Levodopa and Parkinson’s Disease

When prescribed, levodopa is extremely effective in treating the motor symptoms of Parkinson’s disease (PD) and is embraced by many with PD. Many individuals see using Levodopa as a vital ingredient in maintaining movement and quality of life. It is the most prescribed medication for PD and has been the mainstay of PD treatment for decades. APDA research support played a role in the discovery of levodopa for PD treatment when we funded the work of Dr. George C. Cotzias back in the 1960s.

Despite the research and general support from the Parkinson’s community, there are many myths that surround the use of levodopa that make many people hesitant to start taking it even after their doctor recommends it. To clarify some of the confusion and misinformation, APDA presents five myths that often circulate in the PD community about levodopa and tries to explain the reality behind them.

Note: In the US, the combination of carbidopa/levodopa is used in order for the levodopa to make its way to the brain before it breaks down, so you may often see the medication referred to in this way. Dosages appear as two numbers like 10/100, 25/100, and 25/250 — the first number refers to the milligrams of carbidopa in the pill. The second number refers to the milligrams of levodopa in the pill.

MYTH #1: It is important to delay starting levodopa for as long as possible to delay the onset of motor fluctuations and dyskinesias

FACTS: Early on in PD, a dose of levodopa can last six hours or longer, but often, as PD progresses, a levodopa dose tends to relieve symptoms for shorter amounts of time. A person may take a dose of levodopa and have good symptom relief for a period that is referred to as ON time. After this period is over, the effects of levodopa may start to wear off and symptoms of PD return for a different period referred to as OFF time. This phenomenon of alternating between ON and OFF time is known as motor fluctuations. In addition, dyskinesias or involuntary movements can occur, typically at the time of peak brain dopamine levels or when brain dopamine levels are changing. There are many strategies that your doctor can try to smooth out your response to medication throughout the day to help with motor fluctuations and dyskinesias.

The development of motor fluctuations and dyskinesias typically occurs after being on levodopa for many years. This has led some people to infer that the amount of time on levodopa influences the development of motor fluctuations and dyskinesias. If this were truly the case, it would make sense to delay taking levodopa for as long as possible.

However, it has been shown in many clinical trials that the onset of motor fluctuations and dyskinesias has to do with how long you’ve had the disease and not with how long you have been taking levodopa. If you wait until your disease has progressed before you start taking levodopa then motor fluctuations may start sooner after levodopa is started (because your disease is more advanced), as compared to when levodopa is started earlier in the disease progression (when symptoms are typically milder). Therefore, the development of motor fluctuations and dyskinesias is a function of the stage of Parkinson’s disease you are in and not the length of time you are on levodopa.

On the flipside: Levodopa does not have to be started as soon as you are diagnosed with PD. In general, there is no downside to postponing levodopa treatment if your PD symptoms are not affecting your daily function. However, please discuss with your neurologist or physical therapist to determine if you can exercise effectively and up to your maximal capabilities in your current state. Because exercise is potentially neuroprotective, you do not want to unnecessarily accelerate your PD progression by remaining off levodopa and not being able to exercise maximally.

MYTH #2: Levodopa loses effectiveness over time

FACTS: It is true that over time, people with PD tend to need to take more levodopa. As the progression of PD takes place, there are fewer dopaminergic neurons in the brain that can produce their own dopamine. A person with PD tends to need more medication containing dopamine to compensate for these changes. Therefore, a higher dosage of levodopa over time does not mean that the medication is no longer working; it means that the disease is changing.

In addition, as PD progresses, a person may start to develop more symptoms that are not responsive to levodopa. Levodopa best treats the motor symptoms of PD such as slowness, stiffness, and tremor. Some motor symptoms, including balance problems, do not respond as well to levodopa regardless of when the medication is started.

Non-motor symptoms that do not respond well to Levodopa, include:

• fatigue
• depression
• sleep problems
• cognitive difficulties
• variations in blood pressure
• urinary problems
• constipation

These symptoms do not typically respond to levodopa and may cause more disability over time than motor problems. The perception may be that over time, levodopa is not effective, when in fact there are new symptoms that develop that levodopa cannot treat.

