How to Talk with Your Doctor About Parkinson’s OFF Episodes

OFF episodes are periods of time between scheduled doses of levodopa/carbidopa when the medication isn’t working well and your symptoms reappear or get worse.

Common types of OFF episodes include:

• Morning OFF. You wake up in an OFF episode, before taking your first dose of levodopa/carbidopa for the day.
• Wearing OFF. After taking a dose of levodopa/carbidopa, it gradually wears off and your symptoms get worse before your next scheduled dose of medication.
• Delayed ON. There’s a significant delay from the time that you take a dose of levodopa/carbidopa to the time that your symptoms improve.
• Unpredictable or sudden OFF. You suddenly enter an OFF state, following no apparent pattern.

An estimated 25 to 50 percent of people with PD begin to have OFF episodes within 2 years of starting treatment with levodopa/carbidopa, according to a 2018 review. The majority of people with PD begin to experience OFF episodes within 10 years of starting treatment.

Although OFF episodes are common, they can be managed. Your doctor may adjust your treatment plan to help limit the frequency, duration, and severity of OFF episodes.

During OFF episodes, you might experience a flare of motor symptoms, non-motor symptoms, or both.

Examples of motor symptoms include:

• tremor
• muscle rigidity
• muscle weakness
• muscle cramps
• reduced coordination or dexterity
• difficulty standing, walking, or maintaining your balance

Examples of non-motor symptoms include:

• pain
• fatigue
• anxiety
• difficulty concentrating
• feeling too hot or too cold
• difficulty swallowing
• difficulty controlling your bladder or bowels
• shortness of breath
• unusual sweating

Symptoms can vary during OFF episodes. The symptoms may set in gradually or suddenly. They may follow a predictable pattern or not.

Let your doctor know about any fluctuations in symptoms that you experience. They can help you learn if those changes are related to OFF episodes or another cause, such as medication side effects or progression of PD.

You might find it helpful to keep a symptom diary, by tracking the:

• dosage and timing of medication that you take each day
• symptoms that you experience each day
• timing and duration of those symptoms

Reviewing this diary may help you and your doctor identify OFF episodes and their potential causes. Pinning down the cause of changes in your symptoms can be frustrating. Whether or not they’re related to OFF episodes, you can look at adjusting your treatment plan.

It’s important to let your doctor know about any changes in your condition over time. They can help you understand and weigh your treatment options. Together, you can decide which treatment is right for you.

Let your doctor know if:

• You wake up in the morning with bothersome symptoms.
• You notice that your symptoms get worse before a scheduled dose of medication.
• There’s a delay from the time you take medication to the time you experience symptom relief.
• You have sudden and unpredictable flares of symptoms.
• Your symptoms have changed or gotten worse.

Ask your doctor:

• Are your symptoms a sign of OFF episodes or another cause?
• Are there changes that you could make to your treatment plan to improve symptom management?
• What are the potential benefits, risks, and costs of different treatment options?

You might also find it helpful to save this article or other resources about OFF episodes to discuss with your doctor. If you have questions about OFF episodes or other aspects of your condition, ask your doctor to help you learn more.

Considering writing down a list of your questions and concerns before each appointment. This may help you get the information and support that you need from your doctor to manage OFF episodes and other aspects of PD. You can even take a video while symptoms are flaring to show your doctor.

If you don’t understand something that your doctor tells you, ask them to explain it again in simpler terms. It may also help to bring a trusted friend, family member, or caregiver with you to your appointment. They can offer emotional support, help take notes, and provide other assistance.

If you’re experiencing OFF episodes, your doctor’s recommended treatment plan will depend on factors such as:

• the timing and duration of your symptoms
• your overall health and risk of side effects
• your treatment goals, preferences, and history
• your insurance coverage and healthcare budget

Your doctor may prescribe a combination of maintenance and rescue medications to manage OFF episodes.

You take maintenance medications on a regularly scheduled basis to reduce the frequency and duration of OFF episodes. You take rescue medications to treat OFF episodes when they do occur. In some cases, your doctor may also recommend a procedure known as a deep brain stimulation (DBS) to help limit symptoms of advanced PD.

Learn more about these treatments below. Then, ask your doctor about the potential benefits, risks, and costs of different treatment approaches. Let them know what your treatment goals and priorities are.

Levodopa/carbidopa

Progression of Parkinson’s disease and taking levodopa/carbidopa may increase your risk of OFF episodes. To limit OFF episodes, your doctor may recommend changes to your prescribed dose or formulation of levodopa/carbidopa.

They may switch you from short acting formulations of oral levodopa/carbidopa to a longer-acting option.

In some cases, they may recommend continuous infusions of enteral levodopa/carbidopa. This type of levodopa/carbidopa is pumped directly into your intestinal tract. If you choose to receive this treatment, you’ll need to have a tube surgically implanted in your abdomen for medication delivery.

Adjunct maintenance medication

In addition to levodopa/carbidopa, your doctor may prescribe one or more of the following medications alongside your levodopa/carbidopa to help limit symptoms of PD and OFF episodes:

• Dopamine agonist: bromocriptine (Parlodel), pramipexole (Mirapex), ropinirole (Requip), rotigotine (Neupro)
• Catechol-O-methyltransferase (COMT) inhibitor: entacapone (Comtan, Stalevo), opicapone (Ongentys), tolcapone (Tasmar)
• Monoamine oxidase B (MAO-B) inhibitor: selegiline (L-deprenyl, Eldepryl, Zelapar), safinamide (Xadago), rasagiline (Azilect)
• Anticholinergic: benztropine (Cogentin), trihexyphenidyl (Artane)
• Adenosine antagonist: istradefylline (Nourianz)
• N-methyl-D-aspartate (NMDA) antagonist: amantadine (Gocovri, Osmolex, Symmetrel)

Taking adjunct maintenance medication may help limit the frequency of OFF episodes for some people.

Rescue medication

To relieve symptoms of OFF episodes when they do occur, your doctor may prescribe a fast-acting rescue medication, such as:

• injectable apomorphine hydrochloride, which you inject under your skin (Apokyn)
• sublingual apomorphine hydrochloride, which you place under your tongue as a dissolving strip (Kynmobi)
• levodopa powder, which you inhale (Inbrija)

These medications provide quick relief of symptoms.

Deep brain stimulation

In DBS, a surgeon implants electrodes in the brain and a special device in the chest or abdomen. That device sends electrical signals to the brain to help control motor symptoms of PD.

A 2020 study followed 30 people with advanced PD who had begun treatment with DBS more than eight years earlier. Those people had fewer OFF episodes one year after starting treatment with DBS, compared with before. They continued to have fewer OFF episodes eight years later.

Like any type of surgery, DBS carries a risk of potentially serious side effects.

The symptoms of PD progress over time. Regular checkups and open communication with your doctor are essential for managing the condition on an ongoing basis.

Among other changes to your condition, you may begin to experience OFF episodes between regularly scheduled doses of medication. These episodes can cause symptoms that negatively affect your quality of life.

Let your doctor know if you think you might be experiencing OFF episodes. They can help you identify the potential cause and recommend changes to your treatment plan to help prevent and relieve OFF episodes.