A Clinical Review of the 2025 Restless Leg Syndrome Guidelines

Restless Legs Syndrome (RLS) and periodic limb movement disorder (PLMD), which affect nearly 5-10% of adults, are common with significant impacts on sleep quality, daily functioning, and overall quality of life. Published in Sleep Medicine, the recently updated RLS Guidelines provide accurate, evidence based clinical practice recommendations for the treatment of RLS and periodic limb movement disorder (PLMD) in both adults and pediatric populations.¹

To most accurately guide clinical decision making, the American Academy of Sleep Medicine (AASM) commissioned a task force of sleep medicine experts who developed the recommendations and assigned strength ratings based on a systematic review of the literature. Using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, the task force considered factors such as certainty of evidence, the balance of benefits and harms, patient values and preferences, and resource use. Once complete, the final recommendations were approved by the AASM Board of Directors. The updates follow the 2012 revisions to the RLS guidelines, incorporating new studies and emerging data relevant to RLS care.

The latest guidelines covered a broad spectrum of RLS management, beginning with diagnostic testing, treatment strategies, and symptom management, while highlighting populations in which RLS is particularly prevalent. The guidelines then provide recommendations for treating RLS, followed by specific treatment options tailored to individualized patient scenarios. These recommendations address adults, specialized adult populations, and children with RLS, as well as adults with PLMD.

Andy Berkowski, MD, PhD, board-certified by the American Board of Psychiatry and Neurology in Sleep Medicine, was part of the AASM task force asked to revamp the RLS guidelines. As part of ongoing coverage, NeurologyLive^® sat down with Berkowski for an exclusive interview about the key points of the new guidelines, as well as the clinical significance of some of the finer recommendations. Berkowski, founder of ReLACS Health, also highlighted unanswered questions and potential gaps within the guidelines while sharing his perspective on the future of RLS care following their implementation.

Guideline Overview:

The 2025 RLS guidelines represent a major shift in treatment strategy compared to prior iterations. Overall, the focus has moved away from dopamine agonists, which were historically first-line therapy, toward iron supplementation and gabapentinoid medications. This transition reflects years of accumulating evidence and a growing understanding of RLS pathophysiology. While dopamine agonists are still occasionally indicated in rare cases, they are generally no longer recommended.

Key Takeaways:

• Dopamine agonists, once first-line, are no longer recommended except in rare circumstances.
• Primary focus should be on iron management and gabapentinoids.
• This represents a 180-degree reversal from the 2012 guidelines.
• Clinicians will need to adjust prescribing habits to align with updated evidence.

Clinical Implications on Patient Care:

The updated guidelines emphasize a preventative, individualized approach. Clinicians are encouraged to optimize sleep hygiene and minimize RLS-exacerbating factors before initiating pharmacologic therapy. Assessment and management of iron levels is central to care, with specific serum targets recommended for both oral and intravenous supplementation. This approach aims to stabilize symptoms, reduce disease progression, and limit medication-related complications.

Key Takeaways:

• Preventative care: Prioritize sleep hygiene, consistent sleep patterns, and avoidance of substances that exacerbate RLS (alcohol, certain antidepressants, antiemetics, antipsychotics).
• Iron evaluation: Regular monitoring of ferritin and transferrin saturation is essential.
  • Oral iron: ferritin <75 or transferrin saturation <20%
  • IV iron: ferritin up to 100
• Focus on individualized treatment planning beyond general recommendations.
• Emphasizes early intervention and symptom prevention rather than reactive treatment.

Unanswered Questions:

While the 2025 guidelines provide strong evidence-based recommendations for first-line treatment, Berkowski noted that they leave some questions unresolved, particularly regarding second- or third-line therapies. Of note, clinicians must still exercise judgment for patients who fail initial treatments. Opioids and dopamine agonists remain areas of clinical uncertainty, with opioids conditionally recommended and dopamine agonists generally discouraged. The guidelines serve as a framework rather than a comprehensive stepwise algorithm for complex cases.

Key Takeaways:

• Guidelines focus on first-line treatment, leaving less guidance for patients who fail multiple therapies.
• Dopamine agonists: generally recommended against, though short-term or specific-use cases exist.
• Opioids: conditionally recommended, but require careful clinical judgment.
• Provides a general framework rather than detailed hierarchy for second- and third-line therapy.

Future Implications For the Field:

All told, Berkowski emphasized that the 2025 guidelines mark a paradigm shift in RLS management. By removing dopamine agonists from routine care, clinicians are expected to adopt a preventative, iron-focused strategy. This shift may lead to fewer cases of augmentation (symptom worsening due to dopamine agonist use) and improved long-term patient outcomes. The new approach aims to change RLS from a perceived chronic, worsening condition to one that is manageable and stable for many patients, benefiting primary care, neurology, and sleep medicine providers.

Key Takeaways:

• Major paradigm shift: Dopamine agonists largely removed from routine care.
• Emphasis on preventative care and management of exacerbating factors.
• Iron supplementation and gabapentinoids are now mainstay treatments.
• Anticipated outcomes: more stable symptoms, reduced augmentation, and improved long-term management.
• Potential to change perception of RLS from a degenerative condition to a manageable disorder.

Transcript edited for clarity.

REFERENCE
1. Winkelman JW, Berkowski JA, DelRosso LM, et al. 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):137-152. doi:10.5664/jcsm.11390