What Causes Restless Legs Syndrome and What Are the Treatment Options?

• 26 September 2018
• Dr. Obinna Nwobi

Restless legs syndrome (RLS) is a neurological sleep-related movement disorder — an urge to move the legs, usually with uncomfortable sensations, that gets worse in the evening and eases when you move. Its strongest known drivers are low iron in the brain and dopamine signalling problems, and it is often secondary to something else: iron deficiency, pregnancy, kidney disease, certain medications — and, in a vein-clinic population, superficial venous reflux. Treatment starts with removing triggers and correcting iron. Guideline-preferred medications changed in 2025: the alpha-2-delta ligands (gabapentin, gabapentin enacarbil, pregabalin) are now strongly recommended, while the older dopamine agonists are recommended against for routine use because of augmentation. If you also have visible varicose veins, aching, or leg swelling, a duplex ultrasound is worth doing before you commit to long-term RLS medication.

What restless legs syndrome actually feels like

Reuse the existing symptom list (it’s accurate) but frame it against the five IRLSSG essential criteria in plain language: (1) urge to move the legs, usually with uncomfortable sensations; (2) worse at rest; (3) relieved by movement; (4) worse in the evening or night; (5) not explained by another condition — the fifth criterion added in the 2014 update, and the reason a look-alike condition needs ruling out. Include: up to 7–10% of the U.S. population may have RLS; more common in women; more frequent and longer-lasting with age; untreated moderate-to-severe RLS is associated with roughly a 20% decrease in work productivity; more than 80% of people with RLS also have periodic limb movements of sleep (NINDS).

What causes restless legs syndrome? 

•  Brain iron and dopamine.

  Low brain iron is now regarded as an important underlying cause — which is why the 2025 guideline elevated iron testing for everyone with clinically significant RLS.

• Iron deficiency in the body.

  Diet, absorption, GI blood loss, heavy menstrual periods.

• Family history.

  RLS frequently runs in families.

• Other medical conditions.

  Kidney disease/end-stage renal disease, Parkinson’s disease, diabetes, rheumatoid arthritis. (Kidney disease has its own overlap with our practice — see internal link to the dialysis content.)

• Pregnancy.

  Common in pregnancy; usually improves after delivery. ⚠️ see C5

• Medications and substances that make RLS worse.

  Antihistamines, anti-nausea (antidopaminergic) drugs, antidepressants/serotonergic agents, antipsychotics; plus alcohol, caffeine, and untreated obstructive sleep apnea. The 2025 guideline is explicit that the first step in management is addressing these exacerbating factors — which means a medication review can be more valuable than a new prescription.

• Venous reflux: the cause most often missed

The vein connection: why a vascular surgeon should be part of an RLS work-up 

• The idea is not new — venous disease was proposed as a cause of restless legs by Karl-Axel Ekbom in 1944 and then went largely unexplored.
• In a modern vein-center series of 207 patients, RLS symptoms were significantly more common in people with superficial venous reflux (or combined superficial and deep reflux) than in those without reflux; on multivariable analysis, superficial reflux and a family history of venous reflux were independently associated with RLS symptoms. Of 99 RLS patients who underwent ablation, 93 had duplex-proven resolution of reflux and 81 (87%) reported RLS symptom improvement.
• A prospective series of 35 patients with moderate-to-very-severe RLS and duplex-proven superficial venous insufficiency treated with endovenous laser ablation plus foam sclerotherapy saw mean IRLS scores fall 26.9 → 5.5 (≈80% improvement); 31% reported complete relief.
• A separate retrospective review of 35 patients treated with radiofrequency ablation plus ultrasound-guided foam sclerotherapy saw IRLS 19.83 → 7.89 (≈63% improvement); 29% reached a score of zero.
• State the limitation plainly: these are small, mostly retrospective, vein-clinic populations without randomised controls, and the authors themselves call for randomised prospective trials using strict RLS criteria. Treating venous reflux is not a proven cure for RLS in the general population. What the evidence does support is this: if you have RLS symptoms, venous reflux deserves to be ruled out before you’re committed to years of medication — which is exactly what the ELA authors concluded.
• What that means practically: a painless duplex ultrasound of the legs. If reflux is found and you have venous symptoms, treating it may help both problems. If no reflux is found, you’ve cleared a look-alike cause and can pursue neurological care with a cleaner picture.

