Evo Terra (Host): This is Expert Insights with the Carle Foundation Hospital. I'm Evo Terra, and today I'm joined by Dr. Rachel Immen, a Board-Certified Sleep Medicine Doctor for a conversation about recent changes to the clinical guidelines for restless leg syndrome management. Thanks for being here, Dr. Immen.

Rachel Immen, MD: Thank you for having me. I'm excited to talk about sleep medicine.

Host: Oh yeah, I'm, I'm excited to hear about this stuff. I know that there has been some changes in recommendations for how we treat specifically restless leg syndrome. Can you talk about those changes?

Rachel Immen, MD: Absolutely. There are some really significant changes that have completely changed the landscape of restless leg syndrome treatment. A lot of different things have changed dramatically.

Host: So let's get into some of those changes and why those changes have happened. Uh, maybe we start with the initial steps of restless leg syndrome management. What's changed there?

Rachel Immen, MD: So, now the foundation of treating restless legs and those initial steps is paying attention to extremely important two steps, which is one, is there anything making restless leg show up right now or be worse right now that we could remove as an offending trigger? Like can we clean things up and prove contributing factors? And how does iron play into the current picture? So the first two steps are not medication.

Host: Great. Restless leg syndrome. Maybe we should just do a quick overview of what that is.

Rachel Immen, MD: Uh, that's a great, great point. So, restless leg syndrome, you know it if you have it. It's a very uncomfortable urge to move the legs, and it typically is worse with rest. Better with movement and it has a circadian pattern. So, it gets worse in the evening. It's really important with restless legs, that urge to move story with a circadian pattern is the core of the diagnosis of restless legs.

Host: Okay. So iron plays a role. Tell me about that.

Rachel Immen, MD: Iron is a key component in the brain when we need to make dopamine and if iron is lacking, the brain's dopamine systems get off kilter and restless legs presents or gets much worse. And so by restoring iron, we can significantly improve the experience that patients have with their restless legs.

It can get significantly better by resolving one of the reasons why it showed up or got worse in the first place.

Host: That makes sense. I love learning about how the brain and neurochemistry and all these kind of things work. Speaking of that, I have heard of these things called gabapentinoids and as a treatment possibly for RLS, but those are very large words, so perhaps you can explain that to me.

Rachel Immen, MD: So, after removing any triggers like offending medications or untreated sleep disorders and making sure that iron stores are where they need to be; if restless leg symptoms are still present, then we look at medication and these gabapentinoids are now first-line treatment and gabapentinoids, are three different medications, Gabapentin, pregabalin also called Lyrica and Gabapentin anacarbill, and they quiet down the nerves in the legs so that the signaling and the uncomfortable urge is less noisy, less apparent, less problematic.

Host: Got it. Quieter nerves obviously means less of the motion that is taking place. Understood. You said removing triggers earlier, what are these common triggers? I mean, I don't have to change my bedding, do I?

Rachel Immen, MD: So people try, because if you have restless legs, you're willing to try just about anything to make it go away. But the ones that we know really make a difference are untreated sleep apnea, can make restless legs much worse. Three main groups of medications, including antihistamines, serotonin medicines, and some dopamine medications.

Those are really, large classes of medications, and all three of those can make restless legs worse. And then alcohol, caffeine, and sleep deprivation also make restless legs worse. And if we remove those triggers, restless legs can improve substantially without even adding a first step medication.

Host: Okay. That's interesting. Now, as a person who takes one or all of those things, does that mean I'm at a predisposed risk of getting restless leg syndrome if I don't have one?

Rachel Immen, MD: So, it is a contributing factor, but a lot goes into developing restless legs. There's a strong genetic component and it's also linked to other health conditions. So being on one of those medications alone is not enough of a risk factor. But if anyone does develop restless legs and they are on one of those, they should pay close attention to the role it plays.

Host: Okay. You brought up the word dopamine. Always a fun word to talk about. Also I know that we have these agonists that are out there, which is also a brand new term for me, thanks to the GLP-1 agonists that are out there. And I know there's a big shift that's happened in guidance regarding using these dopamine agonists. Can you talk about that?

