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Patient handout

Restless Legs Syndrome / Willis–Ekbom Disease

PRODUCTION

1. Your condition

This handout is for restless legs syndrome / willis–ekbom disease. Your care team identified this based on: urge to move the legs, usually with/caused by an uncomfortable or unpleasant leg sensation (irlssg essential criterion 1; aasm 2025 pmid 39324694).

Other reasons your team may use this plan: symptoms begin or worsen during rest or inactivity (sitting, lying — criterion 2); partial or total relief by movement (walking, stretching) at least as long as the activity continues (criterion 3); worse in the evening/night than during the day, or only occurs in evening/night (criterion 4).

2. Your medications

Take these medications exactly as prescribed. Do not stop or change a dose without talking to your provider.

MedicationStarting doseHowWhenWhat it does
ferrous sulfate325 mg (≈65 mg elemental iron) + vitamin C 100-200 mg, alternate-day single dose (maximises fractional absorption — cross-ref heme.iron-deficiency-anemia.core.v1)POevery other dayIRLSSG iron consensus PMID 29425576 — oral iron when ferritin ≤75 ng/mL & TSAT >20%; AAN 2016 Level B (ferrous sulfate + vitamin C) PMID 27856776; alternate-day dosing blunts hepcidin (cross-ref heme.iron-deficiency-anemia.core.v1)
ferric carboxymaltose750-1000 mg IV (per weight/regimen); recheck ferritin/TSAT before re-dosingIVsingle/two-dose courseFCM RCT IRLS decrease 8.9 vs 4.0, CGI-I much/very-much improved 48.3% vs 14.3% (corroborated PMID 28643901); IRLSSG iron consensus PMID 29425576 — IV iron when oral inappropriate / ferritin ≤100; strong evidence; preferred in CKD
iron sucrose200 mg IV per session, multiple sessions to target doseIVmultiple sessionsAlternative IV iron — IRLSSG iron consensus PMID 29425576; often the dialysis-unit formulary IV iron
IV iron infusion procedure + premedication/monitoringInfusion-reaction monitoring; hypophosphataemia surveillance with repeated FCM (cross-ref heme.iron-deficiency-anemia.core.v1)
sleep hygiene + moderate exercise + avoid evening caffeine/alcohol/nicotineFoundational non-pharmacologic measures (AASM 2025 PMID 39324694; Silber 2021 PMID 34218864)
withdraw RLS-aggravating drugsAntihistamines, dopamine antagonists/antiemetics, mirtazapine/SSRI/SNRI, antipsychotics, alcohol/caffeine/nicotine worsen RLS; switch antidepressant to bupropion (RxCUI 42347; RLS-neutral/beneficial)
pneumatic compression deviceAAN 2016 Level B (PMID 27856776) — consider when a non-pharmacologic approach is desired; NIRS / rTMS Level C

Plan: RLS/WED chronic management — iron repletion → alpha-2-delta first-line → dopamine agonist limited → low-dose opioid refractory (AASM 2025 PMID 39324694; IRLSSG iron PMID 29425576; Garcia-Borreguero 2016 PMID 27448465)

3. When to call your provider

Contact your care team if any of the following happen:

  • Refractory despite iron repletion + adequate alpha-2-delta → sleep-medicine/neurology referral
  • Augmentation on any dopaminergic agent → specialist
  • Impulse-control disorder on dopamine agonist → discontinue + specialist
  • Severe pregnancy RLS → OB co-management + specialist
  • CKD/ESRD secondary RLS → nephrology (neph.ckd.core.v1)

4. When to seek emergency care

Call 911 or go to the nearest emergency room right away if you have:

  • Augmentation on dopaminergic therapy — RLS symptoms now occurring EARLIER in the day, MORE intense, SPREADING to other body parts, or shorter rest-latency, especially after a dose increase; the central long-term hazard of dopaminergic RLS therapy (Garcia-Borreguero 2016 PMID 27448465)
  • Impulse-control disorder on a dopamine agonist — pathological gambling, compulsive shopping, hypersexuality, binge-eating, or punding (~17% any ICD on dopaminergic RLS therapy; Cornelius 2010 PMID 20120624)
  • Severe refractory RLS with major sleep deprivation and quality-of-life collapse despite iron repletion + adequate alpha-2-delta (± dopamine-agonist rotation) — specialist + low-dose opioid pathway
  • Augmentation-deprescribing trigger (quantified): on long-term short-acting dopaminergic therapy, augmentation accrues at ~5-8%/yr cumulatively (up to ~40-70% over years on levodopa/short-acting dopamine agonists; Garcia-Borreguero 2016 PMID 27448465) — once augmentation criteria are met, DEPRESCRIBE the dopaminergic (do NOT up-titrate). Switching pramipexole 0.5 mg → pregabalin reduced 40-52-wk augmentation from 7.7% to 2.1% (Allen NEJM 2014 PMID 24521108). Action: ensure ferritin/TSAT repleted (ferritin ≤75 / TSAT <20% per IRLSSG iron consensus PMID 29425576), cross-taper OFF the dopamine agonist over 1-2 wk, bridge to an alpha-2-delta ligand and/or low-dose prolonged-release oxycodone-naloxone (Trenkwalder 2013 PMID 24140442 — IRLS 31.7→15.1 vs placebo 31.6→22.1 at wk 12, n=304).

5. Follow-up

Iron recheck 8-12 wk after repletion (and before re-dosing IV iron); titrate alpha-2-delta to effect; pregnancy RLS usually remits postpartum (de-prescribe); periodic aggravator review; long-term opioid stewardship; re-evaluate diagnosis if refractory despite repletion + adequate first-line therapy

6. Sources

Guideline: 2025 AASM Clinical Practice Guideline — Treatment of RLS and PLMD (Winkelman, JCSM 2025; NEWEST — primary floor) + AASM 2025 systematic review/meta-analysis/GRADE + AAN 2016 practice guideline + IRLSSG iron-treatment consensus (Allen 2018) + IRLSSG/EURLSSG/RLS-F first-line + augmentation guideline (Garcia-Borreguero 2016) + Silber Mayo updated algorithm 2021

  1. pubmed.ncbi.nlm.nih.gov/39324694
  2. pubmed.ncbi.nlm.nih.gov/39324664
  3. pubmed.ncbi.nlm.nih.gov/27856776