 How restless legs syndrome is treated in 2026

Step 1: remove what’s making it worse.

(per above)

• Step 2: check and correct iron.

  Ferritin + transferrin saturation, morning draw. Oral or IV iron per thresholds; IV ferric carboxymaltose is a strong recommendation in adults with appropriate iron status. ⚠️ C2

• Step 3: rule out venous reflux

  (duplex ultrasound — what we do).

• Step 4: medication, and what changed.

  Alpha-2-delta ligands (gabapentin enacarbil — the only remaining FDA-approved medication for RLS carried in the guideline — plus gabapentin and pregabalin) are strong recommendations and are not associated with augmentation. Possible side effects include sedation and unsteadiness. The dopamine agonists that were the 20-year gold standard are now conditionally recommended against for routine use.

• What is augmentation, and why it changed the guidelines.

  Plain-language: symptoms creeping earlier in the day, spreading to other body parts, and becoming more severe overall — caused by the medication itself, appearing after months to years, which is why the original short drug trials missed it. This paragraph is the single most useful thing on the page for a patient already on pramipexole or ropinirole, and it is why the page should end with “talk to your prescriber, don’t stop on your own.”

• Non-drug options.

  Movement, stretching, sleep timing, leg elevation if venous symptoms coexist; peroneal nerve stimulation has a conditional recommendation. ⚠️ Dr. Nwobi: confirm what we say about at-home measures.

When to see a doctor about restless legs

Sleep is being disrupted ≥2 nights/week · daytime function affected · symptoms creeping earlier in the day on current medication (possible augmentation) · you also have varicose veins, aching, heaviness, ankle swelling, skin discoloration, or a healed/open ankle sore.

Frequently asked questions 

Vein evaluation for restless legs in Central Florida

FAQs

Q: What is the main cause of restless legs syndrome? A: There isn’t a single cause. The best-supported mechanism involves low iron in the brain and disrupted dopamine signalling. In many people RLS is secondary to something identifiable — iron deficiency, pregnancy, kidney disease, a medication such as an antihistamine or antidepressant, or (in vein-clinic populations) superficial venous reflux. A work-up is about finding your driver.

Q: Can varicose veins cause restless legs? A: Varicose veins and RLS symptoms occur together more often than chance would predict, and in published vein-clinic series most patients whose reflux was successfully treated reported their RLS symptoms improved. These studies are small and not randomised, so this is best described as an association worth investigating rather than a proven cause. If you have both, a duplex ultrasound is a reasonable next step.

Q: Does treating veins cure restless legs? A: No — not as a general claim. In selected patients with duplex-proven superficial venous reflux, treating the reflux has been reported to reduce RLS severity substantially, and a minority reported complete relief. It is not a cure for RLS in people without venous reflux.

Q: Are dopamine medications still used for restless legs? A: They’re used far more cautiously now. The 2025 American Academy of Sleep Medicine guideline suggests against the routine use of levodopa, pramipexole, ropinirole and transdermal rotigotine because of augmentation — a medication-caused worsening of RLS over months to years — and recommends against cabergoline. Alpha-2-delta ligands such as gabapentin enacarbil, gabapentin and pregabalin are now strongly recommended. Never stop or change a prescription on your own; talk to the prescriber.

Q: Should I take iron for restless legs? A: Only with testing. Iron helps when iron stores are low, and the thresholds used in RLS are different from general-population ones — which is why the guideline advises checking ferritin and transferrin saturation (a morning blood draw, no iron-containing supplements or foods for 24 hours beforehand) before supplementing.