MYTH #3: Taking levodopa should be avoided if possible. Taking a natural medication, like Mucuna, is better

FACTS:  Levodopa can be life-altering for people with PD, helping them move more naturally and restoring quality of life. Mucuna (also known as the velvet bean), contains 6-9% levodopa on average by weight, so taking Mucuna is a method of ingesting the same compound, levodopa. However, Mucuna has several limitations which make it difficult to be the sole medication used for PD symptoms without any pharmaceutical-grade levodopa. Most importantly, it does not contain carbidopa, an enzyme inhibitor that is incorporated into the pharmaceutical form of levodopa, which stops the breakdown of levodopa in the bloodstream. Adding carbidopa or an equivalent compound to levodopa was a major scientific breakthrough, allowing for much less levodopa to be ingested, since more passes into the brain where it is converted into dopamine. With lower doses of levodopa ingested, the side effect profile of levodopa, especially nausea, is substantially improved. Mucuna does not contain carbidopa, so the amount of levodopa that can be ingested without side effects is limited. In addition, Mucuna is not regulated by the Food and Drug Administration, so the amount of levodopa in a supply of Mucuna is unreliable leading to doses becoming unpredictable.

On the flipside:  There are people with PD who have successfully incorporated Mucuna into their standard levodopa regimen with good effect. If you are having trouble with your levodopa regimen, and you are interested in trying Mucuna, speak with your neurologist about the best way forward.

MYTH #4: Levodopa causes intolerable side effects for many people

FACTS: Levodopa can have an array of side effects such as nausea, fatigue, dizziness, and hallucinations. However,  with patience, you and your neurologist will likely be able to find a formulation and dose of levodopa that you will be able to tolerate and can help treat your PD symptoms successfully. Occasionally, your neurologist will need to prescribe an additional medication to treat a side effect from levodopa. Sometimes, anxiety over a possible inability to tolerate levodopa interferes with being able to tolerate the medic]ation. In these cases, treating the underlying anxiety can be helpful.

Dyskinesias are a common side effect of levodopa. Like any side effect of a medication, dyskinesias exist on a spectrum. Sometimes dyskinesias are very mild and can be barely noticed by the person with PD. Other times, dyskinesias are severe and can cause imbalance or social embarrassment. In most cases, dyskinesias are in the middle of the spectrum. Your neurologist will work together with you to find the formulation and dosing schedule of levodopa that minimizes dyskinesias. If this is not sufficient, medications to decrease dyskinesias can be prescribed as well.

On the flipside: A small number of people have significant side effects from one or more formulations of levodopa to the point that taking the medication reduces their quality of life. This occurs most commonly with the immediate-release version, also known as Sinemet. If this occurs, talk with your doctor about what can be done. As mentioned above, there are ways to considerably improve the tolerance of levodopa, such as by slowly titrating the medication up over time or taking the medication with certain foods. Changing the formulation to a longer-acting version can substantially improve the situation as well. With these changes, those affected can obtain the benefits of levodopa without having distressing side effects.   Nevertheless, most movement disorders neurologists have encountered a small number of patients who seem unable to tolerate any formulation of levodopa regardless of what is tried.  This is a rare, but difficult problem to face because levodopa is the most effective medication for the motor symptoms of PD. If it can’t be tolerated, other medications for PD can be tried in its place, but they are unlikely to give as robust relief of PD motor symptoms as levodopa provides.

MYTH #5: Levodopa is toxic to neurons and contributes to disease progression

FACTS: The question of whether levodopa is toxic to neurons and accelerates disease progression has been studied in numerous ways over the past three decades, without conclusive evidence that it does so. In fact, levodopa has been shown to increase life expectancy in people with PD, which strongly argues that levodopa does not accelerate the disease.  In addition, levodopa has been shown in clinical trials to improve quality of life for people with PD.

In summary, the effectiveness of levodopa is unparalleled for people with PD, and as such, it is important to understand the facts about the medication and not get confused or deterred by common myths that could keep you from benefitting from this treatment. Always talk to your doctor openly about any concerns or questions you have so together you can make an informed decision that best suits your personal situation.

 Tips and Takeaways

• Levodopa is the mainstay medication of PD treatment, yet there are many misperceptions and myths surrounding this medication.
• Development of motor fluctuations and dyskinesias are a function of the stage of Parkinson’s disease you are in and not the length of time you are on levodopa.
• Needing more levodopa over time does not mean that the medication is no longer working; it means that the disease is changing.
• With patience, you and your neurologist will likely be able to find a formulation and dose of levodopa that you will be able to tolerate and will treat your PD symptoms successfully.
• Levodopa has been shown to increase life expectancy in people with PD, which strongly argues that levodopa does not accelerate the disease.
• As always, be sure to talk with your doctor about any medication questions or concerns, or any side effects you are experiencing.