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The Ups and Downs of Dopamine: Impulse Control and Parkinson's
An Interview with Dr. Daniel Weintraub
For people with Parkinson’s disease (PD), managing the disease often comes down to a daily balance of dopamine — the neurotransmitter that is lost in PD. The challenge is to work with dopamine replacement therapies to find a balance between high and low levels.
Dopamine medications have improved life for millions of people worldwide. But now there is evidence that the vital neurotransmitter that eases PD symptoms can also work against them. Over the past 10 years, there has been increasing discussion in the PD community about impulse control disorders (ICDs), a phrase that is used to describe unhealthy levels of gambling, shopping, eating and sexual activity. Researchers think that some people with Parkinson’s who exhibit these behaviors may be experiencing a side effect of some of the dopamine replacement therapies used to treat Parkinson’s disease.
Are you concerned that you or a loved one may be affected? How can you identify these behaviors and talk to your doctor about them?
To answer these and other questions about ICDs, PDF News & Review (N&R) sat down with Daniel Weintraub, M.D., (DW) a Parkinson’s clinician and researcher from the University of Pennsylvania. Along with several of his colleagues, he compiled the largest study of ICDs ever conducted and the results appear in the May issue of Archives of Neurology.
N&R: What are impulse control disorders in Parkinson’s disease (PD)?
DW: In Parkinson’s, the term “impulse control disorders,” or ICDs, is commonly used to refer to a group of behaviors — gambling, shopping, eating and sexual behaviors — that are compulsive or impulsive in nature. While pathological gambling has been the main focus in PD, our report and other scientists have now demonstrated that all four are relatively common.
N&R: How common are ICDs among people with Parkinson’s?
DW: Our study demonstrated that, when measuring at one point in time, about 14 percent of people with PD experience one or more of the four behaviors mentioned above. We believe the true prevalence for these behaviors occurring anytime during PD may be higher — my personal guess is that it’s between 15 and 20 percent. Additionally, we found that if a person experienced one ICD, he or she had a 25–30 percent chance of experiencing two or more.
When we compared men and women, we found that both groups experience ICDs generally and compulsive gambling at similar rates. However, we found that men are more likely than women to have issues with sexual behavior, whereas women are more likely than men to experience compulsive buying and eating.
N&R: How do ICDs impact the lives of people with PD?
DW: There is a wide range. For some people, ICDs may be mild, or just a minor nuisance (for example, increased focus on eating sweets with a 10 pound weight gain). This group may be reluctant to make any changes to their PD medications because they value the medication’s benefits over relatively minor ICD symptoms.
For others, the impact of ICDs may be more severe. People who experience compulsive gambling and compulsive shopping may lose large sums of money, even to the point of bankruptcy. Those who binge eat may experience significant weight gain, causing discomfort and embarrassment and possibly increasing vascular disease risk factors. And some of those who experience compulsive sexual behaviors may begin engaging in unprotected sex or sex outside of an established relationship, placing themselves and others at risk physically and emotionally. ICDs typically impact not only the person living with PD, but also his or her loved ones.
N&R: Is it true that Parkinson’s medications cause ICDs? Can you explain why?
DW: We think that because people living with Parkinson’s so often have long-term exposure to dopamine replacement therapies, some may develop hypersensitivity. Hypersensitivity may in turn lead a person to “overreact” to medications. One common form of this overreaction is dyskinesia, the twisting and writhing movements that some people with PD experience. ICDs may be another example of how the body overreacts to a dopamine medication.
N&R: Which medications are linked to ICDs?
DW: The focus to date has been on two classes of medications — dopamine agonists, and levodopa, the gold-standard anti-PD medication that is usually taken as Sinemet®. In our recent study, my colleagues and I found that ICDs are most strongly associated with dopamine agonists. The two most commonly used by people with Parkinson’s, and which we studied, are pramipexole (Mirapex®) and ropinirole (Requip®).
We also found that ICDs were relatively common in people taking pergolide (Permax®), an agonist no longer prescribed in the United States. Our study suggested that levodopa may also be associated with ICDs. But the odds of having this problem are less likely with levodopa use than with use of dopamine agonists.
