Episode 135: Feeling Nausea with Parkinson’s

Dan Keller 0:02 Welcome to this episode of Substantial Matters: Life and Science of Parkinson's. I'm your host, Dan Keller, at the Parkinson's Foundation. We want all people with Parkinson's and their families to get the care and support they need. Better care starts with better research and leads to better lives. In this podcast series, we highlight the fruits of that research, the treatments and techniques that can help you live a better life now, as well as research that can bring a better tomorrow.

Motor symptoms such as stiffness, slowness of movement, and tremor are hallmarks of Parkinson's disease, and can often be controlled with levodopa or other similarly acting medications, but non-motor symptoms can be just as or more troubling to a person with Parkinson's. An example is feeling nausea with Parkinson's, which can result from the disease itself or be related to anti-Parkinson's medications. When I spoke with Dr. Andrew Feigin of New York University Langone Health in New York City, he told me about the causes of nausea, medical and non-medical ways to help alleviate it, and just how prevalent it is.

Dr. Andrew Feigin 1:29 Nausea is quite common in Parkinson's disease. If you look at, you know, during the course of a person's Parkinson's disease, how likely are they to, at some point, experience nausea? I'd say probably more than 50% of people experience nausea at some point, either due to the Parkinson's disease, and we could talk a little bit more about that, or due to side effects of medication.

Dan Keller 1:50 Are there any people who are particularly affected? Can you figure out who's most at risk, or is it pretty random?

Dr. Andrew Feigin 1:56 I think it's mostly pretty random, actually, to be honest. The underlying cause in some people with Parkinson's disease who have nausea is a problem called gastroparesis, which essentially means poor emptying of the stomach, and who that affects, why that affects some patients with Parkinson's disease more than others, I think is hard to predict, and just some people are affected, some people quite severely affected by it. I've seen patients who had a significant enough gastroparesis, or incomplete emptying, or slow emptying of the stomach, to the point where they had no appetite, lost weight, became dehydrated, and others seem to not have that as a symptom at all. And it's hard to predict who will be afflicted with this and who won't.

Dan Keller 2:40 Does that also affect absorption of medication, any oral medication?

Dr. Andrew Feigin 2:45 It does. Yeah, so sometimes people with Parkinson's disease can have what are called delayed-ons or dose failures when they take their levodopa. They take their medication, and you know many people, it's very predictable, they take their levodopa in particular, and it kicks in after 15 to 30 minutes, and lasts a certain number of hours, and then wears off. Some people, it doesn't kick in in a predictable way, and oftentimes the reason for that is that the medication is not passing from the stomach to the first part of the small intestine, which is where levodopa gets absorbed in a regular predictable way.

Dan Keller 3:20 Right? So it's sort of stuck before it ever gets absorbed. Are there other common causes of nausea in PD, the medication itself, or food, or any activities?

Dr. Andrew Feigin 3:31 I'd say the other main cause of nausea, maybe the most common cause of nausea in patients with Parkinson's disease, is the gold standard therapy for Parkinson's disease, levodopa. When people take levodopa, levodopa is converted to dopamine by an enzyme called dopa decarboxylase, and that can happen before the levodopa gets into the brain. So, levodopa is always given with another medication called carbidopa in a combined pill, sometimes referred to as Sinemet, because the old brand name of the drug carbidopa is there not to treat the Parkinson's disease. The carbidopa is there to block this enzyme, dopa decarboxylase, from converting levodopa to dopamine before it gets into the brain. If levodopa is converted to dopamine before it gets into the brain, it can cause quite a few side effects, one of which is it can bind to dopamine receptors in the stomach and in the intestines and can cause nausea.

Dan Keller 4:22 I guess that's the origin of the name Sinemet—sin without in Latin, met emesis, nausea. So, why doesn't it work? Is it that they're both being delivered at the same time? If carbidopa got there before the levodopa, would it work better?

