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Introduction: This guideline establishes clinical practice recommendations for treatment of restless legs syndrome (RLS) and periodic limb movement disorder (PLMD) in adults and pediatric patients., Methods: The American Academy of Sleep Medicine (AASM) commissioned a task force of experts in sleep medicine to develop recommendations and assign strengths based on a systematic review of the literature and an assessment of the evidence using the grading of recommendations assessment, development, and evaluation methodology. The task force provided a summary of the relevant literature and the certainty of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations that support the recommendations. The AASM Board of Directors approved the final recommendations., Good Practice Statement: The following good practice statement is based on expert consensus, and its implementation is necessary for the appropriate and effective management of patients with RLS., 1. In all patients with clinically significant RLS, clinicians should regularly test serum iron studies including ferritin and transferrin saturation (calculated from iron and total iron binding capacity). Testing 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 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., 2. The first step in the management of RLS should be addressing exacerbating factors, such as alcohol, caffeine, antihistaminergic, serotonergic, antidopaminergic medications, and untreated obstructive sleep apnea., 3. RLS is common in pregnancy; prescribers should consider the pregnancy-specific safety profile of each treatment being considered., Recommendations: The following recommendations are intended as a guide for clinicians in choosing a specific treatment for RLS and PLMD in adults and children. Each recommendation statement is assigned a strength ("strong" or "conditional"). A "strong" recommendation (ie, "We recommend…") is one that clinicians should follow under most circumstances. The recommendations listed below are ranked in the order of strength of recommendations and grouped by class of treatments within each PICO (Patient, Intervention, Comparator, Outcome) question. Some recommendations include remarks that provide additional context to guide clinicians with implementation of this recommendation., Adults With Rls: 1. In adults with RLS, the AASM recommends the use of gabapentin enacarbil over no gabapentin enacarbil (strong recommendation, moderate certainty of evidence)., 2. In adults with RLS, the AASM recommends the use of gabapentin over no gabapentin (strong recommendation, moderate certainty of evidence)., 3. In adults with RLS, the AASM recommends the use of pregabalin over no pregabalin (strong recommendation, moderate certainty of evidence)., 4. In adults with RLS, the AASM recommends the use of IV ferric carboxymaltose over no IV ferric carboxymaltose in patients with appropriate iron status (see good practice statement for iron parameters) (strong recommendation, moderate certainty of evidence)., 5. In adults with RLS, the AASM suggests the use of IV low molecular weight iron dextran over no IV low molecular weight iron dextran in patients with appropriate iron status (see good practice statement for iron parameters) (conditional recommendation, very low certainty of evidence)., 6. In adults with RLS, the AASM suggests the use of IV ferumoxytol over no IV ferumoxytol in patients with appropriate iron status (see good practice statement for iron parameters) (conditional recommendation, very low certainty of evidence)., 7. In adults with RLS, the AASM suggests the use of ferrous sulfate over no ferrous sulfate in patients with appropriate iron status (see good practice statement for iron parameters) (conditional recommendation, moderate certainty of evidence)., 8. In adults with RLS, the AASM suggests the use of dipyridamole over no dipyridamole (conditional recommendation, low certainty of evidence)., 9. In adults with RLS, the AASM suggests the use of extended-release oxycodone and other opioids over no opioids (conditional recommendation, moderate certainty of evidence)., 10. In adults with RLS, the AASM suggests the use of bilateral high-frequency peroneal nerve stimulation over no peroneal nerve stimulation (conditional recommendation, moderate certainty of evidence)., 11. In adults with RLS, the AASM suggests against the standard use of levodopa (conditional recommendation, very low certainty of evidence)., 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)., 12. In adults with RLS, the AASM suggests against the standard use of pramipexole (conditional recommendation, moderate certainty of evidence)., 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)., 13. In adults with RLS, the AASM suggests against the standard use of transdermal rotigotine (conditional recommendation, low certainty of evidence)., 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)., 14. In adults with RLS, the AASM suggests against the standard use of ropinirole (conditional recommendation, moderate certainty of evidence)., 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)., 15. In adults with RLS, the AASM suggests against the use of bupropion for the treatment of RLS (conditional recommendation, moderate certainty of evidence)., 16. In adults with RLS, the AASM suggests against the use of carbamazepine (conditional recommendation, low certainty of evidence)., 17. In adults with RLS, the AASM suggests against the use of clonazepam (conditional recommendation, very low certainty of evidence)., 18. In adults with RLS, the AASM suggests against the use of valerian (conditional recommendation, very low certainty of evidence)., 19. In adults with RLS, the AASM suggests against the use of valproic acid (conditional recommendation, low certainty of evidence)., 20. In adults with RLS, the AASM recommends against the use of cabergoline (strong recommendation, moderate certainty of evidence)., Special Adult Populations With Rls: 21. In adults with RLS and end-stage renal disease (ESRD), the AASM suggests the use of gabapentin over no gabapentin (conditional recommendation, very low certainty of evidence)., 22. 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% (conditional recommendation, moderate certainty of evidence)., 23. In adults with RLS and ESRD, the AASM suggests the use of vitamin C over no vitamin C (conditional recommendation, low certainty of evidence)., 24. In adults with RLS and ESRD, the AASM suggests against the standard use of levodopa (conditional recommendation, low certainty of evidence)., 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)., 25. In adults with RLS and ESRD, the AASM suggests against the standard use of rotigotine (conditional recommendation, very low certainty of evidence)., 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)., Adults With Plmd: 26. In adults with PLMD, the AASM suggests against the use of triazolam (conditional recommendation, very low certainty of evidence)., 27. In adults with PLMD, the AASM suggests against the use of valproic acid (conditional recommendation, very low certainty of evidence)., Children With Rls: 28. In children with RLS, the AASM suggests the use of ferrous sulfate over no ferrous sulfate in patients with appropriate iron status (see good practice statement for iron parameters) (conditional recommendation, very low certainty of evidence)., Citation: 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., (© 2025 American Academy of Sleep Medicine.)

