Parkinson’s disease OFF episodes: cause, treatment and prevention



Parkinson’s disease (PD) is a neurological disorder that gradually gets worse over time. It causes motor symptoms, such as slowed movements, muscle stiffness, and tremors. It can also cause non-motor symptoms, such as anxiety, fatigue, and difficulty concentrating.

The standard treatment for PD is levodopa. This drug is often combined with carbidopa in a single pill or capsule. Carbidopa makes levodopa more effective.

Levodopa / carbidopa can help relieve the symptoms of PD. But with time, Most people who receive this treatment begin to experience OFF episodes, when their symptoms return or worsen.

Read on to learn more about OFF episodes and how they can be handled.

The ON / OFF phenomenon in PD occurs when a person experiences flare-ups between regular doses of levodopa.

During an ON episode, levodopa works well and symptoms improve. During an OFF episode, levodopa does not work and symptoms return or worsen.

A 2018 review found that 25 to 50 percent of people with PD developed OFF episodes within 2 years of starting levodopa treatment. Within 10 years of starting treatment, most people with PD have had episodes of OFF.

OFF episodes can affect different people in different ways. They can follow a predictable pattern or occur in an unpredictable way. They can set in suddenly or gradually.

Researchers behind a 2021 survey found that OFF episodes were linked to reduced quality of life in people with PD. OFF episodes can limit your ability to move around and perform routine activities. They are also associated with increased anxiety and depression.

More research is needed to understand the cause of OFF episodes. Experts believe that fluctuations in dopamine levels play a role.

Dopamine is a neurotransmitter that carries signals between nerve cells. Low levels of dopamine contribute to the symptoms of PD.

When you take levodopa, your body converts it to dopamine. This reduces the symptoms of PD. As your body uses each dose of levodopa, your dopamine levels start to drop. This drop in dopamine can cause an OFF episode.

Many people with PD also have gastrointestinal complications that interfere with their ability to absorb oral medications. If you are taking oral levodopa, it may take some time for your body to absorb the medicine. This can lead to a delayed ON episode.

Eventually, most people with PD develop OFF episodes. Some people develop OFF episodes earlier than others.

Researchers have found some evidence that taking large doses of levodopa can increase your risk of OFF episodes. This can cause your dopamine levels to fluctuate more dramatically.

It is important that your doctor prescribes the lowest dose of levodopa needed to manage your symptoms. This can help limit fluctuations in dopamine and lower your risk of OFF episodes.

If you think you might have OFF episodes, notify your doctor. They may adjust the dose or formulation of levodopa / carbidopa prescribed for you. They may also prescribe other treatments to manage the OFF episodes.

If you are experiencing OFF episodes, your doctor may recommend one or more changes to your treatment plan.

They can:

  • Adjust the prescribed dose or formulation of oral levodopa / carbidopa. They may recommend lower and more frequent doses of oral levodopa / carbidopa. They may prescribe an extended-release formula rather than a quick-acting option.
  • Recommend enteral levodopa / carbidopa. This type of levodopa / carbidopa is continuously infused through a tube into your intestinal tract to provide a constant flow of medicine. It requires surgery to insert the tube.
  • Prescribe an adjunct maintenance medication. Adding one or more adjunct drugs to your daily treatment plan may help improve symptom relief during ON episodes. It can also reduce the frequency and duration of OFF episodes.
  • Prescribe rescue medication. When OFF episodes occur, taking a quick-acting reliever medication like sublingual apomorphine strips can provide quick relief. You take rescue medication as needed, rather than on a regular schedule.

In some cases, your doctor may recommend deep brain stimulation (DBS). In this procedure, a surgeon implants electrodes in the brain and a small internal pulse generator in the chest or abdomen. The internal pulse generator sends electrical signals to the brain to help control the symptoms of DB.

Each treatment option carries a different risk of side effects. Ask your doctor about the potential benefits and risks of different treatment approaches.

Over time, most people with PD begin to experience OFF episodes when the levodopa / carbidopa drug does not work well and their symptoms return or worsen. These episodes can negatively affect the quality of life.

If you think you are having OFF episodes, tell your doctor. For example, contact them if you wake up with bothersome symptoms or if you have symptoms that come back or get worse between scheduled doses of levodopa / carbidopa. Let them know if it takes a long time for one dose of levodopa / carbidopa to get relief.

They may adjust the dose or formulation of levodopa / carbidopa that has been prescribed for you. They may also prescribe treatments as needed to help prevent and relieve symptoms of OFF episodes.


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