Dr. Andrew Feigin 4:39 It turns out that we say that the average adult person needs a minimum of 75 milligrams of carbidopa to block peripheral dopa decarboxylase, but that's very variable from person to person. Some people require more carbidopa than that, and some people require less. So I think that when somebody's starting carbidopa/levodopa for the first time—first of all, we tend to start at low doses. We tell them to take half a pill twice a day for a week, half a pill three times a day for some period of time, and then go up to a whole pill three times a day. If you take a whole pill of 25/100 carbidopa/levodopa three times a day, you get that 75 milligrams per day of carbidopa. But if you're starting with a half a pill twice a day, and half a pill three times a day, you're not quite at that kind of average amount of carbidopa that you need to block peripheral dopa decarboxylase.

So you know, for many people, the amount of carbidopa that they're getting with their levodopa is not sufficient. So, kind of getting ahead of myself, because usually when people feel nauseous from taking levodopa, we do kind of non-medical adjustments, like telling people to take their medication with food or with more water, and often that's effective for helping the nausea. But sometimes if we do choose to treat it medically, we will give people extra carbidopa. So you can take pure carbidopa. We can prescribe what's called Lodosyn, or it's the brand name for just pure carbidopa, and you can take an extra 25 milligrams of carbidopa with each dose of carbidopa/levodopa, and that can be sufficient for ameliorating the nausea for some people.

Dan Keller 6:11 So, is the nausea really originating in the gut? I mean, there are central brain mechanisms which make you feel nauseous, but is it really because the levodopa is acting in the gut?

Dr. Andrew Feigin 6:22 I think it's probably actually the action of levodopa at these peripheral receptors is being conveyed to some central mechanisms that are causing the nausea. I don't think it's the actual gut that's causing the nausea, although it is possible that that may be contributing. Yeah.

Dan Keller 6:36 You described that there is medication, so you can get more carbidopa to block the levodopa in the gut. Are there other ways that it's treated? I think you said behavioral changes and things like that, but how effective are those, and what else might there be to do about it?

Dr. Andrew Feigin 6:51 I think taking the carbidopa/levodopa with food is quite effective. I'd say that helps a lot of people who have problems taking low doses of carbidopa/levodopa, and then adding extra carbidopa is also quite effective for those whom the dietary changes don't really seem to make much of a difference. Adding extra carbidopa can also be helpful, and then finally there are other medical treatments.

There's a drug called Domperidone, which is not FDA approved, not available by prescription in the United States, but is available by prescription from Canada or from Europe, and that medication blocks dopamine receptors in the GI tract, does not cross the blood-brain barrier, so it doesn't block dopamine in the brain. We wouldn't want to give a drug that blocked dopamine in the brain to somebody with Parkinson's disease, for obvious reasons. People with Parkinson's have too little dopamine to begin with, if you give them a drug that blocks dopamine in the brain, you're going to make them worse. But this particular drug, Domperidone, blocks dopamine only peripherally and doesn't get across the blood-brain barrier, and so that drug can be very effective in blocking some of the peripheral side effects of dopamine, or levodopa converted to dopamine, and sometimes we do resort to that. There are some risks associated with Domperidone in that there have been reports of people with increased risks of cardiac arrhythmias and other cardiac problems, and so you know, when we do do that, we have to do it with some level of caution.

Dan Keller 8:15 Do the drugs that are approved in the US that are often used for nausea interfere with dopamine, things like ondansetron and things like that, or are they effective here?

Dr. Andrew Feigin 8:26 You could use typical antiemetics. We do on occasion, and those drugs are used in particular, actually, one of the drugs that we use for Parkinson's disease that very commonly causes nausea is a drug called Apomorphine, which is a potent dopamine agonist, and probably the mechanism by which it causes nausea is similar to how levodopa being converted to dopamine causes nausea, and so treatment with apomorphine requires pre-treatment with an antiemetic, an anti-nausea drug, like you mentioned, actually.

Dan Keller 8:53 But don't people use that as sort of a rescue medication for off periods? So, do they get nauseous when they inject that?

Dr. Andrew Feigin 8:59 Well, they have to pre-medicate with one of these drugs, either as an injection or it's now available as sublingual, and even so, you still need to pre-medicate with an antiemetic.

