RESTLESS legs syndrome (RLS) and periodic limb movement disorder (PLMD) are common neurologic sleep-related conditions that affect millions of adults and children in the United States. A newly published clinical practice guideline provides the most comprehensive treatment recommendations to date for these disorders, based on systematic evidence review and expert consensus.
The guideline, developed by a task force of sleep medicine experts and approved by the Board of Directors, offers strong or conditional recommendations across 27 treatment approaches for adults, special populations such as those with end-stage renal disease, and pediatric patients. It emphasizes the importance of regular iron status testing for all patients with clinically significant RLS, with specific thresholds guiding oral or intravenous supplementation strategies. Ferritin and transferrin saturation levels are central to these decisions, and pre-testing preparation—including a 24-hour avoidance of iron-rich foods or supplements—is advised.
For adults with RLS, the strongest recommendations support the use of gabapentinoids, including gabapentin enacarbil, gabapentin, and pregabalin, as well as intravenous ferric carboxymaltose in patients with iron deficiency. Additional therapies, such as ferrous sulfate, low-molecular-weight iron dextran, and dipyridamole, carry conditional endorsements based on lower certainty evidence.
Importantly, the guideline suggests avoiding standard use of several dopamine agonists and other agents, including levodopa, ropinirole, and pramipexole, due to risks of long-term side effects such as augmentation. The document also discourages use of medications like bupropion, carbamazepine, and clonazepam, citing low efficacy or insufficient evidence.
In patients with comorbid conditions like end-stage renal disease, the recommendations adjust accordingly, with careful suggestions for gabapentin, vitamin C, and IV iron sucrose depending on iron parameters.
This comprehensive guideline offers a critical tool for healthcare professionals navigating the nuanced treatment of RLS and PLMD across diverse patient populations.
Reference:
Winkelman JW. Treatment of restless legs syndrome and periodic limb movement disorder: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2025;21(1):137-52.
