Although there’s no cure for Parkinson’s Disease (PD), it’s not a death sentence. Despite the tremors, rigidity, fatigue and a potentially dramatic cycle of on and off periods in which one’s ability to move with ease is greatly affected, it is possible to live a fairly normal life — with the right medication.
James Morgan, a partner at global law firm Squire Patton Boggs, speaks for many people with PD when he says, “I would be nonfunctional without the drugs.”
Patients have found medications for Parkinson’s to be effective in easing symptoms, but the 2 main drugs prescribed to treat Parkinson’s disease — levodopa (brands include Sinemet and Sarcopa) and dopamine agonists — cause some surprising side effects.
Although drugs play a major role in reducing symptoms and enabling people to improve their quality of life, it’s worth being cognizant of the sometimes debilitating toll they can take. Levodopa can cause dyskinesia, hallucinations and even psychosis. And the side effects of dopamine agonists rank as unexpectedly bizarre. Impulse control disorders such as hypersexuality, gambling, binge eating and excessive shopping show up in between 17% to 20% of those undergoing dopamine agonist treatment, according to Daniel Weintraub, MD, associate professor of Psychiatry and Neurology at the Perelman School of Medicine at the University of Pennsylvania and an author of a study published in JAMA Neurology. Dopamine agonists can have very severe withdrawal symptoms, to the point that some people, desperate to stop taking these drugs, have undergone brain surgery to help withdrawal.
In this article, we focus on what PD is and the side effects of levodopa. Part 2 weighs the pros and cons of dopamine agonists.
A Brief Description of PD
Currently, at least 1 million people in the US and an estimated 10 million worldwide live with Parkinson’s, making it the second most common neurodegenerative disorder (Alzheimer’s ranks first). Parkinson’s disease, a disorder of the central nervous system, is caused by a degeneration of nerve cells in certain parts of the brain that produce a neurotransmitter called dopamine. Dopamine, commonly known for its role in controlling the brain’s reward and pleasure center, is partly responsible for starting a circuit of messages that coordinate normal movement.
In the absence (or with substantial reduction, more than 80% of the normal level) of dopamine, the neurons — called dopamine receptors — in the brain’s striatum are not adequately stimulated. In simple language, as a person’s brain slowly stops producing dopamine, a person has less and less ability to regulate his or her movements, body and emotions. The result is impaired movement with tremors, slowness, stiffness or balance problems. Lesser known symptoms include depression, apathy and dementia.
A new theory, called Braak’s hypothesis, hints at the possibility of new breakthroughs for treating PD. The theory suggests that the earliest signs of Parkinson’s may be nonmotor symptoms such as the loss of smell, sleep disorders and constipation. These symptoms may be serious red flags that precede motor features by several years. The new vanguard of PD research is increasingly focused on these “nonmotor” symptoms to both detect PD as early as possible and to look for ways to stop its progression.
The Two Most Common PD Drugs
Dopamine replacement (Levodopa, carbidopa-levodopa, Sinemet): The main drug used to treat PD symptoms, levodopa is chemically very similar to the body’s natural neurotransmitter. The drug, which is taken by mouth, enables the brain’s basal ganglia to convert levodopa to dopamine — meaning levodopa acts like dopamine in the brain’s movement centers. Levodopa can produce dramatic results, especially in reducing rigidity and tremors and improving movement. It’s generally taken in combination with carbidopa, which keeps the levodopa from being broken down in the digestive tract before it reaches the brain. It also permits a lower dose of levodopa and reduces side effects, which can include nausea and facial flushing (a sense of heat in the face, somewhat akin to a hot flash). Two new extended-release carbidopa-levodopa drugs were just approved this year: Duopa, an oral medication approved for some patients in the later stages of Parkinson’s, and Rytary. In a clinical trial, users of Rytary reported that their amount of “off time” improved by more than an hour a day.
Dopamine agonists (Mirapex, Requip, Neupro): These drugs stimulate the dopamine receptors in the brain and mimic the effects of dopamine, compensating for the depletion of the neurotransmitter. Typically, dopamine agonists are often prescribed for younger patients who are in the early stages of the disease to delay the need for levodopa — and thus the eventual “on-off” syndrome (and unpredictable fluctuations in symptoms) that occurs after taking it for years. The need for delaying levodopa has been questioned, however. (Part 2 of this article, to be published on July 2, will focus on controversy regarding dopamine agonists.)
Howard Weiss, MD, director of the Parkinson’s Disease and Movement Disorder Programs at the LifeBridge Health Brain & Spine Institute in Baltimore, says the approach of delaying levodopa was fueled by a phobia, a scare that started more than 2 decades ago, based on the belief that levodopa accelerated disease progression.
