New guideline provides treatment recommendations for restless legs syndrome

Available online as an accepted paper in the Journal of Clinical Sleep Medicine, the guideline updates the AASM's previous guidance published in 2012. The authors noted that numerous clinical trials and longitudinal studies have been conducted in the last decade, contributing vital evidence that supports these new recommendations.

"This new clinical practice guideline from the AASM represents an important turning point in the treatment of RLS in adults," said Dr. John Winkelman, chair of the AASM task force, professor of psychiatry at Harvard Medical School, and chief of the sleep disorders clinical research program at Massachusetts General Hospital. "Guided by the best evidence in the scientific literature, we've provided recommendations that will improve the ability of clinicians to provide patient-centered care for people who have RLS."

RLS is a sleep-related movement disorder characterized by a strong, nearly irresistible urge to move the legs, which is often accompanied by other uncomfortable sensations felt in the legs. These symptoms begin or worsen during periods of rest or inactivity, are temporarily or totally relieved by movement, and occur exclusively or predominantly in the evening or at night. RLS can cause sleep disturbance, distress, and impairment in functioning.

One of the significant changes in the new guideline is that it elevates the importance of iron evaluation in everyone with RLS and, depending on iron indices, recommends iron supplementation. These recommendations reflect evidence suggesting that low brain iron is an important underlying cause of RLS. For adults with RLS, the guideline provides a strong recommendation for intravenous ferric carboxymaltose and conditional recommendations for two other formulations of intravenous iron and one formulation of oral iron -- ferrous sulfate. For children with RLS, ferrous sulfate received a conditional recommendation, making it the only treatment recommended for pediatric patients.

A "strong" recommendation is one that clinicians should follow under most circumstances. A "conditional" recommendation reflects a lower degree of certainty and requires the clinician to use clinical judgment and consider the patient's values and preferences to determine the best course of action.

Another important change is that the new guideline includes conditional recommendations against the standard use of pramipexole and ropinirole, both of which were supported by strong recommendations in the 2012 guidance. Research published in the last 10 years has clarified that the long-term use of these dopamine agonists and other dopaminergic medications is often associated with the risk of "augmentation," which is the gradual worsening of RLS symptom intensity and duration.

In contrast, new evidence supporting three alpha-2-delta ligand calcium channel blockers -- gabapentin enacarbil, gabapentin, and pregabalin -- led the task force to support them as strong recommendations for RLS treatment. These medications are not associated with the augmentation of RLS symptoms observed with the dopaminergic agents.

Bilateral high-frequency peroneal nerve stimulation, an innovative treatment developed in the years since the previous guidance was published, received a conditional recommendation of support. Treatment involves the use of a wearable device to stimulate the nerves in the legs before bedtime.

The use of low-dose, extended-release oxycodone and other low-dose opioids also received conditional recommendations of support. The authors noted that low-dose opioids have demonstrated efficacy for RLS, but opioids also have risks that require cautious use and clinical oversight. A national RLS opioid registry based at Massachusetts General Hospital continues to collect longitudinal data to assess the long-term safety, dose stability, and efficacy of opioid medications for RLS.

The authors advised that the first step in the management of RLS should be to address exacerbating factors including alcohol, caffeine, certain antidepressant and antihistamine medications, and untreated obstructive sleep apnea. They also noted that RLS is common in pregnancy.

To develop the guideline, the AASM commissioned a task force of sleep medicine clinicians with expertise in RLS. They crafted 28 clinical practice recommendations based on a systematic review of the literature and an assessment of the evidence according to the GRADE process, taking into consideration the quality of evidence, beneficial and harmful effects, patient values and preferences, and resource use.