Dan Keller 9:09 How long does the nausea last? Does it actually interfere with them eating something and they get deficient in calories, or does it pass and they can then eat regularly?

Dr. Andrew Feigin 9:20 So the nausea that is associated with gastroparesis in some patients with Parkinson's disease, it can vary in severity. It can be mild nausea now and then that doesn't seem to have an impact on their weight. I have seen patients with Parkinson's disease who became almost cachectic because of this feeling of fullness in their stomach, always, even when they're not full, and very significant effect on their appetite, and so they don't eat as much and lose weight, so it's quite variable, actually. Cachectic, meaning they lost so much weight that they're very skinny and are kind of not getting enough nutrition.

Dan Keller 9:56 What other behavioral or dietary changes are there? Certain foods that are worse than others, or is it just generalized—you can't tolerate anything when you're feeling nauseous?

Dr. Andrew Feigin 10:07 I mean, occasionally you'll see patients who will say certain foods seem to make it worse than others, but I would say I couldn't give any kind of generalizations about that. You know, when we start telling people to take their carbidopa/levodopa with food, it gets into the issue that a lot of people are familiar with these days, that protein can interfere with the absorption of levodopa, and so I would say that I try to minimize that as a concern. Most people who are just starting on levodopa are not really noticing either too much on-off types of fluctuations, meaning their levodopa is kicking in or it's wearing off, and so this kind of difference between whether they take it with protein-containing food or not is not a big difference, and so I try to minimize that, but for some people that could be an issue.

Dan Keller 10:52 If protein interferes with the absorption of levodopa, does it also ameliorate some of the effects in the gut, or is it just bad news, you're not absorbing it, but the levodopa is still causing nausea?

Dr. Andrew Feigin 11:05 It would limit the amount of levodopa you're absorbing, and so it would reduce the amount of levodopa being peripherally converted to dopamine, so it could alleviate the nausea by that mechanism. But the concern would be that it would also limit the effectiveness of the levodopa, although, as I said, in my experience, I think when people are first starting on levodopa, this issue of not noticing a complete effect of the medication because of eating it with protein, I wouldn't say it never happens, but it's not the most common problem.

Dan Keller 11:33 What about dividing small meals across the day? Would that help?

Dr. Andrew Feigin 11:38 That can be helpful when people have gastroparesis, limited or slow emptying of the stomach. Yeah, we often recommend smaller but more frequent meals, more fluids, just to kind of give the stomach a chance to get empty, so that sensation of fullness that can lead to nausea doesn't build up.

Dan Keller 11:55 What about increasing carbohydrates, or increasing glucose, and water, and electrolytes?

Dr. Andrew Feigin 12:01 We always are recommending people keep themselves well hydrated, in particular with electrolytes, not just pure water. We're getting away a little bit from nausea here, but one of the other potential side effects of levodopa being converted to dopamine before it gets into the brain is that people can have drops in their blood pressure, causing lightheadedness, and there are other potential side effects, constipation, and other issues. So we do recommend that people keep themselves well hydrated, especially with fluids containing electrolytes.

Dan Keller 12:32 And of course exercise is recommended for everything. Is it recommended here?

Dr. Andrew Feigin 12:37 There are reports that people who do more exercise can improve the motility of the GI system, and so it potentially alleviates some of the nausea that they get from the Parkinson's disease, and potentially even from side effects of levodopa. There's no downside to exercise. We recommend exercise for all of our Parkinson's patients, regardless, but I think it can be helpful for nausea as well.

Dan Keller 12:59 I guess if you had to encapsulate the overall recommendation, what would you tell people who either want to avoid nausea or have to deal with it?

Dr. Andrew Feigin 13:08 So, I would say, first of all, I think figuring out the cause of the nausea is important. Is it from the Parkinson's disease, or is it a side effect of medication? If it's from the Parkinson's disease, from the poor gastric emptying, for example, poor GI motility, things like what we talked about, eating smaller meals, keeping yourself well hydrated, are important non-medical ways of dealing with it.

