Understanding On/Off Periods With Parkinson’s

Here’s why your Parkinson’s medications may not work consistently—and how to manage frustrating off periods when your motor symptoms ramp up.

by Lara DeSanto Health Writer

Finding the right combination and dosages of medications to help manage your Parkinson’s disease symptoms can be a challenge. Compounding that challenge is something called the “on-off” phenomenon, in which your meds start to wear off over time, leading to an increase in motor symptoms that can be difficult to deal with.

Keep reading to learn about the science behind this phenomenon, how “on” and “off” periods with your Parkinson’s medications may affect your symptoms, and how to manage this issue—including the latest treatment research.

The Role of Dopamine in Parkinson’s

Before we can really understand the on-off phenomenon of Parkinson’s medications, we have to first understand the role that dopamine, a neurotransmitter, plays in the body.

Normally, the brain makes its own dopamine, and it aids in several important functions throughout the body, explains Jennifer S. Hui, M.D., a neurologist with Keck Medicine of University of Southern California in Los Angeles, CA. “For unknown reasons, we have a loss of that neurotransmitter that leads to Parkinson’s disease,” she says. “That neurotransmitter helps with movement, and without it, movement is slowed down.”

That’s why common Parkinson’s symptoms include tremors, difficulty walking, and feelings of slowness or heaviness.

The role that dopamine—well, lack thereof—plays in Parkinson’s is evident in the main treatments for the medication. The gold standard for treating Parkinson’s is a drug called carbidopa/levodopa, says Dr. Hui. This drug, and several other medications for Parkinson’s (dopamine agonists), work by increasing dopamine in the brain to help reduce those motor complications.

What Are On and Off Periods With Parkinson’s Meds?

While you might expect that taking a medication on a consistent schedule would guarantee your symptoms would be kept at bay, that’s unfortunately not always the case with Parkinson’s disease—and that’s the core of the on-off phenomenon, says Ling Pan, M.D., clinical assistant professor of neurology and neurosurgery at NYU Langone Health in New York, NY.

The “on” period is when the medication is doing its job to prevent tremors and other motor symptoms, explains Dr. Hui. “Patients will often feel better fairly soon after taking their dose—even within half an hour,” she says. “It’s almost like a light switch is being switched on, and they can move a lot easier.”

That said, Dr. Hui explains, the effect can wear off over several hours—and that’s when you hit that “off” period. When you first start taking the drug, though, it’s normal to experience a honeymoon period, she says. “It may work all day, and you feel great, but overtime as the disease progresses, the medication doesn’t less as long, and off-time creeps in slowly and then becomes more noticeable and more regular overtime.” Typically, that’s when folks with Parkinson’s start to cycle between those on and off periods.

The Challenge of On and Off Periods

On and off periods with Parkinson’s medications can pose a significant—and frustrating—challenge when it comes to managing your symptoms, says Dr. Pan.

“On/off periods are a very relevant topic because it actually can cause a lot of disability in Parkinson’s,” she says. “Because when patients are on medications, they can almost feel like normal and do a lot of things, and once medications wear off, they are very disabled and immobilized at times.”

To address the issue, your doctor may have you start taking your medication dose more frequently—for example, switching from taking a pill every four hours to every three. “However, it becomes a logistical challenge of taking medications so often, and there are also risks of excessive dopamine,” she says. For example, non-motor symptoms of Parkinson’s—such as psychosis—become more likely the higher the dose of a dopamine agent you are taking. It becomes a difficult balance of trying to reduce motor symptoms with your medications without taking so much that you’re increasing other non-motor symptoms.

Thankfully, scientists have already worked to address this issue by developing new types of medications to help you manage those off-times, says Dr. Hui.

“For example, one is a sublingual apomorphine, which is a drug placed under the tongue and can kick you ‘on’ within 15 minutes. There’s also an inhaler form that works within 15-30 minutes,” she says. “These different delivery systems can help you maximize on-time quickly.”

Switching up your medications may also be helpful—for example, trying a dopamine agonist instead of levodopa may be a helpful option because they can assist in smoothing out motor fluctuations, says Dr. Pan.

Another option is to try one of several approved “add-on” medications designed to help minimize the effects of these off periods. For example, one was approved in just 2019 called istradefylline (Nourianz), which is used along with your main Parkinson’s meds to help improve those off times, per the NIH. “It can be effective at smoothing fluctuations,” says Dr. Pan.

If your health care team feels they have already maxed out on the medication route for managing off periods, there may be even further options to consider, such as deep brain stimulation, per the American Parkinson’s Disease Association.

“I subspecialize in deep brain stimulation with movement disorders, which is a surgical intervention that has been around for more than 30 years,” explains Dr. Pan. “Typically, we consider it at least four years after Parkinson’s diagnosis, and that’s around the time also that patients begin to experience motor fluctuations.”

Deep brain stimulation is when a surgeon implants a device within the part of your brain known to be affected in Parkinson’s—the basal ganglia—and acts almost like a pacemaker, she explains. “It’s like a pacemaker for a heart arrhythmia, which can be effective at regulating the rhythm. In Parkinson’s, it’s thought that there is abnormal firing of neurons in those areas of the brain, and by introducing this ‘pacemaker’ into those areas of the brain, it can help regulate the signal. It’s very effective in reducing the motor fluctuations in Parkinson’s patients.”

The Bottom Line on On/Off Periods With Parkinson’s Meds

Managing the cycling between on and off periods with Parkinson’s medications can be incredibly frustrating, but luckily, there are a number of effective ways to help reduce the peaks and valleys of motor symptoms.

Scientists are still exploring new and improved ways to help combat off periods with Parkinson’s drugs, according to the Michael J. Fox Foundation for Parkinson’s Research. You may even consider participating in one of these clinical trials, which you can learn more about with the Michael J. Fox Foundation’s clinical trial matching tool.

Even more exciting is the fact that researchers are also working diligently to try to improve Parkinson’s treatments in general—really looking into the crux of the disease to try to slow its progression overall, which would in turn help with this on-off period struggle, says Dr. Hui.

“There are a number of clinical trials going on, so I think we should also stay tuned for development of [new ways] to slow progression of disease,” she says.

Lara DeSanto
Meet Our Writer
Lara DeSanto

Lara is a former digital editor for HealthCentral, covering Sexual Health, Digestive Health, Head and Neck Cancer, and Gynecologic Cancers. She continues to contribute to HealthCentral while she works towards her masters in marriage and family therapy and art therapy. In a past life, she worked as the patient education editor at the American College of OB-GYNs and as a news writer/editor at WTOP.com.