Evidence catalog
Restless legs syndrome research: every study behind this project
One graded entry per study: its citation, evidence grade, study type, language, and the topics it speaks to. Search, filter, and open any entry for its full summary.
This is a searchable database of 651 independently verified, evidence-graded studies behind every claim on this site, filterable by topic, evidence grade, study type, language, and year.
651
Verified studies
652
Notes checked
2026-09-12
Last verification pass
Only citations that passed a manual verification pass against PubMed/DOI records are shown here (651 of 652 notes checked, 1 unverifiable, excluded). See Sources for the full verification methodology and disclaimer.
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- Alpha-2-Delta Ligands in RLS44
Alpha-2-delta ligands relieve RLS symptoms about as well as dopamine agonists, without dopaminergic augmentation. A network meta-analysis of 35 RCTs (7333 patients) found…
- Behavioural, psychological, and self-management approaches to RLS20
Synthesis of the evidence on the behavioural and psychological backbone of a non-drug, long-term RLS plan: CBT-I and CBT adapted for RLS, relaxation and mind-body practice, the…
- Brain iron deficiency in RLS54
Brain iron deficiency (BID) is one of the two core pathophysiological pillars of RLS named in this project's anchor facts (Master Plan Section 3), alongside altered dopamine…
- Circadian chronobiology and melatonin in RLS32
Synthesis of the evidence that Restless Legs Syndrome (RLS) has an intrinsic circadian (clock-driven), not merely rest-dependent, pattern of symptom expression; the phase…
- Clinical Trials Pipeline and Pharmacology Data18
Alpha2delta ligands and gabapentin enacarbil are the best-supported non-dopaminergic drug class, with equivalent efficacy to rotigotine and pregabalin shown in a comparative…
- Devices and neuromodulation34
Synthesis of the evidence on non-drug device and neuromodulation therapies for RLS: peripheral tonic motor activation/nerve stimulation (TOMAC/Nidra), pneumatic compression,…
- Dopamine agonists and augmentation86
Synthesis of the evidence on dopamine agonist (pramipexole, ropinirole, rotigotine), levodopa, and alpha-2-delta ligand (pregabalin, gabapentin, gabapentin enacarbil) treatment…
- The Dopamine System in RLS35
This synthesis covers the A11 diencephalospinal pathway, striatal/spinal D1-D3 receptor biology, presynaptic "hyperdopaminergic" signaling, tyrosine hydroxylase and DAT changes,…
- Genetics and Epidemiology of RLS84
RLS is substantially genetic, with MEIS1 as the dominant common-variant risk factor. The founding 2007 genome-wide association studies independently identified MEIS1, BTBD9, and…
- Glutamate, Adenosine and Hyperarousal in RLS33
This topic covers the non-dopaminergic "second pillar" of RLS pathophysiology: thalamic/cortical glutamatergic hyperactivity, adenosine A1-receptor hypofunction, endogenous opioid…
- Clinical guidelines worldwide (comparison)10
Synthesis comparing national and international RLS clinical practice guidelines (diagnosis and treatment algorithms) across the US, Europe (international and national), Germany,…
- Gut, microbiome and inflammation in RLS41
This synthesis covers small intestinal bacterial overgrowth (SIBO), irritable bowel syndrome (IBS), celiac disease, inflammatory bowel disease (Crohn's disease and ulcerative…
- Iron therapy (oral and IV)89
Synthesis of the evidence on oral and intravenous iron treatment for RLS/Willis-Ekbom disease: efficacy, dosing, formulation differences, safety (notably hypophosphatemia), and…
- Lifestyle, exercise, diet, and supplements45
Synthesis of the evidence on non-drug lifestyle interventions for RLS: aerobic/resistance exercise, yoga and relaxation-based mind-body practice, cognitive behavioural approaches,…
- Long-term outcomes and harms: natural history, deprescribing durability, and combination safety18
Synthesis of what is actually known about (1) the multi-year natural course of RLS, with and without treatment, and (2) the long-term harms of the drugs patients on a…
- Molecular Mechanisms: Hypoxia-HIF-Adenosine-Iron Axis and RLS Gene Function45
This synthesis targets the two mechanism families flagged as thin for the mechanistic brain simulation (deliverable R2-A): (a) the hypoxia/HIF-adenosine-iron axis linking…
- Opioids, other drugs, and drugs that worsen RLS28
Synthesis of the evidence on (a) opioids (oxycodone-naloxone, methadone, buprenorphine, tramadol) as a treatment/bridge option for treatment-refractory or…
- Outcome measures, placebo/nocebo magnitude, and objective sleep measurement in RLS20
Synthesis of how RLS severity, augmentation, and quality of life are actually measured, how large the placebo and nocebo response is in RLS trials, and what objective…
- Secondary RLS and comorbidities73
Synthesis of the evidence on RLS/Willis-Ekbom disease arising alongside, or apparently secondary to, other medical conditions: chronic kidney disease/dialysis/transplant,…
- Sex hormones, pregnancy, and the life course of RLS23
RLS is roughly twice as common in women as in men, and pregnancy is the single largest natural experiment in reversible RLS: onset or worsening in pregnancy, frequent (though not…
- Spinal, Peripheral and PLMS Mechanisms in Restless Legs Syndrome53
This synthesis covers the evidence on spinal cord hyperexcitability, peripheral (nerve, vascular, autonomic) contributions, and the physiology/consequences of periodic limb…
- Getting off dopamine agonists: tapering and deprescribing35
Synthesis of the evidence on de-escalating chronic dopamine agonist (pramipexole, ropinirole, rotigotine) therapy for RLS - and, more broadly, on reducing reliance on any…