I think if you're just getting started on levodopa, and it's obvious—in many cases, it is just obvious—that's what's causing people to get nauseous. They take their medication, they get nauseous, some period of time later, the nausea goes away. In that situation, the first thing we usually advise people to do is to try to take the carbidopa/levodopa with food and with a reasonable amount of water. If that doesn't work, then you should talk to your doctor about it, and there are other things that can be done, such as extra carbidopa with the medication, and of course we always recommend exercise as well.

Dan Keller 14:02 You don't want to just keep adding drugs upon drugs and things like that, but are there drugs that promote gastric emptying?

Dr. Andrew Feigin 14:09 As I mentioned, this drug Domperidone, which blocks dopamine, but only peripherally, essentially works that way.

Dan Keller 14:15 But it's not available here, so people have to order it from Canada, right? And there are—

Dr. Andrew Feigin 14:19 There are other drugs that also block dopamine that promote GI motility and gastric emptying, like a brand name drug called Reglan or Metoclopramide, but that drug is really contraindicated in people with Parkinson's disease, because it crosses the blood-brain barrier and blocks dopamine in the brain. So that's not really a viable treatment.

Dan Keller 14:36 Is there anything important or interesting we've missed?

Dr. Andrew Feigin 14:40 My feeling about nausea in Parkinson's disease is that most people can find a way to tolerate their medication. Most people can find a way to ameliorate some of the nausea that can come with Parkinson's disease. For those who struggle with it, it can be very frustrating, and it can lead to the need to take drugs like Domperidone, although we try to avoid it as much as possible.

Dan Keller 15:04 Very good, good advice. Thank you.

Dr. Andrew Feigin 15:06 My pleasure.

Dan Keller 15:16 For more information on nausea in Parkinson's, go to our newly designed website at parkinson.org, click on the three stacked bars at the top right side of the page, and enter nausea in the search box. On page four of the search results, you'll see a link to a page on constipation and nausea. You can find more information on gastroparesis by visiting parkinson.org/expertbriefings. If you scroll down that page, you'll see a list of past webinars. Look for number 24 called Non-Motor Symptoms: What's New? The relevant section begins at about 37 minutes and 20 seconds on the timeline. There is also a blog post on medications in development to promote gastric motility and emptying, which you can find by searching on promotility.

As always, our helpline information specialists are available to answer questions in English or Spanish about today's topic, or anything else having to do with Parkinson's, including finding your way around our newly redesigned website. News and updates about future events and resources are available by joining our email list at the bottom of our website's home page. If you want to leave feedback on this podcast, or any other subject, you can do it at parkinson.org/feedback. If you enjoyed this podcast, be sure to subscribe and rate and review the series on Apple Podcasts, or wherever you get your podcasts.

At the Parkinson's Foundation, our mission is to help every person diagnosed with Parkinson's live the best possible life today. To that end, we'll be bringing you a new episode in this podcast series every other week. Till next time, for more information and resources, visit parkinson.org or call our toll-free helpline at 1-800-4PD-INFO. That's 1-800-473-4636. Thank you for listening.

Dr. Andrew Feigin is a Movement Disorders neurologist and Professor of Neurology at NYU Langone Health where he is the Director the Marlene and Paolo Fresco Institute for Parkinson’s and Movement Disorders. He has been involved in clinical research for Parkinson’s disease and related disorders for more than 25 years, and he has been a site principal investigator on more than 30 National Institute of Health and industry-sponsored clinical trials of new treatments for Parkinson’s disease (PD) and Huntington’s disease (HD). In addition, Dr. Feigin has had leadership roles as PI or co-PI in several early phase clinical trials and advanced multicenter clinical trials, including gene therapy trials for PD. Dr. Feigin’s independent research has focused on the use of state-of-the-art imaging methods to elucidate the mechanisms underlying current therapies for PD and HD. In addition to his research interests, Dr. Feigin has remained a committed and busy clinician caring for patients with PD, and related movement disorders.