Your legs will not let you settle at night

What restless legs syndrome is

Restless legs syndrome is an urge to move the legs, usually with an uncomfortable sensation, that comes on at rest, is worse in the evening and at night, and is relieved at least temporarily by movement. It is a neurological condition, not a circulation problem and not “nerves”.

It is common in pregnancy, and it frequently coexists with periodic limb movements during sleep, which is a separate finding on a sleep study.

The guidance changed in 2025, and it changed direction

This matters more than it usually would, because the current guideline reverses what the previous one said.

The American Academy of Sleep Medicine published a new clinical practice guideline for restless legs syndrome and periodic limb movement disorder, accepted in September 2024 and carried in the January 2025 issue of the Journal of Clinical Sleep Medicine. It contains 28 recommendations and replaces the 2012 guideline.

The 2012 guideline strongly supported the dopamine agonists pramipexole and ropinirole. The 2025 guideline suggests against their standard use. If you have read an older page, or been given these medicines years ago and never reviewed, that is the single most important thing on this page.

Why the reversal

The reason is augmentation: a worsening caused by the treatment itself. Over months to years on dopaminergic therapy, symptoms can start earlier in the day, spread to other parts of the body, and become more intense. Short registration trials do not run long enough to show it, which is how these drugs came to be first-line in the first place.

The guideline does not ban them. It frames them as a values-sensitive exception: they may still suit someone who places a high value on short-term relief and a lower value on long-term adverse effects, particularly augmentation. That is a conversation, not a default.

What the 2025 guideline recommends

Strong recommendations for adults, all at moderate certainty of evidence:

• Gabapentin enacarbil. The only remaining FDA-approved drug for restless legs syndrome that carries a strong recommendation.
• Gabapentin.
• Pregabalin.
• Intravenous ferric carboxymaltose, in patients whose iron status is appropriate for it.

Conditionally supported: bilateral high-frequency peroneal nerve stimulation delivered by a wearable device, and low-dose extended-release oxycodone and other low-dose opioids, the latter with explicit caution and follow-up.

Suggested against

Alongside the dopamine agonists, the guideline suggests against transdermal rotigotine and against levodopa, and recommends against cabergoline outright on its harm profile. It also suggests against bupropion, carbamazepine, clonazepam, valerian and valproic acid, at varying levels of certainty.

Iron is part of the workup, not an afterthought

The guideline carries a good-practice statement that iron status should be evaluated in everyone with restless legs syndrome. Low brain iron is treated as an important mechanism of the condition rather than an incidental finding, which is why intravenous iron appears among the strong recommendations.

The first thing we look at

Before any prescription, the guideline’s own framing is to look for things that make restless legs worse. Alcohol, caffeine, some antidepressants, some antihistamines, and untreated obstructive sleep apnea are all on that list. Removing an aggravator is sometimes the whole answer, and it is always cheaper and safer than adding a drug.

What happens here

You are seen by Dr. Qadoom, who takes the history, reviews every medicine you are on for anything that could be aggravating the symptoms, and arranges iron studies. If you are already on a dopamine agonist, that gets reviewed against current guidance rather than simply renewed.

Sources

1. American Academy of Sleep Medicine clinical practice guideline for the treatment of restless legs syndrome and periodic limb movement disorder, Winkelman JW et al., Journal of Clinical Sleep Medicine, January 2025 issue. https://link.springer.com/article/10.5664/jcsm.11390
2. AASM, “New guideline provides treatment recommendations for restless legs syndrome”. https://aasm.org/new-guideline-provides-treatment-recommendations-for-restless-legs-syndrome/
3. AASM summary of the RLS and PLMD clinical practice guideline. https://aasm.org/summary-of-new-clinical-practice-guideline-for-rls-and-plmd/

Related pages

• Sleep apnea →
• Sleep testing, at home and in the lab →
• Cost, insurance and referrals →