A less frequently used medication called amantadine (Symmetrel®), is under suspicion as well. However, some studies have suggested it may actually be effective as a treatment for pathological gambling in PD, so more research is needed.
N&R: Will a person develop an ICD immediately after beginning one of these medications?
DW: Sometimes a person will experience an ICD months after beginning a medication, but often there is a significant lag time of a year or more. My sense is that most people with an ICD know that something is different, but they may not see it as a significant problem or attribute the same importance to it as their loved ones will. For example, if a man experiences a higher than normal sex drive, he may think that it is still normal, but his wife may see it otherwise.
N&R: How do you treat ICDs?
DW: The most common treatment is to lower the dosage of or to remove the medication that has caused the problem, presumably the dopamine agonist. In mild to moderate cases, a person may elect to stay on his or her medications, but in moderate to severe cases, the doctor will feel obligated to take that person off of it completely.
N&R: Do ICDs disappear entirely when the medication is removed? How long does it take?
DW: My anecdotal answer is that ICDs “usually” subside for people who clearly did not experience the ICD previous to that time and developed it in the context of taking a dopamine replacement therapy for Parkinson’s. I have treated people who said they felt back to normal within a matter of days to a week, and others who said the change took weeks or months. There is a much smaller subset of people for whom ICDs persist despite the discontinuation of medications.
There is another subset of individuals for whom going off a medication is not an option. Perhaps their symptoms are too severe, or they’re receiving psychological benefit from the medication. Recent research suggests that some people may experience withdrawal symptoms when going off medications. I haven’t yet seen this in my own practice, but it’s something I now consider when removing medications from a regimen.
N&R: Are there additional treatments for those individuals?
DW: People who have significant motor fluctuations and have lived with PD for several years may be candidates for deep brain stimulation (DBS) surgery. Since a person can typically decrease his or her medications after DBS, this often will ease his or her ICD. A few other strategies have been explored, such as use of antidepressants, but there is little evidence at this point of their efficacy.
Scientists are also investigating novel treatments to resolve ICDs. My colleagues and I are studying an opioid antagonist called naltrexone. Other teams are studying a class of medications called glutamate antagonists, but the evidence on these strategies is limited at this point.
N&R: What does the future hold for diagnosing and treating ICDs in people with Parkinson’s?
DW: We hope the new compounds under investigation will help to treat ICDs, or that the newer dopamine replacement therapies may not have ICDs as a complication. In addition, I think we need to develop tools to improve diagnosis and care. I am a psychiatrist, so it is easy for me to discuss ICDs as part of every single visit, but not all people with Parkinson’s have access to a psychiatrist. Their neurologists may be saddled with many other issues to cover during an appointment.
In these cases, it would be helpful to develop screening instruments, such as surveys that can be self-completed by people with Parkinson’s and their families in the waiting room. These would provide the doctor with data that they might not have the time to gather during the visit. In 2009, we published a self-complete questionnaire called the QUIP in Movement Disorders. It takes less than five minutes to complete and is available for doctors to use in their clinical practice.
N&R: Should people with Parkinson’s be concerned about their risk of developing ICDs?
DW: I think they should be aware that these side effects exist and be attuned to any change in behavior, or pre-occupation with a new behavior. For example, increased Internet use (of gambling or adult websites) could be a sign of compulsive gambling or sexual behavior, but this doesn’t mean everyone using the Internet has a problem.
N&R: How can people living with Parkinson’s and their families bring up this topic with their doctors?
DW: I think clinicians have an obligation from day one, when they are prescribing dopamine replacement therapies, to let people know — not just about ICDs — but about the whole range of side effects that can occur with levodopa and dopamine agonists. This would include other non-motor effects, such as sleepiness and the potential to develop hallucinations.
I tell my patients that I want them and their families to be aware that a subset of people with Parkinson’s may experience changes in gambling, buying, eating and sexual behaviors. I encourage them to talk to me about any changes in behavior. Similarly, I would encourage all people with PD, along with their families, that if they have noticed any change in such behaviors, to bring this up immediately with their physicians.