The Johns Hopkins Associate Professor spoke about the current therapeutic landscape of restless leg syndrome, an often misdiagnosed disorder.
Rachel Salas, MD, Associate Professor of Neurology, Johns Hopkins Medicine
Rachel Salas, MD
Restless leg syndrome (RSL), a disorder that has become much more recognizable in recent years, is still often misdiagnosed. While there are treatments available for patients with RSL, many of times they come with side effects that lead to an increase in augmentation.
Aside from dopamine agonists, opioids are another viable option for treatment of RSL, however, in the current opioid crisis, it’s quite difficult for physicians to prescribe them. Rachel Salas, MD, Associate Professor, Neurology and Nursing at Johns Hopkins Medicine, spoke with NeurologyLive in an interview to provide further insight into the current therapeutic landscape, hopeful that additional treatment strategies will soon be available for patients.
Rachel Salas, MD: For restless leg syndrome (RLS), there are medications out there that are FDA approved and work, but they come with side-effects and can actually cause worsening of symptoms. For example, the dopamine agonist can cause augmentation and people can have these impulse compulsive behaviors, so these are things at our center that we’re constantly seeing in patients.
A good example for restless leg treatment, beyond the dopamine agonists, are opioids which, right now, in the current opioid crisis, is very difficult for us, because we know opioids at a very low dose work really well for RLS. The problem is, with the opioid crisis, and because our peers and medicine aren’t familiar with our practice parameters for RLS, you don’t see the connection there, but in reality, RLS is a different type of beast from chronic pain. We don’t see dependence, we don’t use high doses, so that is a pretty good treatment strategy for RLS, however, sleep centers are not set up as a pain center and it’s been more difficult to initiate and maintain these patients on even low dose opioids.
One of the issues I see is that even though it’s in our practice parameters, for people who have been augmented or other medications have not worked, opioids while they’re a viable option, it’s very difficult for us to start patients. In fact, we’re really not able to do it, so we’ve combined with our colleagues in pain clinics that are comfortable, familiar and educated on those with RLS, and we have a partnership with some of the pain specialists. I see this as really a step back for RLS patients because opioids are a serious problem it’s negatively impacting our patient population.
With the dopamine antagonist, there’s the risk of augmentation, so this is where the dopamine agonist works, it helps their symptoms, but then over time the RLS gets worse, so you increase their medication, but it doesn’t get better. It’s this pattern and that’s what augmentation is, that the symptoms are actually worsening not because of the disease itself, but because of the medication.
When treating with dopamine agonists it’s important to be aware that augmentation can happen and does happen, and these patients can also develop compulsive impulse behaviors, usually not to the degree of people with Parkinson, because these are on higher doses of dopamine and so they can get into these compulsive impulse behaviors like gambling. RLS patients can develop this too, but usually to a less degree where it might be under the radar with family members.
With RLS there’s certainly behavioral modifications, I try to send several of my patients with severe RLS to the sleep behavior psychologist as well, to try and improve bedtime practices. All of these things can positively affect sleep and we try to make that part of the management, some patients may also try meditation, acupuncture, massage, things like that can be helpful.
We also use antiepileptic medications quite frequently for chronic RLS and those can work well, but again, they have side effects too, so we have to work with them. Often in our clinic, people have tried medications in the past, but both patients and providers need to be open to trying therapies that were tried previously and maybe didn’t necessarily work. Many times, it’s not just about taking the medication, but it actually has a lot to do with the timing of medication. I find that many times patients were taking the medication at suboptimal times, so I’ll try medications that they think didn’t work, but we just time it more appropriately based on the symptoms and I can have more success doing that.
In talking to my colleagues who have patients with RLS, I think before switching medications, if it’s because the medication isn’t working, we need to look at the timing, because you want to make sure that the medication is on board before the RLS starts, because once RLS starts, taking medications may not be as helpful.
It’s important to look for exacerbators, people take medicine over the counter all the time, especially cold season, so antihistamines are huge exacerbators for RLS and not many people aren’t aware of that, not only patients but health care providers. There’re dopamine medications that we’ll see for nausea or some of the antipsychotics that have dopamine blockers and those medications if given to an RLS patient can be very bad, they can exacerbate their RLS.
