Antibiotic Therapy May Improve Restless Legs Syndrome: A Randomized, Double-Blind, Placebo-Controlled Study of a Short Course of Rifaximin

LB Weinstock, MD1,2; S Zeiss, RN2; N Lewis, PA-C2; S Duntley, MD1; A Walters, MD3

1Washington University School of Medicine, St Louis, MO; 2Specialists in Gastroenterology, LLC, St Louis, MO; 3Vanderbilt University School of Medicine, Nashville, TN


An association between restless legs syndrome (RLS) and small intestinal bacterial overgrowth (SIBO) has recently been recognized.


We evaluated the efficacy of rifaximin, a nonsystemic antibiotic, for RLS treatment.


Patients with idiopathic RLS (international RLS [IRLS] score =15 and ferritin level =20 ng/mL) and healthy controls were screened for SIBO using a lactulose breath test (LBT). Patients with RLS and an abnormal LBT result received rifaximin 1650 mg/d or placebo for 10 days. IRLS scores were assessed at baseline and on days 11, 18, and 25.


Thirty of 39 patients (77%) and 7 of 27 controls (26%) had an abnormal LBT result. Patients who received rifaximin (n=20; 11F/9M; mean age, 53.2 ± 10.5 y) had a baseline IRLS score of 25.4 ± 4.8 and RLS for a mean of 12.0 ± 11.4 years. Within the rifaximin group, 10 patients (50%) had irritable bowel syndrome (IBS) and 16 (80%) had gastrointestinal (GI) symptoms. One patient in the placebo group (n=10) was excluded because of benzodiazepine use. The remaining patients who received placebo (n=9; 7F/2M; mean age, 60.9 ± 14.4 y) had a baseline IRLS score of 22.7 ± 5.3 and RLS for 10.9 ± 14.3 years. In the placebo group, 1 patient was diagnosed with IBS and 2 had GI symptoms. A similar percentage of patients in the rifaximin (30%) and placebo groups (33%) had low ferritin levels (20-50 ng/mL) at baseline. Eighteen days after initiation of rifaximin therapy, the mean change in IRLS score was -4.5 ± 6.6 in the rifaximin group (n=20) vs -0.6 ± 8.0 in the placebo group (n=9; P=0.444). The percentage of IRLS responders (ie, patients with a =6-point decrease from baseline in IRLS score) on day 18 was greater in the rifaximin group (50%) than in the placebo group (11%; P=0.096).

A total of 4 patients in the rifaximin group and 2 in the placebo group experienced marked or moderate worsening of global RLS symptoms during treatment. Two of these 4 rifaximin patients had lower IRLS scores on days 11 and 18 than at baseline, but their IRLS scores exceeded baseline scores on day 25.


GI symptoms and a positive LBT result suggesting SIBO are common in patients with idiopathic RLS. A short course of rifaximin 1650 mg/d showed a positive trend to decrease RLS severity. Further studies are warranted to determine the best dosing regimen of rifaximin in patients with RLS.


3rd International Congress on Sleep Medicine of the World Association of Sleep Medicine (Sao Paulo, Brazil)

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Restless legs syndrome, small intestinal bacterial overgrowth, antibiotic, rifaximin, lactulose breath test, international RLS scale


Movement Disorders

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Conflict of Interest statement:

Dr Weinstock is on the Speakers Bureau for Salix Pharmaceuticals.

Financial disclosure:

Dr. Weinstock is on the Salix Pharmaceuticals Speaker’s Bureau; Editorial assistance was provided under the direction of the authors by MedThink Communications with support from Salix Pharmaceuticals, Inc. Dr. Walters has received research funding from the National Institutes of Health; Xenoport Inc; Schwarz Pharma; and Kyowa Pharmaceuticals, Inc. Dr. Walters has received research funding from and is on the speaker’s bureau of GlaxoSmithKline and Boehringer-Ingelheim.