Treatment of Restless Legs Syndrome and Periodic Limb Movement Disorder

Publication Date: September 26, 2024
Last Updated: November 12, 2024

Good Practice Statements

  • In all patients with clinically significant restless legs syndrome (RLS), clinicians should regularly test serum iron studies including ferritin and transferrin saturation (calculated from iron and total iron binding capacity). The test should ideally be administered in the morning avoiding all iron-containing supplements and foods at least 24 hours prior to blood draw.
  • Analysis of iron studies greatly influences the decision to use oral or intravenous (IV) iron treatment.
  • Consensus guidelines, which have not been empirically tested, suggest that supplementation of iron in adults with RLS should be instituted with oral or IV iron if serum ferritin ≤75 ng/mL or transferrin saturation < 20%, and only with IV iron if serum ferritin is between 75 ng/mL and 100 ng/mL.
  • In children, supplementation of iron should be instituted for serum ferritin < 50 ng/mL with oral or IV formulations. These iron supplementation guidelines are different than for the general population.
  • The first step in the management of RLS should be addressing exacerbating factors, such as alcohol, caffeine, antihistaminergic, serotonergic, anti-dopaminergic medications, and untreated obstructive sleep apnea.
  • RLS is common in pregnancy; prescribers should consider the pregnancy-specific safety profile of each treatment being considered.

Adults with Restless Legs Syndrome

In adults with RLS, the AASM recommends the use of gabapentin enacarbil over no gabapentin enacarbil. (S, M )
620
In adults with RLS, the AASM recommends the use of gabapentin over no gabapentin. (S, M )
620
In adults with RLS, the AASM recommends the use of pregabalin over no pregabalin. (S, M )
620
In adults with RLS, the AASM recommends the use of IV ferric carboxymaltose over no IV ferric carboxymaltose in patients with appropriate iron status. (S, M )
620
In adults with RLS, the AASM suggests the use of IV low molecular weight iron dextran over no IV low molecular weigh iron dextran in patients with appropriate iron status. (C, VL )
620
Recommendation 6: In adults with RLS, the AASM suggests the use of IV ferumoxytol over no IV ferumoxytol in patients with appropriate iron status. (C, VL )
620
In adults with RLS, the AASM suggests the use of ferrous sulfate over no ferrous sulfate in patients with appropriate iron status. (C, M )
620
In adults with RLS, the AASM suggests the use of dipyridamole over no dipyridamole. (C, L )
620
In adults with RLS, the AASM suggests the use of extended-release oxycodone and other opioids over no opioids. (C, M )
620
In adults with RLS, the AASM suggests the use of bilateral high-frequency peroneal nerve stimulation over no peroneal nerve stimulation. (C, L )
620
In adults with RLS, the AASM suggests against the standard use of levodopa. (C, VL )
Remarks: Levodopa may be used to treat RLS in patients who place a higher value on the reduction of restless legs symptoms with short-term use and a lower value on adverse effects with long-term use (particularly augmentation).
620
In adults with RLS, the AASM suggests against the standard use of pramipexole. (C, M )

Remarks: Pramipexole may be used to treat RLS in patients who place a higher value on the reduction of restless legs symptoms with short-term use and a lower value on adverse effects with long-term use (particularly augmentation).

620
In adults with RLS, the AASM suggests against the standard use of transdermal rotigotine. (C, L )
Remarks: Transdermal Rotigotine may be used to treat RLS in patients who place a higher value on the reduction of restless legs symptoms with short-term use and a lower value on adverse effects with long-term use (particularly augmentation).
620
In adults with RLS, the AASM suggests against the standard use of ropinirole. (C, M )
Remarks: Ropinirole may be used to treat RLS in patients who place a higher value on the reduction of restless legs symptoms with short-term use and a lower value on adverse effects with long-term use (particularly augmentation).
620
In adults with RLS, the AASM suggests against the use of bupropion for the treatment of RLS. (C, M )
620
In adults with RLS, the AASM suggests against the use of carbamazepine. (C, L )
620
In adults with RLS, the AASM suggests against the use of clonazepam. (C, VL )
620
In adults with RLS, the AASM suggests against the use of valerian. (C, L )
620
In adults with RLS, the AASM suggests against the use of valproic acid. (C, L )
620
In adults with RLS, the AASM recommends against the use of cabergoline. (S, M )
620

Special Populations with Restless Legs Syndrome

In adults with RLS and end-stage renal disease (ESRD), the AASM suggests the use of gabapentin over no gabapentin. (C, VL )
620
In adults with RLS and ESRD, the AASM suggests the use of IV iron sucrose over no IV iron sucrose in patients with ferritin < 200 ng/mL and transferrin saturation < 20%. (C, M )
620
In adults with RLS and ESRD, the AASM suggests the use of vitamin C over no vitamin C. (C, L )
620
In adults with RLS and ESRD, the AASM suggests against the standard use of levodopa. (C, L )

Remarks: Levodopa may be used to treat RLS in patients who place a higher value on the reduction of restless legs symptoms with short-term use and a lower value on adverse effects with long-term use (particularly augmentation).

620
In adults with RLS and ESRD, the AASM suggests against the standard use of rotigotine. (C, VL )
Remarks: Rotigotine may be used to treat RLS in patients who place a higher value on the reduction of restless legs symptoms with short-term use and a lower value on adverse effects with long-term use (particularly augmentation).
620

Adults with Periodic Limb Movement Disorder

In adults with PLMD, the AASM suggests against the use of triazolam. (C, VL )
620
In adults with PLMD, the AASM suggests against the use of valproic acid. (C, VL )
620

Children with Restless Legs Syndrome

In children with RLS, the AASM suggests the use of ferrous sulfate over no ferrous sulfate in patients with appropriate iron status. (C, VL )
620

Video

Recommendation Grading

Abbreviations

  • AASM:

    American Academy Of Sleep Medicine

  • ESRD:

    end-stage Renal Disease

  • IV: Intravenous
  • PLMD:

    periodic Limb Movement Disorder

  • RLS:

    restless Legs Syndrome

Overview

Title

Treatment of Restless Legs Syndrome and Periodic Limb Movement Disorder

Authoring Organization

American Academy of Sleep Medicine

Publication Month/Year

September 26, 2024

Last Updated Month/Year

October 1, 2024

Supplemental Implementation Tools

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Document Objectives

This guideline establishes clinical practice recommendations for Treatment of Restless Legs Syndrome (RLS) and Periodic Limb Movement Disorder (PLMD) in adults and pediatric patients.

Target Patient Population

Patients with restless legs syndrome / periodic limb movement disorder

Inclusion Criteria

Male, Female, Adolescent, Adult, Child, Older adult

Health Care Settings

Ambulatory, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Assessment and screening, Treatment, Management

Diseases/Conditions (MeSH)

D012148 - Restless Legs Syndrome, D009069 - Movement Disorders

Keywords

restless legs syndrome, periodic limb movement disorder

Source Citation

Winkelman JW, Berkowski JA, DelRosso LM, Koo BB, Scharf MT, Sharon D, Zak RS, Kazmi U, Falck-Ytter Y, Shelgikar AV, Trotti LM, Walters AS. Treatment of restless legs syndrome and periodic limb movement disorder: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2024 Sep 26. doi: 10.5664/jcsm.11390. Epub ahead of print. PMID: 39324694.