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Sleep BODY HANDBOOK
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Restless Legs Syndrome (RLS)
You can't lie still. On the couch, in bed, on a long drive, your legs need to move: a deep crawling itch that eases the second you stand and comes back the second you sit. Doctors treat it as a leg problem and reach for a dopamine drug. It's a brain-iron problem, and for most people the fix is iron. The catch: the ferritin number your GP calls "normal" is the wrong threshold here, so the one test that would find it gets waved off.
Condition Evidence Moderate Chapter Sleep

The leg checks out on exam; the fault is upstream. Iron is the cofactor the brain uses to make dopamine, and people with RLS have measurably less of it where that pathway runs 1. Dopamine then drifts low in the evening, exactly when symptoms peak 2.

The diagnosis is a pattern, not a blood test. Five things at once: an urge to move the legs, at rest, relieved by movement, worse in the evening, and unexplained by a cramp or habit 3.

Then one lab changes everything: serum ferritin, your stored iron. Labs flag it low only under about 15–30 ng/mL, the anaemia floor; for RLS the cutoff to start oral iron is <75 ng/mL 4. A ferritin in the 30s or 50s that got called fine is only fine by the anaemia standard.

And the dopamine drugs are out as first-line. Pramipexole and ropinirole worsen the disease over years, so the 2025 guideline points to iron first 5.

Confirm the five-point pattern, get the labs, pull the aggravators, then start iron.

If repleted iron doesn't settle the legs, an alpha-2-delta drug like gabapentin enacarbil is next 6.

For most cases, which are iron-deficient, the evening becomes an evening again. Within weeks of an IV infusion, or two to four months of steady oral iron, the couch is sit-able and falling asleep takes minutes 6. One IV course buys some people years; others re-treat as ferritin drifts down 4.

RLS hits about one in five women by the third trimester, often new; oral iron is the mainstay there and it usually resolves postpartum 7. Prevalence is double in women overall and often waved off as anxiety, so push for the test 8.

The fine print β€” when to skip it, and what people get wrong

Why "iron didn't work": ferritin moves over months, so a two-week trial isn't one 4. Symptoms creeping earlier and into the arms on long-term pramipexole is augmentation, needing a drug switch 9.

Don't start iron with haemochromatosis or another iron-overload condition; a high ferritin or transferrin saturation on the screen is a stop, and IV iron belongs in a clinical setting 45.

References
  1. 1Connor JR, Boyer PJ, Menzies SL et al. (2003). Neuropathological examination suggests impaired brain iron acquisition in restless legs syndrome. Neurology. link
  2. 2Trenkwalder C, Allen R, HΓΆgl B et al. (2018). Comorbidities, treatment, and pathophysiology in restless legs syndrome. Lancet Neurology. link
  3. 3Allen RP, Picchietti DL, Garcia-Borreguero D et al. (2014). Restless legs syndrome/Willis-Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria β€” history, rationale, description, and significance. Sleep Medicine. link
  4. 4Allen RP, Picchietti DL, Auerbach M et al. (2018). Evidence-based and consensus clinical practice guidelines for the iron treatment of restless legs syndrome/Willis-Ekbom disease in adults and children: an IRLSSG task force report. Sleep Medicine. link
  5. 5Winkelman JW, Berkowski JA, DelRosso LM et al. (2025). Treatment of restless legs syndrome and periodic limb movement disorder: an American Academy of Sleep Medicine clinical practice guideline. Journal of Clinical Sleep Medicine. link
  6. 6Allen RP, Adler CH, Du W et al. (2011). Clinical efficacy and safety of IV ferric carboxymaltose (FCM) treatment of RLS: a multi-centred, placebo-controlled preliminary clinical trial. Sleep Medicine. link
  7. 7Picchietti DL, Hensley JG, Bainbridge JL et al. (2015). Consensus clinical practice guidelines for the diagnosis and treatment of restless legs syndrome/Willis-Ekbom disease during pregnancy and lactation. Sleep Medicine Reviews. link
  8. 8Ohayon MM, O'Hara R, Vitiello MV (2012). Epidemiology of restless legs syndrome: a synthesis of the literature. Sleep Medicine Reviews. link
  9. 9Garcia-Borreguero D, Silber MH, Winkelman JW et al. (2016). Guidelines for the first-line treatment of restless legs syndrome/Willis-Ekbom disease, prevention and treatment of dopaminergic augmentation: a combined task force of the IRLSSG, EURLSSG, and the RLS-foundation. Sleep Medicine. link
Related in the handbook (5)
Helped by
  • β€” The first-line treatment for most cases isn't a drug β€” it's iron, often dramatically effective when ferritin is low.
  • β€” Magnesium is a cheap first thing to try for restless legs, especially if you're running low to begin with.
Detected by
  • β€” The single most useful test here is serum ferritin β€” but the routine 'normal' threshold is the wrong one for restless legs.
Related
  • β€” Restless legs is a classic symptom of iron being low in the brain even when blood counts look fine.
  • β€” Restless legs is a perfect example: the lab calls your ferritin normal, but for this you need it much higher.
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