I trained under Richard Allen, PhD, and Chris Earley, MD, PhD, who have done a lot of work in iron and RLS, and so we often check iron status and we have patients that will even receive iron infusions a couple times a year and that’s all they need. I think looking at all of these other potential causes or exacerbators is really key and it’s something that I really try to let my peers in other fields who are taking care of RSL patients be aware of.
We just completed a large study using transcranial magnetic stimulation to better understand the neurobiology in patients with moderate to severe RLS. We weren’t looking at therapy in this study, but the study does show that those with RLS actually have differences in cortical excitability. When looking toward the future, hopefully, there’ll be opportunities to perhaps target have this excitability as a potential treatment strategy with stimulation. There’s a lot of interest, not just in sleep, but in other medical disorders even with medical marijuana and things like that, so I think we’re going to see at least more studies come out, I certainly know patients are trying that on their own, but I think it needs more research behind it, because at the moment there’s no quantity or frequency. I think while patients are very interested or sometimes desperate to try these therapies, we really don’t know the long-term consequences, what type or how often to use it. I think there’s going to be more research in those areas and potentially, there may be some opportunities there, but maybe not, we still have to see. That’s where we are with RLS.
RS: RLS is something that I think a lot of health care providers are maybe not too familiar with or maybe don’t see. One of my big messages is to remember that RLS is a clinical diagnosis, so sometimes health care providers may order a sleep study and in the sleep study we report this patient has periodic limb movements during sleep and just based on that, may be diagnosed with RLS and that is not correct, and that’s actually common.
One of my points to my peers would be to remember that RLS is a clinical diagnosis, patients have to meet all of the criteria for RLS, and if they have leg movements on a sleep study and poor sleep, then you should evaluate, ask them questions to see if they meet the criteria for RLS, or refer them to a sleep specialist or a movement neurologist for further evaluation. I can’t tell you how often I see patients with just leg kicks with no RLS symptoms that were initiated on dopamine agonists, and again these medications come with side effects and may even trigger RLS.
The other thing is that if you’re concerned a patient has RLS and it’s happening more than 3 times a week, then you’re moving toward someone that could probably benefit from potentially treatment—before initiating anything it may be worth referring that patient, so we can look for treatable causes. For example, iron deficiency, it’s not just about checking a quick iron panel, we have specific things and levels that we’re looking for, so even though they might be normal, they may be low normal, but we still could treat them. If you feel like this patient probably has RLS, it may be worth referring at least 1 time to confirm the diagnosis and then to do a thorough evaluation, so that way there may be things the patient has taken over the counter, or there may other things that can be addressed before actually starting medication.
In terms of opioids, sometimes we’re recommending them and sometimes people live in small cities where there’s not a sleep specialist or a pain center and a lot of times the primary care physician since they have a long-term relationship with the patients, can initiate low-dose opioids. Sometimes patients will come and see us at Hopkins to diagnose or confirm the diagnosis and we see that the patient has tried every therapy, low-dose opioids are a great option for this patient. In those cases, the primary care physician should really try to work or connect with the sleep center and experts in RLS to have guidance. Now with telemedicine picking up more momentum, we’re going to be able to really better maintain these relationships with a lot of primary care physicians under our guidance for next steps, and I think this is going to provide better care.
One of the things I wanted to say with opioids is with RSL, you have to remember to reassess for things like apnea, because low-dose opioids and sleeping pills like Ambien or Lunesta, which we often see given to patients with sleep problems, weren’t adequately assessed for apnea. Any sedative is going to worsen apnea and I think people need to be aware of that, plus, we know from studies that our RLS patients if they have untreated apnea, that’s negatively going to impact their RLS. You have to remember to identify if the patient is at risk for apnea; maybe they’re not right now, but in 5 years that could be a different scenario, peoples risk factors do change.
This is definitely a new point that I’m trying to get out to my colleagues. If you want to try a sleeping pill or something sedative wise for patients that may be appropriate to try, especially if there have a trigger like a death in the family and it’s acute insomnia, you might want to at least screen for apnea, because a patient may get into trouble at night.
Transcript edited for clarity.