RLS Treatment – Clinical Practice Pearls

Restless Legs Syndrome (RLS) can be very debilitating for patients. It is a condition that often warrants pharmacotherapy. But which medications are most effective and how should we choose? I’ll lay out some of the most important RLS treatment clinical pearls in this blog post.

Dopamine Agonists Or Gabapentinoids For RLS?

I remember a time when clinicians typically first selected dopamine agonists as first-line therapy for RLS without hesitation. The preferred medication of choice according to this Mayo Clinic review is gabapentin or pregabalin. Second-line agents are considered to be dopamine agonists. There is some nuance with this recommendation in clinical practice making it reasonable to select a dopamine agonist over a gabapentinoid.

Gabapentin and pregabalin (alpha-2-delta-ligands) do have a few precautions that I would recommend considering. In geriatrics, for example, if patients are already sedated, dizzy, or have a history of falls, one might consider selecting dopamine agonists as first-line therapy. Another concern with gabapentin and pregabalin is the drug interaction with opioids. If you have a patient taking opioid therapy already for another condition, recall that these agents significantly increase the risk for respiratory depression. Patients with weight gain risks, fluid retention, and addiction risks may also be concerns with the use of gabapentin or pregabalin.

Gabapentin or Pregabalin in RLS?

In my experience, most clinicians will select gabapentin over pregabalin. I don’t have a great reason for that, but I would anticipate that most providers are more comfortable with prescribing gabapentin.

FF = Ferritin First

The MOST important assessment BEFORE beginning therapy for RLS is to assess iron stores. From that same Mayo Clinic review, target a ferritin of 75mg/L.

“If serum ferritin concentration is 75 mg/L and transferrin saturation is <45%, administer
an oral iron preparation (elemental iron 65 mg) with 100 to 200 mg of vitamin C every 1
or 2 days on an empty stomach. (Note that in the presence of inflammation or malignant
disease, serum ferritin concentration may be misleadingly high, and thus transferrin
saturation <20% may be a more accurate measure of iron deficiency.)”
The Management of Restless Legs Syndrome: An Updated Algorithm

Ropinirole Versus Pramipexole

I’ve spent some time comparing these agents in the past in this must read article. Important considerations when selecting between ropinirole versus pramipexole include CYP enzyme interactions and renal function. Here’s a link to that article to help differentiate some meaningful clinical differences.

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