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Parkinson’s disease can throw frustrating curveballs, like sudden stiffness or tremors that slow you down right when you need to be on top of your game. These unexpected slowdowns are called motor fluctuations, but here’s the good news: they’re a well-understood part of Parkinson’s, and there are ways to manage them.

This blog will be a roadmap to smoother movement and a more confident you. Let’s unlock the secrets of “on” and “off” periods and discover strategies to regain control of our day.

Motor Fluctuations in Parkinson’s Disease

Motor fluctuations in Parkinson’s disease refer to the ups and downs in a person’s movement capabilities throughout the day. It’s like a switch that controls our mobility. Sometimes it’s “on” and other times it’s “off.” It can also lead to frustration and affect our relations with others. So what happens during these phases? Let us take a closer look:

  • During “On-Time,” medications are effective, and we have better control over our movements. It makes our daily tasks easier and allows us to function more normally.
  • Conversely, the “Off-Time” represents periods as the medication wears off. Symptoms like stiffness, tremors, slow movement, and balance issues resurface, making activities challenging due to the nature of these times.

These motor fluctuations can significantly disrupt life by affecting work productivity and social engagement.

What Causes Motor Fluctuations?

The primary reason why motor fluctuations happen is the decrease in dopamine levels. It is a chemical that works as a reward for us doing any work. Its effect is even felt when we move, resulting in our body moving smoothly. But when a person has Parkinson’s, their brain cells can no longer make enough dopamine to allow them to smoothly do a task.

One interesting thing to note is that Parkinson’s disease attacks the tasks that we can do on autopilot, including walking, eating, or speaking. These are relatively simple tasks on which we have great control, and we do not have to spend tons of our brain power to achieve them. But with Parkinson’s disease knocking on the door, we start to lose control. However, with the use of drugs like levodopa, we can regain control to a certain degree.

Interestingly, as the disease progresses, our dopamine-producing brain cells start to die. It makes Parkinson’s medicine less effective, which lasts for a shorter time than earlier. In other words, our brain slowly and steadily reaches a point where it stops producing dopamine in large amounts, and we must rely on medicine to replace dopamine. So, why does this process occur? Researchers have presented two hypotheses for the same process. Let’s look at them:

  • With Parkinsonism becoming more aggressive, our cells start to lose the ability to synthesize dopamine. To overcome this dopamine scarcity, we use medicine like levodopa, which helps our brain cells release dopamine for about 60–90 minutes. This period is referred to as the “on” period. After the mentioned time, our body tends to remove levodopa from the system, and now cells do not have enough levodopa to produce dopamine. It leads to decreased dopamine levels and worsening of symptoms, also called “off” times.
  • Another reason that researchers have found is that our brain cells become more sensitive to both higher and lower concentrations. Yes, it is a conundrum that doctors have to find an optimal level for an individual. If the levodopa levels are too low, then there is a higher possibility that we will experience “off” periods. On the other hand, if levodopa levels are too high, it can lead to dyskinesis.

Now, what will happen is that the doctors will most likely increase your medication doses to achieve an optimal state of constant “on.” The goal is to maximize symptom control without increasing side effects.

Types of Motor Fluctuations

Here is a breakdown of the different types of motor fluctuations:

  • The on-off phenomenon is a classic “on-off” cycle where medication works well to control symptoms such as tremors and stiffness during “on” times. When it wears off during “off” periods the symptoms return. Some people may have unexpected “off” periods that are not related to medication.
  • Wearing off occurs when the effectiveness of levodopa, a Parkinson’s medication diminishes before the next dose is scheduled, leading to symptom recurrence.
  • Delayed “on” happens when it takes longer than usual for levodopa to start working and alleviate symptoms. This can be common after the first-morning dose, and meals rich in proteins can also make us more susceptible to this delay.
  • Partial “on” or dose failure occurs when taking medication does not fully improve symptoms or fails to bring any improvement at all (dose failure).
  • Freezing refers to an inability to move, often experienced while standing up, walking, or navigating spaces. It can last from seconds to minutes. It can also be accompanied by difficulty speaking or blinking. Freezing is more likely during “off” periods. We need to be extra careful with freezing, as it can increase the risk of falling.
  • Dyskinesia, or uncontrolled movements, can manifest as motions affecting a specific body part or the entire body. These movements are believed to occur when the brain becomes overly sensitive to levodopa over time, often occurring when dopamine levels peak, after medication intake.
  • Dystonia, or muscle contractions or spasms, is another symptom that can occur beyond our control. It causes our muscles to contract or tighten, which can last for a short time or many hours. The primary reason dystonia occurs is when levodopa levels wear off or when we first take the drug.

Non-motor fluctuations

Non-motor symptoms are another way that Parkinson’s manifests itself, and they can also experience “on-off” periods. There have been cases where mood swings are common and frequently accompanied by irritability, depression, or anxiety. In some cases, when the effectiveness of the medicine is going to decrease (“off” period), we can experience a high anxiety period. We can easily notice changes in our mood when we monitor the time when we take our PD medications and the occurrence of mood swings. The core reason for this is fluctuations in our brain’s dopamine levels.

Treating “On-off” fluctuations

There are three strategies that doctors use to help us cope with the “on-off” period.

  • Adjust Medicine Dose: Doctors might change the dose and timing of how often you take levodopa to avoid these dips in dopamine levels. It is done to deliver a constant level of dopamine-producing drugs to your brain.
  • Switch to New Drug or Delivery Method: If adjusting the levels and frequency of levodopa doesn’t show any improvements in dopamine, the doctors might suggest we try a long-acting form of levodopa. With this method, the drug is released with a steady dose of the medicine. It can be achieved using:
    • A patch that you wear on the skin
    • A capsule that steadily releases the drug into your body over several hours.
    • In some cases, a doctor might suggest taking levodopa gel which is introduced in our body through a needle in our stomach. It is a faster method to deliver dopamine-producing drugs into our bodies as the drug does not need to be metabolized.
  • Add Another Drug: To boost the effects of levodopa, doctors might prescribe a second medication. Once again the reason is the same, “to let levodopa work effectively.” It will allow us to stay away from “off” periods. Some drugs can allow our body to break down levodopa more slowly so our body can get more time with levodopa. A few drugs that are used include
    • COMT Inhibitors: These drugs work indirectly, extending the effect of levodopa by inhibiting its metabolism.
    • MAO-B Inhibitors: These drugs block the MAO-B enzyme, known to break down dopamine. It allows for the dopamine produced by our body to stay in the brain for a longer duration.


Dealing with motor fluctuations can be tough, for those living with Parkinson’s. But fret not there is reason to stay positive. Doctors have various Parkinson’s treatment strategies available to them, including tweaking medication dosages and schedules, changing medications that release steadily, or incorporating medications to complement levodopa. Through collaboration with doctors, we see Parkinson’s can discover ways to handle motor fluctuations and enjoy a more fulfilling life.

One question that might come to our mind is, is there a better alternative to the medication? Well, scientists have discovered that stem cells derived from the umbilical cord show promise in treating the condition. Many reported cases show that stem cell therapy for Parkinson’s disease effectively manages the condition and reduces the dose of drugs to be taken.

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