The American Academy of Neurology (AAN) has published evidence-based recommendations for management of restless legs syndrome (RLS) in adults. The practice guideline was published online ahead of print November 16, 2016, in Neurology. The practice guideline addresses the question: What are safe and effective therapies, including both pharmacologic and nonpharmacologic approaches, for the symptoms and clinical consequences (eg, disturbed sleep, periodic limb movements in sleep, depression/anxiety, and decreased quality of life) of RLS in adults.
“When addressing RLS, clinicians and patients must first determine whether symptoms require treatment, the setting in which this practice guideline is relevant,” said John W. Winkelman, MD, PhD, and colleagues. Dr. Winkelman is an Associate Professor of Psychiatry at Harvard Medical School and Medical Director of the Sleep Health Center of Brigham and Women’s Hospital in Boston.
John W. Winkelman, MD, PhD
“Treatment should be considered if RLS symptoms interfere with sleep or daytime function to an important degree,” the guideline authors said. “Before determining the best treatment, it is important to first ensure there are no contributing factors to RLS symptoms (eg, iron deficiency or serotonergic antidepressants). The guidelines advise clinicians to consider prescribing a pharmacologic agent to reduce RLS symptoms in patients with moderate to severe primary RLS. There is strong (Level A) evidence for use of pramipexole, rotigotine, cabergoline, and gabapentin enacarbil; moderate evidence (Level B) supports ropinirole, pregabalin, and IV ferric carboxymaltose; and weak evidence (Level C) supports levodopa. When considering efficacy alone, clinicians may prefer cabergoline. It is rarely used in clinical practice for RLS, however, because it is associated with a risk of cardiac valvulopathy. Clinicians are also advised to consider the augmentation risks associated with dopaminergic agents.
For patients with periodic limb movement disorder, there is strong (Level A) evidence supporting ropinirole. Moderate evidence (Level B) supports pramipexole, rotigotine, cabergoline, and pregabalin; and weak evidence (Level C) supporting levodopa. The authors note insufficient evidence (Level U) for gabapentin enacarbil and ferric carboxymaltose. With regard to objective sleep measures (eg, total sleep time, sleep efficiency, sleep latency, wake after sleep onset) there is moderate evidence (Level B) supporting ropinirole, gabapentin, encarbil, and pregabalin. However, there is insufficient evidence (Level U) supporting pamipexole, rotigotine, cabergoline, or levodopa.
For subjective sleep measures, cabergoline and gabapentin enacarbil have Level A evidence; ropinirole, pramipexole, rotigotine, and pregabalin have Level B evidence; and levodopa and prolonged-release oxycodone/naloxone, and vibratory stimulation have Level C evidence. Insufficient evidence (Level U) exists for ferric carboxymaltose and iron sucrose.When patients with RLS fail to respond to other treatments, clinicians are advised to consider prescribing prolonged-release oxycodone/naloxone (Level C) or to consider nonpharmacologic options, including pneumatic compression (Level B), infrared spectroscopy or transcranial magnetic stimulation (Level C), and vibrating pads (Level C).
For iron-deficient patients with RLS (ferritin levels ≤ 75 µg/L), clinicians are advised to prescribe ferrous sulfate with vitamin C. In patients on hemodialysis with secondary RLS, clinicians are advised to prescribe vitamin C and E supplementation (Level B), ropinirole, levodopa, or exercise (Level C).
—Erica Tricarico
Suggested Reading
Winkelman JW, Armstrong MJ, Allen RP, et al. Practice guideline summary: treatment of restless legs syndrome in adults: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2016 Nov 16 [Epub ahead of print].