“It’s no longer accurate,” he says. Dopamine agonists are also used in combination with levodopa when the effectiveness of levodopa treatment wanes and a higher dosage induces side effects.
Shakedown: Side Effects of Levodopa
Hallucinations and psychosis are a side effect of levodopa. They tend to manifest as disturbances of perception (seeing people or things that aren’t really there) as opposed to sound. According to a report published last year in Psychiatric Times, Management of Psychosis in Parkinson Disease by Dr. Weiss and Sam Adler, MD, “After having Parkinson’s for many years, benign hallucinations occur in approximately 10% to 20% of nondemented patients with PD who receive dopaminergic treatments.”
Christopher Hess, MD, assistant professor of Neurology at the University of Florida Center for Movement Disorders and Neurorestoration, says that “after having Parkinson’s for many years, some people feel like there is a presence in the house [when there is no one].” Or it may be a passage hallucination, which Hess describes as “fleeting images in the corner of the eye.”
As dependence on levodopa progresses, visual hallucinations in direct vision occur. If the hallucinations are mild, says Dr. Hess, patients can stay on levodopa. But in rare cases, the hallucinatory experiences become increasingly vivid and frightening — that’s when the symptoms evolve into psychosis. Suspicions of harmful plots, spousal infidelity and financial impropriety are a common cluster of delusions encountered in patients with psychosis. In those cases, more monitoring is required, as well as a change in medication or dosage.
“Typically, you need to hospitalize a patient till they are stabilized,” Dr. Hess says.
Because the disease acts like a moving target, medication and dosage might change constantly. Regarding hallucinations, Dr. Hess points out, “This doesn’t happen to everybody or in the same degree. It’s something you deal with and there are other medications that can help.”
Most of the hallucinations remain benign, but because the potential for psychosis exists, clinicians should be extra cautious and vigilant when increasing dopaminergic dosage or adding new medications. To make this situation even more challenging, many patients may not readily admit to hallucinations for fear of being perceived as crazy. Not only do clinicians have to be proactively inquisitive — it’s important for patients to adopt a policy of full disclosure.
After taking levodopa drugs for 5 years or more, many people find that the effectiveness begins to wane. More than half suffer “on-off syndrome,” a cycle of medication-induced motor fluctuations. “Off” times are a state of decreased mobility and “on” times are when the medication is working and symptoms are controlled.
Motor fluctuations usually happen when levodopa is waning. The effects of wearing off can happen surprisingly quickly. That’s why the timing of taking medications is so important. Morgan says, “You have to be religious about sticking with your meds, because they don’t work unless you are on top of it.”
Involuntary movements (dyskinesia)
Involuntary movements are often mistaken for a symptom, but in fact they are a side effect of Parkinson’s medicine. According to the Michael J. Fox Foundation, “Some patients report dyskinesia to be as debilitating as the disease itself.”
After many years of levodopa treatment, dyskinesia — muscle movements that can’t be controlled — may set in. They can include twitches, jerks, twisting or writhing movements, or restlessness. Because Parkinson’s is such an unpredictable disease, when and how often dyskinesia appears can be different for each person it affects. It might mean involuntary movements occur throughout most of the day, or it might be limited to brief spurts after taking medication or just before the next dose is due.
Despite the side effects, levodopa remains the gold standard of PD treatment. “People are less levodopa-phobic than they used to be,” says Dr. Weintraub. For many, the controversies that surround dopamine agonists, which used to be the first line of defense against Parkinson’s, mean they have lost some of their luster. The shift signifies levodopa’s return to dominance.
“Although it’s no angel when it comes to side effects,” says Dr. Weiss, “it’s much more effective, less expensive, and has fewer side effects [than dopamine agonists]. That’s a good trifecta.”
As with any Parkinson’s medication, the biggest takeaway regarding levodopa is that close monitoring is essential.
“It’s a constant testing and retesting and reconfiguring the formula. It’s not static,” says Morgan. “You really have to talk to your doctor, so find someone you can relate to. Talk to him every time about what’s happening.” When the lines of communication are open, the probability of adjusting to Parkinson’s successfully become much higher.
- The End for Levodopa Phobia (National Parkinson Foundation)
- Stronger Warnings Urged for Drugs Linked to Impulse Control Disorders (Parkinson’s Disease Foundation)
- Management of Psychosis in Parkinson Disease (Psychiatric Times)
- Parkinson’s Disease Handbook pdf (American Parkinson’s Disease Associates Inc.)
- Depression, anxiety, and psychosis in Parkinson’s disease (BC Medical Journal)