Three Important Changes in AASM’s New Restless Legs Syndrome Guidelines

The American Academy of Sleep Medicine (AASM) has updated its guidelines for the treatment of restless legs syndrome (RLS) for the first time in 12 years.

In this video interview, guideline author John Winkelman, MD, PhD, of Harvard Medical School and Massachusetts General Hospital in Boston, highlights the three key changes to the guidelines.

The following is a transcript of his remarks:

The American Academy of Sleep Medicine has not updated their restless legs syndrome guidelines since 2012.

They use a great methodology, with heavy emphasis on meta-analysis of clinical trials and balances the benefits of medications versus their short- and long-term side effects. The task force from the American Academy of Sleep Medicine, we worked on this for 5 years, meeting monthly, going over these meta-analyses in detail, and had a number of recommendations which are distinct from the guidelines from 12 years ago.

The most shocking, probably, change from 2012 is that the dopamine agonists, which are the primary first-line treatment for most healthcare practitioners for treating restless legs syndrome, we are now recommending against their standard use. Not because they don’t work in the short term, they do. They’re incredible in the short term. But over the long term, for most people, they make restless legs syndrome worse.

They do it slowly, so you don’t really notice for a year or 2. But insidiously, symptoms start happening earlier and earlier and earlier in the day. And then healthcare providers start redistributing the medication, increasing the dose, which only accelerates the problem. And over a period of many years, RLS becomes substantially a problem for 6, 8, 12, or 16 hours a day. Not only in terms of time, but in terms of body parts. It goes from the legs — no longer restless legs syndrome — and starts to affect the upper extremities, which are much harder for people to manage because you can’t just walk it off because it’s your arms.

So number one, we are now recommending against dopamine agonists as standard use.

Number two, the good news is that we have strongly recommended first-line treatments. Those are the alpha2-delta calcium channel ligands — that’s gabapentin [Neurontin], gabapentin enacarbil, and pregabalin [Lyrica]. A lot of new evidence over the last 12 years [shows] that these medications are extremely effective for RLS.

They can have side effects — usually those can be avoided if you start low and go slow — but at least the side effects are apparent early on. So evidence demonstrates that they work for RLS. They are as good as the dopamine agonists.

The third thing — good news — is that intravenous iron, it is now clear, is an effective treatment for restless legs syndrome in patients with a ferritin below 100 or transferrin saturation below 20%.

Why would IV iron be good for RLS? It’s because restless legs syndrome is a brain iron deficiency. If you look in the brains of people with RLS through a variety of imaging techniques, you’ll see that brain iron is low. Iron doesn’t passively diffuse into the brain; it’s actively transported. And there’s a problem with transport of iron into the brain that then, through basically unclear mechanisms, leads to restless legs syndrome. And if you give more IV iron, a lot of IV iron, or in people with really low iron you can give oral iron and push more iron into the system, into the brain, then you can get a reduction in RLS symptoms.

These new guidelines are important because when you look at prescriptions for restless legs syndrome in the United States — and I did in a recent study where I had 90% of all prescriptions available to me for people with RLS — 60% of people with RLS are getting a dopaminergic medication, which we know in a substantial percentage of them over a number of many years — 1, 3, 5, it could be 10 — is going to worsen their RLS.

This is the last thing that any provider wants for their patient, is to do something that’s making them worse, even if it’s great in the short term. Because RLS, for most people, is a long-term problem. You start treating somebody at 50, you gotta think about 40 years that you’re going to be treating them, and so you need to take that into account. If in 10 years it’s going to make things worse, you should at least warn the patient of the risk of this, number one. And number two, be constantly monitoring, trying to see if symptoms are moving earlier and moving from the legs up to the arms.

So it’s this awareness of augmentation that is really, I think, the most important part of these new guidelines.