Episode 138: Medication-Induced Parkinsonism - How is it Different?

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.

Parkinson's disease is a neurological condition characterized by motor symptoms of stiffness, slow movements, resting tremors, and postural instability. It's caused by a lack of dopamine production in the brain. Non-motor symptoms of depression, loss of the sense of smell, gastric problems, and mood and cognitive changes are also common, but another group of disorders with a variety of causes may mimic Parkinson's disease. These syndromes have some features like Parkinson's and are referred to as parkinsonisms, also called atypical Parkinson's disease or Parkinson's Plus.

I spoke with Dr. Cheryl Waters of Columbia University in New York City about one cause of parkinsonism: the use of medications to treat other conditions. In particular, medications used in psychiatry to treat psychoses may precipitate medication-induced parkinsonism. I first asked her to tell me the difference between Parkinson's disease and parkinsonism.

Dr. Cheryl Waters 1:53 So, Parkinson's disease is something that we diagnose when we have a number of features, and parkinsonism is when we think there might be some other explanation than we see with regular Parkinson's disease.

Dan Keller 2:08 Is one of the major other explanations drugs?

Dr. Cheryl Waters 2:13 So drugs can produce a parkinsonism, and that's a very good question. It's not that common, interestingly, but it's very, very important to recognize that, because it's reversible.

Dan Keller 2:25 What else may cause it?

Dr. Cheryl Waters 2:28 What else may cause parkinsonism? Parkinsonism is a term we use when we're trying to explain that it's not quite fitting the bill, that it might be a little bit atypical, so that's not necessarily the topic we're discussing today, but there are other diseases that can look like Parkinson's and not be Parkinson's disease.

Dan Keller 2:48 How can you distinguish parkinsonism from Parkinson's disease?

Dr. Cheryl Waters 2:53 So, parkinsonism can be from a lot of other different diseases, like strokes or other degenerative diseases, such as progressive supranuclear palsy, multiple system atrophy. There are other reasons for parkinsonism. The secondary causes, which is what we're talking about today, like what other things cause it—medications can cause parkinsonism.

Dan Keller 3:15 And in terms of how the patient appears or presents, can you distinguish parkinsonism from Parkinson's disease?

Dr. Cheryl Waters 3:24 We're only talking today about drug-induced, medication-induced parkinsonism, and what's so intriguing is sometimes you can't tell them apart, and that's something I learned many, many, many years ago. Now, the question is, is it hard to tell them apart because the patient has a little bit of underlying Parkinson's, and then you add the medicine to make it worse, or is it that you just can't tell them apart because sometimes this disease can even present the same way as Parkinson's, with what we call asymmetry, one side more than the other.

The things that I think help me distinguish when I see a patient with drug-induced parkinsonism versus Parkinson's, I look for things like the pre-motor features. For example, does the patient have a loss of sense of smell? You wouldn't expect that from a medication. You wouldn't expect that from a drug-induced parkinsonism, but loss of sense of smell is commonly seen in Parkinson's disease. Also, patients with Parkinson's can act out their dreams. That is something called REM behavior disorder. You wouldn't expect that with medication-induced parkinsonism. But to say, because somebody has it just on one side, not both sides, that it has to be Parkinson's disease versus drug-induced is not necessarily correct. It can be asymmetric even with drug-induced parkinsonism.

Dan Keller 4:45 Is that the traditional thinking? I thought they would always say drug-induced parkinsonism is symmetrical as opposed to Parkinson's.

Dr. Cheryl Waters 4:56 Very good point, and I think that I remember as a very young faculty member presenting a case at a conference, and being cut down, saying, "No, it has to do with how many brain cells they have. There could be asymmetry, so don't be so certain." If the patient is exposed to these medications, it could be drug-induced parkinsonism.

Dan Keller 5:13 May drug-induced parkinsonism reveal a risk or beginnings of Parkinson's disease?

Dr. Cheryl Waters 5:20 So that's a great question. Absolutely, it could be that the patient was incipient—they were about to develop Parkinson's disease, they were exposed to one of these medications, and then became more Parkinsonian. So, yes, they could have some underlying Parkinson's.

