When you first begin taking Parkinson’s medications, you may find that they work so well that you rarely or never experience troublesome symptoms. As time passes, however, you may notice that your medications don’t control your symptoms for as well or for as long as they once did. When this happens, it is time to talk with your care team about your treatment goals and possible modifications to your treatment plan.
While there are multiple ways your plan might be modified, this post focuses on four possible changes to your medications, including add-on therapies, controlled-release and extended-release formulations, advanced therapies, and on-demand options.
WHEN TO MODIFY YOUR TREATMENT PLAN
Parkinson’s experts often say that the best time to begin Parkinson’s medications is when your symptoms start negatively impacting your quality of life. The same is true when it comes to modifying your treatment plan: if the medications you take no longer adequately manage your symptoms, talk to your care team about additional options.
In addition to new symptoms, symptom fluctuations, and medication side effects that lower your quality of life, other reasons to talk with your care team about changing your treatment plan include:
INCREASING OFF TIME
As Parkinson’s progresses and your brain cells produce less dopamine, you may begin to experience more OFF times–periods when your medications aren’t working optimally and your symptoms return.
There are a number of lifestyle choices you can take to minimize OFF times. These include paying attention to your protein and water consumption, adding fiber to your diet to manage constipation, making sure you get adequate exercise. However, if you reach the point where these things are not enough to manage OFF times, it’s a good time to talk with your care team.
MEDICATION ADHERENCE CONCERNS
You may need to explore modifications to your treatment regimen if you are having trouble with medication adherence. Medication adherence refers to how precisely you follow the medication-related details of your treatment plan.
People with Parkinson’s often find it hard to take their medications on time. This can happen for a variety of reasons: high “pill burden” (meaning you take several different medications and/or several different doses each day), desire to avoid side effects like dyskinesia, mood and cognition issues, neuropsychiatric issues, and more. Some medications last longer and can decrease the amount of doses you have to take each day.
LEVODOPA-INDUCED DYSKINESIA
Levodopa-induced dyskinesia is uncontrolled jerking, dance-like, or wriggling movements. In people with Parkinson’s, the biggest risk factor for dyskinesia is a greater number of years of living with the disease. The second biggest risk factor is a higher dose of levodopa.
Dyskinesia most commonly occurs when medications are at their peak effect, which is often about an hour after you take the medication. There is also a less common pattern, known as “wearing-off dyskinesia.” This is when dyskinesia occurs as a dose of medication wears off. Some of the treatment options and strategies described below may help if you are experiencing dyskinesia.
COMMON TREATMENT MODIFICATION STRATEGIES
There are three main ways you can modify your medication regimen: you can use a controlled-release or extended-release formulation, you can add-on an additional medication to your regimen, or you can pursue an advanced therapy. If you are experiencing unpredictable OFF periods or doses that fail to take effect, you might also add a “rescue” therapy.
Controlled-release and extended-release formulations extend how long each dose of medication remains effective. Add-on therapies are treatments used alongside other “first-line” Parkinson’s medications (like carbidopa/levodopa and dopamine agonists) to improve some aspect of your symptom management. Extended-release and add-on therapies are often used for similar purposes—managing OFF times and motor fluctuations—but each approach has its own possible benefits and downsides.
CONTROLLED-RELEASE AND EXTENDED-RELEASE CARBIDOPA/LEVODOPA FORMULATIONS
OVERVIEW
Levodopa helps with Parkinson’s symptoms by essentially replacing the dopamine that is lost due to Parkinson’s.
There are multiple carbidopa/levodopa formulations. Some are immediate-release, and each immediate-release dose remains effective for a relatively short period of time. This short effective window and the fact that Parkinson’s is progressive mean that, over time, more and more doses are needed to adequately manage symptoms. This frequent dosing can lead to a variety of difficulties, including ON/OFF fluctuations and dyskinesia.
Controlled-release carbidopa/levodopa and extended-release carbidopa/levodopa can help decrease the number of medication doses you take. Extended-release formulations may convey other benefits, as well.
