Walk Through Updated Guidelines for Restless Legs Syndrome

In this episode, Rachel Cole, PharmD, walks us through the evolving landscape of restless leg syndrome management, highlighting why dopamine agonists are no longer first-line therapy and what that means for clinical practice. 

You’ll learn about the importance of checking for iron deficiency, practical non-drug interventions, and alternative medications like gabapentin and pregabalin. 

Rachel shares actionable tips for educating patients, managing tricky cases, and staying up to date with the latest sleep medicine guidelines, so you can take confident steps forward in caring for patients with RLS.

This is an excerpt from our July 2025 Pharmacy Essential Updates continuing education webinar series.

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CE Information:

TRC Healthcare offers CE credit for this podcast for pharmacist subscribers at our platinum level or higher and pharmacy technician subscribers. Log in to your Pharmacist’s Letter or Pharmacy Technician’s Letter account and look for the title of this podcast in the list of available CE courses. None of the speakers have anything to disclose.

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Clinical Resources from Pharmacist’s Letter, Pharmacy Technician’s Letter, and Prescriber Insights: 

• Article: Stay in Step With Treatments for Restless Legs Syndrome
• Chart: Oral Iron Comparison and Practical Considerations for Use

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Transcript

This transcript is automatically generated. 

00:00:04 Narrator

Welcome to Clinical Capsules from TRC Healthcare, your go-to podcast for fast, evidence-based insights. 

00:00:12 Narrator

On this episode, Clinical Pharmacist Rachel Cole examines the latest updates in restless leg syndrome management, including what new treatment strategies you should know about, in an excerpt from our popular Pharmacy Essential Updates webinar series.  

00:00:25 Narrator

TRC has been a trusted resource for healthcare professionals for over 40 years—and now we’re bringing that expertise straight to your ears every 2nd and 4th Tuesday, in bite-sized, actionable episodes…right here on Clinical Capsules.

00:00:42 Narrator

This podcast offers Continuing Education credit for pharmacists and pharmacy technicians. Please log in to your Pharmacist’s Letter or Pharmacy Technician’s Letter account and look for the title of this podcast in the list of available CE courses.

00:00:55 Narrator

None of the speakers have anything to disclose. 

00:00:58 Narrator

Let’s get moving and dig into the episode…

00:01:08 Rachel Cole

We're going to be looking at the management of restless leg syndrome. I'm excited to look at this with you. So, there have been some updates to the treatment guidelines for restless leg syndrome and restless leg syndrome is a common problem.

00:01:23 Rachel Cole

And our article says dopamine agonists are no longer first line for restless leg syndrome. According to the American Academy of Sleep Medicine. And there are actually some recent guidelines that came out about this that conditionally recommend against these agents. So, let's dive into this.

00:01:41 Rachel Cole

So, if we think about the symptoms of RLS overall, it's that classic symptom, the strong urge to move the legs or the arms, usually due to an uncomfortable or unpleasant feeling. And those urges occur, especially when the patient is at rest or when they're less active. So especially in the evening.

00:02:01 Rachel Cole

Overnight or early morning and moving the limbs temporarily helps to relieve those sensations.

00:02:09 Rachel Cole

And often the exact cause of RLS is not known. One theory is its due to abnormal dopamine transmission, but in many cases RLS is linked to iron deficiency or pregnancy, end stage renal disease or certain medications like SSRI's, SNRI's, statins and antihistamines.

00:02:31 Rachel Cole

So, when it comes to managing RLS, non-drug measures may be helpful for some patients.

00:02:37 Rachel Cole

So, leg massage or stretches may give some acute relief. Walking around can also help, we said. Those symptoms are usually relieved by movement.

00:02:47 Rachel Cole

And then moderate intensity regular exercise may also give some possible long-term improvement, but extremely strenuous exercise like long distance running or even exercise within a couple hours of going to bed, may actually worsen symptoms for some patients.

00:03:04 Rachel Cole

Now, if the patient has to be still for long periods of time, distractions such as puzzles or reading may be helpful, and exposing the legs to temperature changes such as heating pads or cold compresses can also help some patients, and then limiting tobacco, alcohol and caffeine can also help.

00:03:27 Rachel Cole

And since brain iron deficiency has gained recognition as a likely cause of RLS, supplementation is now considered first line treatment. It's recommended to check serum iron, including ferritin and transferrin saturation in all patients with RLS, and supplement if needed.

00:03:47 Rachel Cole

If the patient does have decreased iron stores, that should be managed first before using other medications for RLS and IV Iron may also be used for some patients.

00:03:59 Rachel Cole

And then beyond nondrug measures and iron supplementation, if the patient has more severe symptoms of RLS, say, the symptoms are very persistent, they're interfering with sleep or the daytime functioning of that patient or leaning to symptoms such as anxiety or depression, then medication may be tried.

00:04:20 Rachel Cole

For many years there have been 2 main classes of medications that were typically recommended for restless leg syndrome. There are the dopaminergic meds or meds that work on dopaminergic receptors. The most common of which are pramipexole ropinirole and the rotigotine patch. And then there are GABA-ergic.

00:04:40 Rachel Cole

meds or GABA analogs and that included gabapentin and pregabalin or Lyrica.

00:04:48 Rachel Cole

And both of these classes of medications helped to decrease the urge to move the limbs, and both seem to have similar efficacy.

00:04:57 Rachel Cole

So at least one in five patients have at least a 50% decrease in symptoms with these medications.

00:05:03 Rachel Cole

Previous to the latest guidelines, either of these classes of meds was recommended depending on patient needs and preference.