Dan Keller 5:39 In drug-induced parkinsonism, would people typically also have or not have autonomic symptoms like constipation and sweating and blood pressure irregularities?

Dr. Cheryl Waters 5:51 So that's also a great question about the autonomic features of Parkinson's. You wouldn't expect them with a drug-induced parkinsonism. However, when you have drug-induced parkinsonism, it's usually from one of the drugs that are given by psychiatrists, right? They're usually from the antipsychotic medications. That being said, they could be on other medications from psychiatry, some of which could cause the drops in blood pressure, the constipation, the blurred vision. So you can see, you really have to know your medications. You have to be a pharmacologist to sort this out.

Dan Keller 6:24 How do you get a good read on all the medications they're taking? People seem to ignore certain things.

Dr. Cheryl Waters 6:31 Well, it comes up in our electronic medical record, so I know what medications the patients are taking, because it usually pops up. Sometimes too many pop up because they're no longer on them, but I review the medication list with the patient. I'm very aware of the medicines that cause side effects, and I go over them with the patients. There are a lot of different side effects, not just the parkinsonism.

Dan Keller 6:52 What are some of the medications that are traditional or usual that you would see causing drug-induced parkinsonism?

Dr. Cheryl Waters 6:58 So that's an excellent question. So, the most common medications that can cause drug-induced parkinsonism are the ones that are called antipsychotics, even the ones that are currently being advertised on television as the newer medications. They may cause drug-induced parkinsonism. The older ones certainly do, and the only other drug that doesn't fit into that category that can cause it is a drug we use for heartburn or stomach problems called metoclopramide, and that has commonly been used in patients who are diabetic or for people who have heartburn, and that can also, by the same mechanism, produce drug-induced parkinsonism.

Dan Keller 7:38 Does metoclopramide interfere in a person with Parkinson's disease with levodopa?

Dr. Cheryl Waters 7:45 It blocks the dopamine receptor. So, if you've got Parkinson's disease, you should not be on metoclopramide. It should be in your chart that you're allergic to metoclopramide, and your doctor should be aware of that. So, nobody with Parkinson's disease should receive metoclopramide. Patients who receive metoclopramide for other things, like lots of people are using it for migraine—those are often young patients, they don't get Parkinson's, and they'll take it for the occasional migraine. But people that are given it for long periods of time for their heartburn or reflux or intestinal issues might develop some stiffness or slowness, and they don't realize that it's from the drug.

Dan Keller 8:20 So if it interferes with dopamine receptors in a Parkinson's patient, which is now being supplied by external levodopa, does it also compete with natural endogenous dopamine at those receptors?

Dr. Cheryl Waters 8:37 Right. So, if we think about this—and I had a perfect example of a patient that came to my clinic 10 or 15 years ago, and he suddenly was worse, his Parkinson's was suddenly worse, and it took some prying. My nurse practitioner and I pried. We realized—this was before we had electronic medical records—we figured out that he had been placed on metoclopramide for his heartburn, and that was the explanation for why his Parkinson's got worse. So whether you have any remaining intrinsic dopamine or whether you're taking your levodopa externally, metoclopramide and most of the antipsychotics will block dopamine receptors.

Now we know sometimes people need antipsychotic medications, and so maybe you might consider which ones can you take safely. If you have Parkinson's, we have found that you could take quetiapine safely. The psychiatrists worry when you get up to very, very high doses of this medication, but we don't tend to see patients on very, very high doses. They can also take clozapine, which is an old-fashioned antipsychotic—not a lot of people use it anymore. And then you could also take pimavanserin, or Nuplazid; that's a newer antipsychotic that does not seem to produce parkinsonism.

Dan Keller 9:49 If someone has drug-induced parkinsonism, is it reversible by changing medication or withholding medication?

Dr. Cheryl Waters 9:56 So that's such an excellent question. So the challenge I have as a clinician is I will see patients where you have no option—they have to stay on the antipsychotic medication, and you could ask the psychiatrist if there's any room to reduce the dose, but sometimes we don't have any recourse but to just follow the patient and accept a little bit of parkinsonism they might have as a side effect to control their psychotic features.

