Addressing Augmentation in Restless Leg Syndrome

September 20, 2018

The RLS expert explained his best practices for treating patients who develop augmentation after treatment.

Mark J. Buchfuhrer, MD

Current estimates suggest that restless leg syndrome (RLS) impacts almost 10% of the adult population, and although it is much more recognizable than it was a decade ago, major challenges still exist.

According to Mark J. Buchfuhrer, MD, a nationally recognized expert in RLS who has authored books and papers on the subject, the current trends in treatment have led to an increase in augmentation, a worsening of symptoms that occurs post-medication for the condition.

To gain further insight into the landscape of available treatments for RLS, and how to address augmentation when it appears, NeurologyLive spoke with Buchfuhrer in an interview.

NeurologyLive: What’s the current therapeutic landscape look like for restless leg syndrome?

Mark J. Buchfuhrer, MD: Currently, there are 4 approved drugs. There’s the 2 oldest are the short-acting dopamine agonists pramipexole (Mirapex) and ropinirole hydrochloride (Requip). They got approved in 2005-2006 for RLS, and they’re probably the most commonly prescribed drugs because they’re also generic and the companies that promoted them were still available with branded drugs and did a very good job. Most doctors, including neurologists, use this as first-line drugs mostly.

The other 2 drugs that are available are a long-acting dopamine agonist, the rotigotine transdermal patch (Neupro), which is FDA approved, and Horizant, a pre-drug of gabapentin, which of course is used a lot by neurologists and other doctors. That’s also long acting. Those 2 drugs are not used as much just because doctors don’t know them as well, they’re also much more expensive, and sometimes harder to get approved even when they are covered.

Are there any major challenges in treating RLS?

This is kind of interesting because the worst cases that I see in RLS come from treatment by a neurologist. That may sound kind of a little strange, but here’s what happens.

The key problem that we’re seeing now with the treatment of RLS is a condition called augmentation. What that is, is you treat with a dopamine agonist—especially a short-acting dopamine agonist, like Mirapex and Requip—and initially probably over 90% of patients respond to these drugs, which is why they got such quick acceptance and usage because they work really well, but 7% to 8% of patients per year that you put on these medications will start to get a worsening of RLS called augmentation. By 10 years, 70% to 80% or more of your patients will be in augmentation. I can’t say 100%, but probably, if you follow these patients for 10 or 15 years or more, you’ll probably see 90% of the patients develop a worsening of RLS requiring more and more medication which then makes the condition even worse.

The reason why I get my worst cases from neurologists is because they’re very comfortable using the short-acting dopamine agonists drugs in very high doses in Parkinson’s disease, and many of them don’t understand, or just don’t realize, you’re not supposed to use them in those high doses for RLS. In fact, the highest dose recommended in the FDA approval of RLS is 0.5 mg for Mirapex, and I can tell you that I commonly see patients on 1 mg, 1.5 mg, 2 mg—even up to 6 mg. The higher the dose, the more likely the augmentation is to occur, and the harder it is to treat when you see patients on those doses.

Currently, the biggest challenge that I see in restless legs is preventing and treating augmentation. In fact, I’m 1 of the authors of a consensus paper written by 13 of us, which, in its title, has the prevention and treatment of augmentation.

How do you approach treatment for augmentation?

There are different ways of treating the augmentation. If they’re on a small dose of the short-acting dopamine agonist, the first thing we recommend is don’t increase the dose. Patients will usually tell you, “Before I got treated I had restless legs at bedtime and I took the medication, and now I’m starting to get restless legs at 8 o’clock in the evening and I’ve never had it then. I can’t sit and watch TV.” Most doctors will say to take an extra dose earlier, but instead, we recommend to give the total dose earlier or split the dose: half earlier, half later. That’s the first thing they can do—not to increase the dose.

The other thing they can do is to maybe add another drug, like gabapentin or pregabalin (Lyrica) to avoid increasing the dose. We have an algorithm on this. Typically, we’ll say you can increase it once, but my personal recommendation is don’t even do that because then you’re pushing the patient on the road to augmentation when they’ve already displayed some evidence that they’re augmenting.

The other options you have are to change them to a long-acting dopamine agonist drug like the Neupro patch. There’s also—though it’s not approved for RLS—but long-acting Mirapex ER, extended release. How good of an option one of those is in an augmented patient still remains to be determined, but that may be helpful and possibly buy you some time. Another thing we suggest, rather than even adding gabapentin, is trying to switch to gabapentin or Horizant, at a low dose where you may have a chance. At higher dose it becomes very difficult because when you have a higher the dose of the short-acting dopamine agonist, when you try to stop it, the patient’s RLS just goes crazy for a couple weeks and they may not even sleep a minute. It’s hard not to get patients through that.

Transcript edited for clarity.