Rachel Immen, MD: Absolutely. So, this is such a difficult aspect of treatment because, back in 2012, the guidelines told us dopamine agonists were the solution. And now in 2025, the guidelines tell us the dopamine agonists are the problem. So dopamine agonists help increase the dopamine pathway activity in the brain, which initially does significantly improve restless legs, however, over time, these dopamine agonists actually cause the entire system to get adapted to new baselines that are not healthy. And over time, they actually make the restless legs much worse. It starts earlier in the day. Symptoms are more frequent and intense and restless leg syndrome symptoms can actually move beyond the legs into the torso, the shoulders and the arms.

So the dopamine agonist started off as a solution, but over time they've become the problem.

Host: So I would imagine, and you please tell me if this is not the case, that there might be patients out there who've been working with their RLS for some time who are still taking dopamine agonists. Yeah?

Rachel Immen, MD: Yes, because it was the first-line treatment now for over a decade, prior to this recent publication, it was our go-to medication. And restless legs is such a difficult condition to have. And when a patient takes a dopamine agonist for the first-time and it magically resolves their symptoms, it feels like a miracle pill.

And so very well received and clinicians are happy when their patients are happy. But my concern and everyone's concern has been, over time when you need a higher dose and then an earlier in the day dose, all of those things are really significant red flags. So while a lot of people are on them, and they were at one point a good treatment, it's not a good plan going forward.

And I do want to add a huge point of caution here. Do not abruptly stop a dopamine agonist. So if a patient is on a dopamine agonist like pramipexole, ropinirole, rotigotine, if they were to abruptly stop it, they would likely have way worse rebound symptoms, terrible side effects, and it can really be miserable and even unsafe.

So these medications have to be handled carefully and especially in the situation of augmentation. It's complex and needs a lot of care.

Host: So if, you are curious about that as a listener to this show, don't stop. Go call your doctor like right now and make make a call. Get an appointment. Okay. So let's talk about refractory RLS, which I means it, what, it just comes back again. I'm guessing Right? And some treatment options for this.

Rachel Immen, MD: Yeah, so there definitely are refractory or treatment resistant cases, where the RLS is really severe and it's not responding to removing triggers or increasing iron levels, or even maybe with gabapentinoid medication or dopamine agonist, nothing is working and the person is miserable. So in those severe refractory cases, the guidelines say that, there may be a role for opioid medication.

For a small group of patients, opioids can be life-changing. They're absolutely not the starting point for RLS treatment, but they can be a very powerful treatment when used carefully and appropriately.

Host: Yeah. Appropriate use of opioids. Definitely with the epidemic that we're seeing right now for a variety of those things. But we need to not forget these are medications first, and we should be using them correctly. So what about non- pharmacological, or device-based therapies I've been hearing about?

Rachel Immen, MD: Device based therapies. I think if, anyone was to search online for device-based therapy for restless leg syndrome, they would probably come up with many options. I'm sure it's a very large industry. Again, if you have restless legs, it's so miserable. People are willing to try just about anything to improve it.

And now the guidelines actually do include a device that has research behind it and is indicated for treatment, and it's a high frequency peroneal nerve stimulator. It's rather new, and so it'll be really interesting to see over time where this goes. But I love the idea that we're including treatments that are not medications, that are not pills.

Host: Absolutely. And where is this peroneal nerve and how does it get stimulated?

Rachel Immen, MD: Okay. So it's in the leg and it's similar to a tens unit where it's sending electrical shocks and it is dialed in in terms of what the frequency is and the stimulus delivered to the nerve.

Host: And I appreciate you bringing up the evidence based, right? We have, like you said, in medical terms, the Dr. Google is not always your friend or rarely ever is your friend, from what I understand. Right. There are a lot of things marketed to fix, but what does the evidence say?

And that's what you've brought us today, these evidence-based treatment options for RLS, anything else you would care to add to this.

Rachel Immen, MD: I think overall, my strongest thing is that people should know iron is foundational. If you don't take away anything else, know that iron is foundational. And then on top of that would be medications really have to be considered carefully and across a lot of different groups of medicine. Medication is actually not always the solution, but oftentimes the problem.

Host: Great words of advice. Dr. Immen, thank you very much for all of the information today.

Rachel Immen, MD: Yes. Thank you for having me. It was great to talk with you Evo.

Host: And that wraps up this episode of Expert Insights with the Carle Foundation Hospital. I'm Evo Terra. For more information and to get connected with one of our providers, please visit carle.org. That's C-A-R-L-E.org. Or for a listing of Carle providers and to view Carle-sponsored educational activities, head on over to our website@carleconnect.com.