If immediate-release carbidopa/levodopa treatment helps you manage your symptoms but frequent dosing is causing difficulties, talk with your care team about whether one of the formulations below might be right for you.
CONTROLLED-RELEASE CARBIDOPA/LEVODOPA
This formulation was approved in 2011 as Sinemet CR. Since 2019, it has been available only as a generic medication. This formulation may allow you to take less frequent doses because each dose may remain effective somewhat longer than a dose of immediate-release carbidopa/levodopa. However, due to the way the tablets are produced, controlled-release carbidopa/levodopa often takes longer than immediate-release carbidopa/levodopa to take effect.
EXTENDED-RELEASE CARBIDOPA/LEVODOPA FORMULATIONS
Many people find that extended-release formulations offer a significant advantage of controlled-release carbidopa/levodopa: extended-release formulations may significantly improve management of motor symptom fluctuations and dyskinesia while also decreasing the overall number of pills you take.
These treatments tend to be more expensive than generic immediate-release or controlled-release formulations of carbidopa/levodopa, and extended-release therapies may not be covered by every insurance plan.
CREXONT®
CREXONT is a new Parkinson’s medication that was approved by the FDA in August 2024, and it is currently the longest-lasting formulation of oral carbidopa/levodopa. CREXONT combines extended-release pellets and immediate-release granules of carbidopa/levodopa to provide more “good ON” time each day with fewer daily doses and less troublesome dyskinesia compared to immediate-release carbidopa/levodopa. Visit our blog post about CREXONT for more information.
RYTARY®.
RYTARY was the first extended-release carbidopa/levodopa formulation. RYTARY capsules contain beads of carbidopa-levodopa that are absorbed at different rates. Some beads are absorbed at the same rate as immediate-release carbidopa/levodopa, while others are absorbed more slowly. Rytary allows some people to have more “good ON” time and less troublesome dyskinesia with fewer doses per day compared to immediate-release carbidopa/levodopa.
EXTENDED-RELEASE DOPAMINE AGONIST FORMULATIONS
Dopamine agonists function similarly to carbidopa/levodopa: they essentially replace the dopamine lost due to Parkinson’s.
While dopamine agonists are similar in function to carbidopa/levodopa, they may cause a greater variety of side effects, some of which—like impulse control disorders—can be serious. When you visit with your care team, discuss any possible side effects of any medications you take or are considering taking.
There are three extended-release dopamine agonist formulations:
EXTENDED-RELEASE PRAMIPEXOLE
Pramipexole can be used alone or with other medications to treat Parkinson’s motor symptoms. Studies show that extended-release pramipexole significantly improved Unified Parkinson’s Disease Rating Scale (UPDRS) scores and OFF times compared with a placebo. MIRAPEX ER® is a brand name extended-release pramipexole medication.
EXTENDED-RELEASE ROPINIROLE
Ropinirole is another treatment approved as monotherapy and as an adjunct to levodopa in the treatment of Parkinson’s. Requip® is a brand name extended-release ropinirole medication.
NEUPRO® ROTIGOTINE PATCH
The Neupro patch delivers through the dopamine agonist rotigotine through the skin via an adhesive patch. This transdermal system delivers a steady supply of the medication for 24 hours. Rotigotine is approved for use as a monotherapy and as an add-on therapy. Because rotigotine provides a steady supply of medication, it can help with multiple complicated Parkinson’s symptoms. Although there are several possible side effects, rotigotine’s ease of use and unique, transdermal delivery system make it a valuable treatment option, especially for those who have difficulty taking doses on time.
ADD-ON THERAPIES
Like extended-release formulations, add-on therapies may extend how long your doses are effective and help you manage motor complications. Add-on therapies may also allow you to address a specific issue. For example, MAO-B inhibitors may help with some mood-related symptoms of Parkinson’s. A possible downside to add-on therapies is that they require you to manage more medications. This can increase possible side effects and make it harder to take the treatments on time.
ADENOSINE RECEPTOR ANTAGONISTS
Adenosine receptor antagonists act to block the receptor sites for the neurotransmitter adenosine, which acts as a central nervous system depressant. This class of medication is approved for use in conjunction with carbidopa/levodopa to help reduce OFF time.