00:05:12 Rachel Cole

Now, because more data is available on the long-term effects of dopaminergic agents, dopamine agonists like ropinirole are no longer first line for restless leg syndrome.

00:05:26 Rachel Cole

Prescribers typically reached for these to help RLS symptoms quickly, but now recent guidelines conditionally recommend against their use unless patients are prioritizing short term benefits over long term risks. And that's because evidence shows that these agents are linked to risk with long term use.

00:05:46 Rachel Cole

Including augmentation or the worsening of symptoms plus their side effects include compulsive behaviors, hallucinations, nausea and drowsiness. These meds may still have a place in the treatment of RLS for short term use, such as plane travel.

00:06:02 Rachel Cole

But they should be prescribed at the lowest effective dose.

00:06:08 Rachel Cole

So, evidence suggests a 20 to 30% prevalence of RLS augmentation with dopamine agonists and the risk increases as the dose increases. So again, what this looks like for the patient is a worsening of symptoms of RLS symptoms starting earlier, lasting longer or are more severe.

00:06:29 Rachel Cole

And the common response to worsening symptoms was to further increase the dose, but this further increases the risk of augmentation or the worsening of the symptoms.

00:06:39 Rachel Cole

When this happens, suggest switching to gabapentin or pregabalin, but never abruptly stop a dopamine agonist. You'll want to slowly taper off of the dopaminergic while titrating up the Gabaergic agent, and this will help prevent any rebound. Symptoms of RLS from discontinuing the dopamine agonist.

00:07:00 Rachel Cole

And do advise caution if you see prescriptions that are pushing up the doses of the dopaminergic agent because while this may provide improvement in the short term, increasing the dose can worsen the symptoms in the long run.

00:07:14 Rachel Cole

So, if symptoms persist after addressing exacerbating factors and iron deficiency, recommend Gabaergic agents like gabapentin or pregabalin, these meds improve disease severity and do not cause augmentation. They're also typically better tolerated than the dopaminergic agents.

00:07:35 Rachel Cole

They may be especially helpful for patients with anxiety, insomnia or pain.

00:07:40 Rachel Cole

Gabapentin and pregabalin usually take some time to be titrated up to an effective dose. They can cause some sedation and dizziness, so titration helps to improve tolerability. And for that reason, it can take patients longer to start seeing the effects of the Gabaergic meds.

00:07:59 Rachel Cole

One question that might come up is the difference between gabapentin and gabapentin enacarbil or HORIZANT, so gabapentin enacarbil is an extended-release form and pro drug of gabapentin, so we can't substitute one for the other. Gabapentin enacarbil is approved for restless leg syndrome.

00:08:19 Rachel Cole

And a difference is it doesn't have to be titrated like immediate release gabapentin, but it costs a few $100 a month.

00:08:27 Rachel Cole

As for other options, we want to save opioids as a last resort for short term use for more severe symptoms that don't respond to other treatments and don't suggest benzodiazepines, they don't have enough evidence of a benefit.

00:08:42 Rachel Cole

And we know that both of these classes of drugs can have other risks, like abuse and dependence.

00:08:50 Rachel Cole

So, we want to be listening for patients complaining of a worsening of symptoms of restless leg syndrome, especially if they've been on a dopaminergic Med for a while, or if you see the dose of the dopaminergic going up, that could be a clue to have a conversation with the patient about that concern of augmentation recommend getting iron.

00:09:11 Rachel Cole

Checked if the patient has not already done so, so any low iron stores can be.

00:09:16 Rachel Cole

addressed and look into possible exacerbating factors such as certain medications like antihistamines, statins, SSRIs, SNRIs and educate patients about other possible exacerbating factors such as alcohol, caffeine, untreated sleep apnea and smoking.

00:09:36 Rachel Cole

And if the decision is made to stop a dopamine agonist, these agents need to be tapered down gradually to lessen rebounds.

00:09:44 Rachel Cole

Symptoms and a Gabaergic Med can be titrated up while the dopaminergic is tapered down. Advise reserving dopamine agonists for selective short-term use such as plane travel and using these meds at the lowest effective dose.

00:10:01 Rachel Cole                                                          

And warn that pushing dopaminergic doses higher may improve symptoms short term but worsen symptoms in the long run.

00:10:09 Rachel Cole

And a note on gabapentin and gabapentin enacarbil don't auto sub these two meds since they are not the same gabapentin enacarbil is an extended-release formulation of the pro drug of gabapentin. It's pricier than plain gabapentin but does not require titration.

00:10:28 Rachel Cole

We have a couple of great resources online to help you compare oral and IV iron supplementation options to help address any low iron stores in patients with restless leg syndrome.

00:10:42 Narrator

We hope you enjoyed and gained practical insights from listening to this episode! 

00:10:46 Narrator

Now that you’ve listened, pharmacists and pharmacy technicians can receive CE credit. Just log into your Pharmacist’s Letter or Pharmacy Technician’s Letter account and look for the title of this podcast in the list of available CE courses.

00:10:59 Narrator

We’ve linked the resources we mentioned—and more on today’s topic—right in the show notes. Those links will take you straight to our websites, where you’ll find even more concise, evidence-based charts, articles, and tools.

00:11:12 Narrator

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00:11:31 Narrator

Also, be sure to explore our other TRC content—podcasts like Medication Talk and Rumor vs Truth, plus our full Pharmacy Essential Updates webinar series for deeper dives.

00:11:43 Narrator

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00:11:51 Narrator

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00:12:02 Narrator

Thanks for listening… stay sharp, stay current—and we’ll catch you next time on Clinical Capsules!