Q: Is restless legs syndrome a sign of a blood clot or poor circulation? A: RLS itself is a neurological movement disorder, not a clot. But new one-sided leg swelling, calf pain or tenderness, warmth or redness can indicate deep vein thrombosis and needs urgent assessment — that is a different problem from RLS. Persistent leg pain at rest or a non-healing foot or ankle wound also needs prompt vascular evaluation.

Q: How common is restless legs syndrome? A: NINDS estimates up to 7–10% of the U.S. population may have RLS, more often women, and symptoms tend to become more frequent and longer-lasting with age. Most cases can be managed.

7. Emergency / safety box 

Get urgent care, don’t wait for an appointment, if you have:

• New swelling, pain, tenderness, warmth or redness in one leg — possible deep vein thrombosis
• Sudden shortness of breath, chest pain, coughing up blood, or fainting — possible pulmonary embolism: call 911
• Leg or foot pain at rest, a cold or pale foot, or a wound that won’t heal — possible critical arterial disease

These are not restless legs syndrome. RLS eases when you move; these do not. Do not stop or change a prescribed RLS medication on your own. If symptoms are appearing earlier in the day or spreading, contact your prescriber — that pattern may be augmentation.

Restless legs and leg veins — one visit can rule out the vein cause

If your restless legs come with visible varicose veins, aching, heaviness, or ankle swelling, a duplex ultrasound can show whether venous reflux is contributing before you commit to long-term medication. Dr. Obinna Nwobi is a board-certified vascular surgeon; Vein Health Clinics sees patients at five Central Florida locations.

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Citations

1. AASM clinical practice guideline, Treatment of restless legs syndrome and periodic limb movement disorder, J Clin Sleep Med, Jan 1 2025 — doi:10.5664/jcsm.11390 (PMID 39324694). Strong recommendations: gabapentin enacarbil, gabapentin, pregabalin, IV ferric carboxymaltose. Conditional against: levodopa, pramipexole, ropinirole, transdermal rotigotine. Strong against: cabergoline. Good-practice statement on iron testing and thresholds (ferritin ≤75 ng/mL or TSAT <20%; IV only 75–100 ng/mL) and on addressing exacerbating factors first.
2. AASM guideline summary, aasm.org/summary-of-new-clinical-practice-guideline-for-rls-and-plmd/ — plain-language account of the augmentation-driven downgrade of dopaminergics.
3. NINDS, Restless Legs Syndrome fact sheet (ninds.nih.gov, 2025 revision) — up to 7–10% of the U.S. population; more common in women; ~20% decrease in work productivity in untreated moderate-to-severe RLS; >80% also have PLMS.
4. IRLSSG 2014 consensus diagnostic criteria — Allen RP et al., Sleep Med 2014; doi:10.1016/j.sleep.2014.03.025 (PMID 25023924). Fifth essential criterion = differential diagnosis; ~2–3% of adults have clinically significant RLS in European/American populations.
5. Correlation Between Restless Leg Syndrome and Superficial Venous Reflux — PMID 34853576. 207 patients; SVR and family history independently associated with RLS symptoms; 81/93 (87%) reported improvement after ablation with duplex-proven reflux resolution.
6. The effect of endovenous laser ablation on restless legs syndrome — Hayes CA et al., Phlebology 2008;23(3):112–117; doi:10.1258/phleb.2007.007051. 35 patients; IRLS 26.9 → 5.5 (≈80%); 31% complete relief. Also the source for Ekbom’s 1944 proposal and for “rule out SVI before starting or continuing drug therapy.”
7. Treatment of Leg Veins for Restless Leg Syndrome: A Retrospective Review — Cureus 2019; doi:10.7759/cureus.4368. 35 patients, RFA + UGFS; IRLS 19.83 → 7.89 (≈63%); 29% score of 0; RLS observed in 31.3% of those with duplex-proven SVR.
8. IRLSSG/EURLSSG/RLS-F augmentation task force — Sleep Med 2016; doi:10.1016/j.sleep.2016.01.017. α2δ ligands as initial therapy to prevent augmentation.