Adenosine receptor antagonists can increase ON time without troublesome dyskinesias for many people, but each person’s experience may vary, as dyskinesias are a commonly reported side effect of adenosine receptor antagonists.
AMANTADINE HYDROCHLORIDE
Amantadine can be used alone or as an add-on treatment for slowness, stiffness, and tremor. Amantadine may help improve motor symptoms while also reducing dyskinesia, but there are multiple possible side effects that require careful monitoring, including confusion, constipation, and light-headedness. There are also extended-release formulations of amantadine available.
COMT INHIBITORS
Catechol-o-methyl transferase inhibitors (COMT inhibitors) block levodopa metabolism and prolong each levodopa dose’s effects. COMT inhibitors have no effect on their own and are always used in conjunction with levodopa. COMT inhibitors are used primarily to treat motor fluctuations and reduce OFF time. Because COMT inhibitors increase and prolong the effects of levodopa, the side effects of levodopa may also be enhanced, including dyskinesia.
Current options for COMT inhibitors that are approved for Parkinson’s include:
Entacapone is available as standalone treatment, but it is also available in a single tablet that also contains carbidopa/levodopa. This combined form is available in multiple strengths in generic and branded options. The brand name is Stalevo. Note that each dose of Stalevo may take longer than other immediate-release formulations and extended-release formulations to reach maximum concentration in the body. Possible side effects of entacapone include diarrhea and discolored urine and/or sweat.
ONGENTYS is the brand name of opicapone. It is only available as a branded medication. By blocking the COMT enzyme, ONGENTYS helps reduce OFF time by keeping levodopa levels steady longer.
MAO-B INHIBITORS
Rasagiline and selegiline are selective MAO-B inhibitors that can be taken as a once-daily monotherapy or as an add-on to extend the efficacy of a dose of levodopa. Safinamide is another MAO-B inhibitor for Parkinson’s, it is approved for use only as an add-on therapy.
We have discussed each of these treatments in separate blog posts: rasagiline, selegiline, safinamide.
SURGICAL AND ADVANCED THERAPIES
Another approach to managing advancing symptoms of Parkinson’s is to consider an advanced therapy. These include DBS; Duopa; focused ultrasound (FUS); and VYALEV, a recently approved formulation of carbidopa/levodopa designed for 24-hour continuous infusion. Each of these treatments has advantages and risks and are considerably more complicated to begin using than the controlled-release, extended-release, or add-on options described above.
Depending on your circumstances, you and your care team might decide that one of these options is preferrable to altering your medication regimen, but many people try altering their medication regimen using a controlled-release formulation, extended-release formulation, or an add-on therapy first since these are usually easier to start, modify, and stop using than an advanced therapy.
RESCUE THERAPIES
In addition to the treatments above, there are two on-demand, “rescue” therapies available in the United States to help manage complex ON/OFF fluctuation, Apokyn and Inbrija.
These treatments are intended to be taken at the first sign of an OFF period to help you quickly return to an ON state.
FINDING THE RIGHT MODIFICATIONS FOR YOU
Above, we have described multiple ways you and your care team can modify your treatment plan when your medications are no longer managing your symptoms.
There are many ways to optimize your Parkinson’s treatment, and as evidenced by the fact that two significant new treatments were approved in 2024, the list of available options for your individual needs continues to grow.
Make the most of these developments, and remember that everyone’s experience of Parkinson’s changes over time. What worked for you in the past may not be the best option for today. When the impacts of your symptoms change, talk with your care team to see whether they’d recommend any medication-based changes to could help you improve your symptom management so you can live well today.
ADDITIONAL RESOURCES
Parkinson’s Treatment and Therapy Resources
Onset and Duration of Effect of Extended-Release Carbidopa-Levodopa in Advanced Parkinson’s Disease
Thank you to our 2024 Peak Partners, Amneal and Mitsubishi Tanabe Pharmaceuticals for supporting our blog content in 2024.