Introduction: This systematic review provides supporting evidence for the accompanying clinical practice guideline on the treatment of restless legs syndrome and periodic limb movement disorder., Methods: The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine. A systematic review was conducted to identify studies that compared the use of pharmacological or nonpharmacological treatment to no treatment to improve patient-important outcomes. Statistical analyses were performed to determine the clinical significance of using various interventions to treat restless legs syndrome and periodic limb movement disorder in adults and children. The Grading of Recommendations Assessment, Development, and Evaluation process was used to assess the evidence for making recommendations., Results: The literature search resulted in 3,631 studies out of which 148 studies provided data suitable for statistical analyses. The task force provided a detailed summary of the evidence along with the certainty of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations., Citation: Winkelman JW, Berkowski JA, DelRosso LM, et al. Treatment of restless legs syndrome and periodic limb movement disorder: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med . 2025;21(1):153-199., (© 2025 American Academy of Sleep Medicine.)

Study Objectives: To assess the seasonality of restless legs syndrome (RLS) using data from the Korean national health insurance database., Methods: We retrospectively reviewed a randomly selected sample representing 3% of the national health insurance claims database in South Korea. From this sample, we obtained the monthly numbers of patients with RLS and diagnoses from 2009 to 2016, along with prescriptions for monthly dopamine agonists and clonazepam for patients with RLS from 2009 to 2013. Total dopamine agonist and clonazepam doses were converted to levodopa-equivalent doses, and the monthly cumulative prescription dose was calculated. Cosinor analysis was used to evaluate the seasonal pattern of each variable., Results: This study included 11,466 patients with RLS and their diagnoses and 4,887 prescriptions for dopamine agonists and clonazepam. There were significant seasonal patterns in the numbers of patients with RLS (P < .001) and diagnoses (P < .001), both of which peaked in August. The magnitude of the greatest difference in the number of patients with RLS between August (highest) and February (lowest) was 29.96% (95% confidence interval, 24.03-100.80), and that of the number of RLS diagnoses was 39.56% (95% confidence interval, 31.24-47.89). The cumulative prescription dose of medication showed no significant seasonality., Conclusions: Our findings suggest that the prevalence of RLS is seasonally affected, with an increase during summer., (© 2021 American Academy of Sleep Medicine.)

Study Objectives: To estimate the association of restless legs syndrome (RLS) and its frequency with sleep-wake disturbances in pregnancy., Methods: A cohort of 1,563 women in their third trimester of pregnancy were recruited from prenatal clinics between March 2007 and December 2010. Demographic, pregnancy, and delivery data were extracted from medical records and sleep information was collected with questionnaires. To diagnose RLS, we used standardized criteria of RLS symptoms and frequency that were developed by the International Restless Legs Study Group. Logistic regression models were constructed to investigate the association of RLS and its frequency with sleep-wake disturbances (poor sleep quality, daytime sleepiness, poor daytime function) and delivery outcomes., Results: Overall 36% of the pregnant women had RLS, and half had moderate to severe symptoms. Compared to women without RLS, those with RLS were more likely to have poor sleep quality (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.7-2.9), poor daytime function (OR 1.9, 95% CI 1.4-2.4), and excessive daytime sleepiness (OR 1.6, 95% CI 1.3-2.0). A dose-response relationship also was evident between RLS frequency and each of the sleep-wake disturbances. There was no evidence for any association between RLS and delivery outcomes., Conclusions: RLS is a significant contributor to poor sleep quality, daytime sleepiness, and poor daytime function, all common and often debilitating conditions in pregnancy. Obstetric health care providers should be aware of these associations and screen women for RLS., Commentary: A commentary on this article appears in this issue on page 857., (© 2017 American Academy of Sleep Medicine)

