A Treatment Guide to Parkinson’s Disease

The information included here will explain the types of medications available to manage motor and non-motor symptoms in the hopes that it will help you to work with your Parkinson’s specialist to find the right balance of medications to help you live well with Parkinson’s.

This book is only available digitally to view, download or print. It is also available in Kindle and audiobook formats.

Books

Managing PD Mid-Stride: A Treatment Guide to Parkinson's Disease

If managing your Parkinson’s has become more challenging than it used to be, the book Managing Parkinson’s Mid-Stride: A Treatment Guide to Parkinson’s is for you. This book explains why symptoms may get better and worse throughout the day and how to treat and cope with them. Find answers and read tips and stories that can help.

This book is only available digitally to view, download or print. It is also available in Kindle and audiobook formats.

Podcasts

Episode 5: How to Manage Parkinson’s “Off” Time

Parkinson’s can be unpredictable – symptoms can come and go or get better and worse throughout the day. These so-called “on-off” fluctuations (also called motor fluctuations) and dyskinesias can be troubling, but movement disorder specialists can help with the choice of medication, dosages, and timing. Dr. Irene Malaty explains more about what causes these changes and how you can work with your doctor to manage them.

Dr. Malaty is a fellowship-trained movement disorder specialist at the University of Florida in Gainesville, FL. She is the director of the Parkinson’s Foundation Center of Excellence at UF and is site primary investigator of the Parkinson’s Outcomes Project. Additionally, Dr. Malaty is co-director of the Tourette Association of America Southeast Regional Center of Excellence and runs the interdisciplinary Tourette and tic disorders clinic for children and adults. In all these initiatives, Dr. Malaty cares for patients, coordinates team-based care, and promotes clinical research. Dr. Malaty is the director of industry-sponsored trials at UF movement disorders.

Dr. Malaty serves on the executive board of the Florida Society of Neurology, on the executive committee of the American Academy of Neurology Neuroendocrinology Section, as the Movement Disorder Subsection Chair, and on the Tourette Association of America Medical Advisory Board. She has specific interests in the non-motor aspects of Parkinson’s disease and Tourette’s syndrome and in using botulinum toxin to treat neurological conditions. She has written many peer-reviewed articles, is involved in numerous clinical trials in movement disorders, and enjoys lecturing on Parkinson’s disease, Tourette, botulinum toxin administration, dystonia, and other movement disorders.

She studied microbiology and psychology at Indiana University in Bloomington, IN, and attended Indiana University School of Medicine. After completing a transitional year of medicine at St. Vincent’s hospital in Indianapolis, she moved to Gainesville for neurology residency and served as chief resident. She completed a fellowship in movement disorders at the University of Florida and joined the faculty thereafter.

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For all of our Substantial Matters podcast episodes, visit Parkinson.org/Podcast.

Podcasts

Episode 148: How to Prevent Sudden “Off” Episodes

“Off” episodes can become a troubling aspect of Parkinson’s disease (PD), especially as the disease progresses. These are periods in the day when the effect of levodopa medication wears off, either suddenly or gradually, with a return of motor or non-motor symptoms.

The good news is that there are several ways to try to minimize “off” episodes, including medication timing, medication adjustments, and add-on medications. In this podcast episode, Dr. George Kannarkat, a movement disorders fellow at the University of Pennsylvania in Philadelphia, a Parkinson’s Foundation Center of Excellence, discusses “off” episodes, their causes, strategies that people can use today to minimize them, and what new technologies are here or coming along to help lessen them.

Released: April 4, 2023

Dr. George Kannarkat is an MD-PhD trained physician-scientist who is currently finishing his Movement Disorders fellowship at the University of Pennsylvania. After fellowship, he will be staying at the University of Pennsylvania as an Instructor to continue seeing individuals with Parkinson's disease while concurrently working in the lab of Dr. Alice Chen-Plotkin. His research interests are understanding the molecular mechanisms, particularly those outside the brain, that contribute to initiating pathology seen in Parkinson's disease. His ultimate goal is to help develop technologies that identify and treat disease in early or prodromal stages. He completed medical school and his graduate training at the Emory University School of Medicine where he worked in the lab of Dr. Malu Tansey to work on peripheral immune mechanisms of neurodegeneration. He completed his neurology residency at Johns Hopkins Hospital.