REF-1660 · Winkelman et al., 2025 · Journal of Clinical Sleep Medicine, · Paper · PubMed

The AASM restless legs guideline starts with iron studies and aggravating factors: check ferritin and transferrin saturation in every patient with clinically significant restless legs (iron if ferritin ≤75 ng/mL or saturation <20%, IV iron only at 75-100 ng/mL, thresholds untested), address alcohol, caffeine, antihistaminergic, serotonergic and antidopaminergic drugs and untreated sleep apnoea, then use gabapentinoids or IV ferric carboxymaltose (strong, moderate certainty) rather than the standard use of dopamine agonists

Main caveat: Read from the abstract; the evidence tables, effect sizes and the systematic review behind the guideline were not read.
moderate evidenceMeasured on a mixed groupRead from the abstract only

An American Academy of Sleep Medicine task force wrote treatment recommendations for adults and children with restless legs syndrome (RLS) or periodic limb movement disorder (PLMD). It graded the literature from a systematic review with GRADE, weighed benefit against harm, what patients value and the resources involved, and the AASM Board approved the result.

Three good practice statements, based on expert consensus, come first. Every patient with clinically significant RLS should have serum iron studies, including ferritin and transferrin saturation, tested regularly, ideally in the morning and with no iron-containing supplements or foods for at least 24 hours before.

By untested consensus thresholds, adults get oral or IV iron if ferritin is ≤75 ng/mL or transferrin saturation <20%, and IV iron only if ferritin is 75-100 ng/mL; children get iron below 50 ng/mL; the authors note that these differ from general-population iron guidance.

The first step in management is to address aggravating factors: alcohol, caffeine, antihistaminergic, serotonergic and antidopaminergic medications, and untreated obstructive sleep apnoea. Pregnancy-specific safety should guide treatment choice.

Among the graded recommendations for adults, gabapentin enacarbil, gabapentin, pregabalin and IV ferric carboxymaltose are strongly recommended; the standard use of levodopa and the dopamine agonists pramipexole, rotigotine and ropinirole is advised against, conditionally, with long-term adverse effects, particularly augmentation, as the concern; cabergoline is strongly advised against.

Participants

Not a study: recommendations for adults and children with RLS or PLMD, with separate statements for adults with end-stage renal disease and for pregnancy.

Methods

Task force of sleep medicine experts commissioned by the AASM; recommendations and strengths based on a systematic review and GRADE assessment; the task force summarised the evidence and its certainty and weighed benefit against harm, patients' values and preferences, and cost in resources; approved by the AASM Board of Directors.
Good practice statements: expert consensus. Recommendations: "strong" (clinicians should follow under most circumstances) or "conditional", each with a certainty of evidence.
Number of studies and effect sizes: not in this abstract; the systematic review behind the guideline was not read.
Funding and interests: funded by the AASM; several authors report roles with RLS organisations and industry, listed in the PubMed record.

Key Results

Good practice statements (expert consensus):

Iron studies (ferritin, transferrin saturation) in all patients with clinically significant RLS, ideally in the morning, no iron-containing supplements or foods for at least 24 h before. Adults: oral or IV iron if ferritin ≤75 ng/mL or saturation <20%; IV only if ferritin 75-100 ng/mL. Children: iron if ferritin <50 ng/mL. Thresholds not empirically tested; different from general-population guidance.
First step: address alcohol, caffeine, antihistaminergic, serotonergic and antidopaminergic medications, and untreated obstructive sleep apnoea.
Pregnancy: consider each treatment's pregnancy-specific safety.

Graded recommendations, adults with RLS:

TreatmentDirectionStrengthCertainty
Gabapentin enacarbilforstrongmoderate
Gabapentinforstrongmoderate
Pregabalinforstrongmoderate
IV ferric carboxymaltose (appropriate iron status)forstrongmoderate
IV low molecular weight iron dextran (appropriate iron status)forconditionalvery low
IV ferumoxytol (appropriate iron status)forconditionalvery low
Ferrous sulfate (appropriate iron status)forconditionalmoderate
Dipyridamoleforconditionallow
Extended-release oxycodone and other opioidsforconditionalmoderate
Bilateral high-frequency peroneal nerve stimulationforconditionalmoderate
Levodopaagainst standard useconditionalvery low
Pramipexoleagainst standard useconditionalmoderate
Transdermal rotigotineagainst standard useconditionallow
Ropiniroleagainst standard useconditionalmoderate
Bupropionagainstconditionalmoderate
Carbamazepineagainstconditionallow
Clonazepamagainstconditionalvery low
Valerianagainstconditionalvery low
Valproic acidagainstconditionallow
Cabergolineagainststrongmoderate
Levodopa and the dopamine agonists may still be used by patients who value short-term symptom relief above long-term adverse effects, particularly augmentation.
Adults with RLS and end-stage renal disease: gabapentin (conditional, very low), IV iron sucrose when ferritin <200 ng/mL and saturation <20% (conditional, moderate) and vitamin C (conditional, low) suggested; standard use of levodopa (conditional, low) and rotigotine (conditional, very low) advised against.
Adults with PLMD: triazolam and valproic acid advised against (conditional, very low).
Children with RLS: ferrous sulfate with appropriate iron status (conditional, very low).

Practical Application

Restless legs that disturb sleep are a reason to see a doctor and have iron studies, not to self-treat. The guideline's first moves are morning ferritin and transferrin saturation, with no iron-containing supplements or food for 24 h before the draw, and dealing with what aggravates the condition.
The aggravators an athlete can bring to that appointment: alcohol, caffeine, antihistaminergic, serotonergic and antidopaminergic medications, and untreated obstructive sleep apnoea. Noting caffeine and alcohol timing and listing current medications helps the doctor; changing a medication is the prescriber's decision.
The RLS iron thresholds are not the athlete iron thresholds. Iron for RLS at ferritin up to 75 ng/mL (and IV iron at 75-100) is untested consensus for patients with RLS, and the authors say it differs from general guidance; it is no reason for an athlete to start iron without a blood test and a doctor (SYNTH-97).
A sleep physician decides diagnosis and treatment. Gabapentinoids, iron and the other options are prescribed by a sleep physician or the athlete's doctor; the assistant does not diagnose restless legs or suggest drugs. Valerian and clonazepam, sometimes taken for sleep, are among the treatments the guideline suggests against for RLS (very low certainty).
Not from this paper: whether exercise helps or worsens restless legs (no exercise recommendation in the abstract; how people with restless legs say exercise affects them is surveyed in REF-1662); magnesium (not in the abstract; REF-1596); how to tell RLS from cramps or sleep starts (REF-1661 gives the diagnostic criteria).

Limitations

Read from the abstract; the evidence tables, effect sizes and the systematic review behind the guideline were not read.
The good practice statements, the aggravating-factor list included, are expert consensus; the authors say the iron thresholds have not been empirically tested.
Patients with RLS or PLMD, not athletes; no exercise recommendation appears in the abstract.
Funded by the AASM; several authors hold roles with RLS organisations or have industry ties (PubMed record).
A US guideline; drug availability and licensing differ by country.
Written from the abstract and the PubMed record; full text not read.
How this entry was checked and changed
Why this level

a GRADE guideline built on a systematic review, but read from the abstract only, and a guideline or consensus statement reaches A only when read in full; the abstract does give each recommendation's strength and certainty (moderate to very low), while the good practice statements, iron thresholds included, are expert consensus the authors say has not been empirically tested

Content correction 2026-11-07
2026-11-07: added from the abstract and the PubMed record; level B+ (GRADE guideline read from the abstract only).