Dan Keller 10:25 Is there ever a situation where you change drugs or take them off of a drug and they still have residual drug-induced parkinsonism?

Dr. Cheryl Waters 10:33 So that's a very good question too, because I think that people don't realize how long you have to wait to eliminate drug-induced parkinsonism. Some of my colleagues will say, "Well, it's been two to three months. How come it hasn't gone away?" It can take up to a year, even a year and a half, before you see the complete resolution from these medications. Now, once again, there could be a little bit of underlying Parkinson's too, so you don't know for sure, but you could always measure that by looking at a special type of scan called a DaTscan. If you want to, it's not always necessary to test for that.

Dan Keller 11:06 It seems months or a full year to clear a drug from your system is a long time. Does the drug itself change the receptor or the number of receptors of an environment, so that you're not even responding to your own dopamine for a long, long time afterwards?

Dr. Cheryl Waters 11:23 Well, I think that they certainly affect the receptors, because in addition to the drug-induced parkinsonism, these drugs can produce another condition called tardive dyskinesia. So, they can affect your receptors for certain. I don't think it's the same with clearing metoclopramide, but clearing the antipsychotics, you have to be patient.

Dan Keller 11:41 So, what's the message to people who are experiencing symptoms, whether it's drug-induced parkinsonism or Parkinson's, because they don't know—so what should they do?

Dr. Cheryl Waters 11:54 Well, I think that, first of all, every single time you go to the doctor, review the medications, and hope your doctors understand what medications you're taking. But these medications are usually prescribed by psychiatrists. So, the psychiatrists need to be made aware. If you're the neurologist examining the patient, you need to let the psychiatrist know you're seeing some findings of parkinsonism, because the psychiatrist needs to be made aware that perhaps they could lower the dose, or is there some other route we can take to manage this patient.

Dan Keller 12:23 Is there anything we've missed or important to add on the subject of drug-induced parkinsonism?

Dr. Cheryl Waters 12:28 It's exceedingly rare. It's not that common, but it is something, as a movement disorder practitioner, I've seen often. But for patients with idiopathic Parkinson's disease, they're unlikely to be placed on these medications routinely.

Dan Keller 12:42 I suppose also, it's worth checking out because you may find a diagnosis of Parkinson's disease early and tell people to start exercising, or whatever is going to help Parkinson's disease before it gets worse.

Dr. Cheryl Waters 12:56 That's true. I've always been of the philosophy that the psychiatric disorder takes actually the most paramount position, so I think that to keep the patient's mood level and good, it might be that we pay a little price with some parkinsonism. So, if they need those medications to function in daily life, then I will accept a little bit, but I still examine the patients at intervals to see how they're doing.

Dan Keller 13:23 Pretty good. I appreciate it. Thank you.

Dr. Cheryl Waters 13:25 You're welcome. It's been a pleasure.

Dan Keller 13:35 To find out more about parkinsonism versus Parkinson's disease, you can search parkinson at parkinson.org/pdlibrary and filter by fact sheet. This page discusses differences between the two, as well as several of the underlying causes of parkinsonism, including medication-induced parkinsonism. For more on the subject, you can listen to one of our past podcasts, titled Parkinson's Disease vs. Parkinsonism: What's the Difference?

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 homepage. 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.

Cheryl Waters MD FRCP(C), holds bachelors and masters degrees in Pharmacology from the University of Toronto, where she studied dopamine receptor function with Philip Seeman. She completed medical school at University of Toronto, an internship at University of Chicago, and returned to Toronto for Internal Medicine, Neurology and a fellowship in Clinical Pharmacology. She moved to California and developed the Movement Disorder Program at the University of Southern California. Dr. Waters then moved to New York to take on her current position as Chief of Clinical Practice and Services in the Division of Movement Disorders. She has been involved in research on the genetics of Parkinson's disease and the treatment of this disorder. She has authored numerous articles and book chapters and a book in its seventh edition: Diagnosis and Management of Parkinson's Disease. She has been an investigator in numerous studies involving a variety of new medical and surgical treatments. She is the first to hold the Albert B. and Judith L. Glickman Chair in Neurology.