Study Objectives: To determine the depth and distribution of sensory discomfort in idiopathic restless legs syndrome/Willis-Ekbom disease (RLS) and RLS concurrent with other leg conditions, specifically peripheral neuropathy, sciatica, leg cramps, and arthritis., Methods: RLS subjects (n = 122) were divided into 71 idiopathic RLS and 51 RLS-C, or Comorbid, groups. All subjects were examined by an RLS expert, answered standardized RLS questionnaires, and received a body diagram to draw the location and depth of their symptoms., Results: Age was 63.04 ± 12.84 years, with 77 females and 45 males. All patients had lower limb involvement and 43/122 (35.25%) also had upper limb involvement. Of the 122 subjects, 42.62% felt that the RLS discomfort was only deep, 9.84% felt that the discomfort was only superficial, and 47.54% felt both superficial and deep discomfort. There were no defining characteristics in depth or distribution of RLS sensations that differentiated those patients with idiopathic RLS from those patients with RLS associated with other comorbid leg conditions. The sensation of arthritis was felt almost exclusively in the joints and not in the four quadrants of the leg, whereas the exact opposite was true of RLS sensations., Conclusions: Depth and distribution cannot be used as a discriminative mechanism to separate out idiopathic RLS from RLS comorbid with other leg conditions. Although seen in clinical practice, the total absence of patients with non-painful RLS only in the joints in the current study attests to the rarity of this presentation and raises the possibility of misdiagnosis under these circumstances. We recommend that such patients not be admitted to genetic or epidemiological studies., (© 2016 American Academy of Sleep Medicine)

Objectives: Restless legs syndrome (RLS) is a burdensome sensorimotor disorder that has been linked to diabetes and obesity. However, the relationship of RLS to gestational diabetes mellitus (GDM), a common pregnancy complication strongly associated with obesity and a harbinger of diabetes, remains unknown. In this study, we examined the association of RLS to history of GDM in a sample of older female primary care patients., Methods: Participants were community-dwelling women aged ≥ 40 years drawn from an anonymous survey study of West Virginia adult primary care patients. Data gathered included detailed information on demographics, lifestyle factors, reproductive history, sleep patterns, and medical history; the survey also included an RLS diagnostic questionnaire. Women who were pregnant or had missing data on key variables were excluded from the analyses., Results: Of the 498 participants included in the final analytic sample, 24.5% met diagnostic criteria for RLS (17.9% with symptoms at least once/week). After adjustment for demographics, lifestyle characteristics, body mass index, diabetes and other comorbid conditions, parity, and other factors, those reporting history of GDM were almost three times as likely to meet criteria for RLS (odds ratio [OR] = 2.7, 95% confidence interval [CI] = 1.3, 5.3). This association increased in magnitude with increasing symptom frequency (adjusted OR for RLS symptoms ≥ 3×/week = 4.8, CI 2.1, 11.2, p for trend = 0.004)., Conclusions: History of GDM was strongly and positively related to RLS in this study of older female primary care patients, offering further support for a possible role of metabolic dysregulation in RLS development., (© 2015 American Academy of Sleep Medicine.)

Objectives: Over the last decade therapeutic, pathogenetic, epidemiological and genetic research in restless legs syndrome/Willis-Ekbom Disease (RLS/WED) has required the development of specific quality of life scales and sleep scales. A Movement Disorder Society Task Force formally evaluated the quality of these scales., Methods: A literature search retrieved 5 quality of life instruments specific to RLS. As per MDS protocol, each scale was evaluated by 3 criteria which included (a) use in RLS, (b) use by research or clinical groups other than the group that developed the scale, and (c) formal validation and adequate clinimetric properties. Scales were categorized as "Recommended" when all 3 criteria were met, "Suggested" when used for RLS but only one of the other criteria was met, and "Listed" when used in RLS but there was absence of the other two criteria. Details regarding the development, use and clinimetric properties of each instrument are summarized along with the recommendations of the Task Force., Results and Conclusion: The Restless Legs Syndrome Quality of Life Scale-Abetz (RLS-QOL-Abetz) is the only scale designated as Recommended for use in cross-sectional assessments and treatment-related changes in RLS quality of life. Daily diaries hold future promise for the evaluation of RLS symptoms without the need for retrospective recall. An important need is the development of pediatric RLS quality of life instruments., (© 2014 American Academy of Sleep Medicine.)

Objectives: Over the last decade, increased research on therapy, pathogenesis, epidemiological and genetic aspects of restless legs syndrome/Willis-Ekbom Disease (RLS/WED) has necessitated development of diagnostic instruments specific to RLS. The Movement Disorder Society commissioned a task force to formally evaluate the available evidence on diagnostic instruments in RLS., Methods: A literature search identified 4 instruments specific to RLS. Each instrument was evaluated by 3 criteria, which included (a) use in RLS, (b) use by groups other than the group that developed the instrument, and (c) formal validation and adequate clinimetric properties. Instruments were then qualified as "Recommended" when all 3 criteria were met, "Suggested" when used for RLS but only one of the other criteria are met, and "Listed" when used in RLS but there is absence of the other 2 criteria. Details regarding the development, use, and clinimetric properties of each instrument are summarized, along with the recommendations of the committee., Results and Conclusion: The Recommended diagnostic instruments are the Hening Telephone Diagnostic Interview (HTDI), the Cambridge-Hopkins diagnostic questionnaire for RLS (CH-RLSq), and the RLS Diagnostic Index (RLS-DI). An unmet need is the development of a diagnostic instrument for pediatric RLS. Diagnostic instruments are particularly useful in studies where patients are not personally interviewed or examined in the office setting., (© 2014 American Academy of Sleep Medicine.)