You may experience Parkinson’s symptoms that seem to come and go or get more severe when you take the drug levodopa. This is how you can manage those symptoms when you’re taking the medication.

Parkinson’s disease (PD) is a neurological disorder that gradually worsens over time. It causes motor symptoms, such as slowed movements, muscle rigidity, and tremors. It can also cause non-motor symptoms, such as anxiety, dry skin, and trouble sleeping.

The gold-standard treatment for PD is levodopa. This medication is often combined with carbidopa in a single pill or capsule. Carbidopa makes levodopa more effective in treating Parkinson’s symptoms.

This medication can help relieve symptoms of PD. But over time, most people who receive this treatment begin to experience OFF episodes, when their symptoms return or worsen. This can happen between doses or at different times during the day.

The ON/OFF phenomenon in PD happens when someone experiences flares of symptoms between regularly scheduled doses of levodopa.

When you first start using levodopa, the Parkinson’s symptoms may improve for several hours after you’ve taken that dose. If your symptoms return or get worse between scheduled doses, you may suddenly experience symptoms again after taking the medication.

This is known as an OFF period or episode.

Sometimes, medication does not relieve OFF episodes for several hours, and that time period can vary for different people.

A 2018 review focusing on 40 years of Parkinson’s research found that 25% to 50% of people developed OFF episodes within 2 years of beginning treatment with levodopa. Within 10 years of starting treatment, most people with PD had OFF episodes.

OFF episodes can affect different people in different ways.

They may follow a predictable pattern or occur unpredictably, or they may set in suddenly or gradually.

The researchers behind a 2021 survey found that OFF episodes were linked to reduced quality of life in people with PD. OFF episodes may limit your ability to get around and do routine activities. They’re also associated with increased anxiety and depression.

Spme people may have anxiety and apprehension when they start to experience frequent OFF episodes. After getting used to a predictable levodop response, they don’t know when their symptoms may return. That can make it more difficult to anticipate what they may feel like during that particular day.

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 symptoms of PD.

When you take levodopa, your body converts it into dopamine. This reduces symptoms.

After 2 to 6 hours of consuming the medication, you will need another dose so that your body can convert it to dopamine. Long-acting formulations work for longer periods of time before you need another dose. When the medication wears off and your dopamine level is low again, you may experience recurring “OFF” symptoms.

Years of taking levodopa can mean that your body makes dopamine at a different rate or uses the medication at a different rate, making the effective timing less predictable.

Many people with PD also have gastrointestinal complications that interfere with their ability to absorb oral medications If you take oral levodopa, it may take some time for your body to absorb the medication. This may lead to a delay in the medication’s effects on symptoms.

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

Researchers have found evidence that taking high doses of levodopa may increase your risk of OFF episodes. It may cause greater fluctuations in your dopamine levels.

It’s important for your doctor to prescribe the lowest dose of levodopa necessary to manage your symptoms. This may help limit fluctuations in dopamine and reduce your risk of OFF episodes.

If you think you might be experiencing OFF episodes, let your doctor know. They may adjust your prescribed dose or formulation of levodopa/carbidopa. They may also prescribe other treatments to manage OFF episodes.

If you’re experiencing OFF episodes, your doctor may recommend one or more changes to your treatment plan:

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

Pump infusion therapy

New research advances and technology is making Parkinson’s disease, including these OFF episodes, more manageable.

One of the latest developments comes in the form of pump infusion therapy, which involves using a device to continuously stream a Parkinson’s medication into your body rather than taking it by injection or pill form.

Since October 2024, the Food and Drug Administration (FDA) has approved 2 new devices that allow for a continuous stream of medication to help treat and lessen these OFF episodes for people with Parkinson’s.

  1. Vyalev: an under-the-skin, continuous infusion of the medication levodopa, aimed at lessening the times Parkinson’s symptoms reappear. Clinical research showed roughly 3 additional hours of “on” time for people with advanced Parkinson’s, compared to only 1 hour of added time for people taking the medication orally. This device by AbbVie was the first of its kind approved by the FDA.
  2. Onapgo: an under-the-skin device made by Supernus Pharmaceuticals that provides a constant supply of the medication apomorphine, another prescription drug used to treat advanced Parkinson’s OFF symptoms. Research involved in the FDA’s approval found that those who received Onapgo therapy experienced nearly 2 hours less “off” time and nearly 3 hours more managed symptoms each day, compared to those who didn’t use the treatment.

These are medical devices that contain specific medications and may not be appropriate for everyone with Parkinson’s. Your healthcare team can help you understand what options may be best for you.

Deep brain stimulation

In some cases, your doctor may recommend deep brain stimulation (DBS), a surgical approach that uses a neurostimulator to help manage Parkinson’s symptoms.

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 manage symptoms.

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 Parkinson’s disease begin to experience OFF episodes when the medication levodopa/carbidopa wears off too quickly, doesn’t work well, or the timing of its effects becomes unpredictable. This leads to Parkinson’s symptoms seeming to return or get worse.

Let your healthcare team know if it has been taking longer than usual for your medication doses to start working or if symptoms seem to reappear or get worse more quickly.

They may adjust your prescribed dose or formulation of levodopa/carbidopa. They may also prescribe as-needed treatments to help prevent and relieve symptoms of OFF episodes.