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, fatigue, and difficulty concentrating.

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.

Levodopa/carbidopa 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.

Read on to learn more about OFF episodes and how they may be managed.

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

During an ON episode, the levodopa is working well and symptoms improve. During an OFF episode, the levodopa isn’t working and symptoms return or get worse.

A 2018 review found that 25 to 50 percent of people with PD 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. 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.

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 of PD. As your body uses up each dose of levodopa, your dopamine levels begin to fall. This drop in dopamine may cause an OFF episode.

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 delayed ON episode.

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.

They may:

  • Adjust your 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 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 during ON episodes. It may also 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.

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 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 medication levodopa/carbidopa doesn’t work well and their symptoms return or worsen. These episodes can negatively affect quality of life.

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

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.