Association of proton pump inhibitor and histamine H2-receptor antagonists with restless legs syndrome

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  • Eric J. Earley, Research Triangle Institute International
  • ,
  • Maria Didriksen, Rigshospitalet
  • ,
  • Bryan R. Spencer, Yale University, American Red Cross Scientific Affairs, Boston
  • ,
  • Joseph E. Kiss, University of Pittsburgh, Vitalant Northeast Division, Pittsburgh
  • ,
  • Christian Erikstrup
  • Ole B. Pedersen, Næstved Hospital
  • ,
  • Erik Sørensen, Rigshospitalet, Danmark
  • Kristoffer S. Burgdorf, Rigshospitalet
  • ,
  • Steven H. Kleinman, University of British Columbia
  • ,
  • Alan E. Mast, Medical College of Wisconsin, Blood Systems Research Institute
  • ,
  • Michael P. Busch, University of California at San Francisco, Vitalant Research Institute
  • ,
  • Henrik Ullum, Rigshospitalet
  • ,
  • Grier P. Page, Research Triangle Institute International

Restless legs syndrome (RLS) is a common sensorimotor disorder, which can disrupt sleep and is thought to be caused in part by low cellular iron stores. Proton pump inhibitors (PPI) and histamine H2-receptor antagonists (H2A) are among the most commonly used drugs worldwide and show evidence of causing iron deficiency. We conducted a case/non-case observational study of blood donors in the United States (N = 13,403; REDS-III) and Denmark (N = 50,323; Danish Blood Donor Study, DBDS), both of which had complete blood count measures and a completed RLS assessment via the Cambridge-Hopkins RLS questionnaire. After adjusting for age, sex, race, BMI, blood donation frequency, smoking, hormone use, and iron supplement use, PPI/H2A use was associated with RLS (odds ratio [OR] = 1.41; 95% confidence interval [CI], 1.13-1.76; p = 0.002) in REDS-III for both PPI (OR = 1.43; CI, 1.03-1.95; p = 0.03) and H2A (OR = 1.56; CI, 1.10-2.16; p = 0.01). DBDS exhibited a similar association with PPIs/H2As (OR = 1.29; CI, 1.20-1.40; p < 0.001), and for PPIs alone (OR = 1.27; CI, 1.17-1.38; p < 0.001), but not H2As alone (OR = 1.18; CI, 0.92-1.53; p = 0.2). We found no evidence of blood iron stores mediating this association. The association of PPI, and possibly H2A, consumption with RLS independent of blood iron status and other factors which contribute to RLS risk suggest the need to re-evaluate use of PPI/H2A in populations at particular risk for RLS.

Antal sider7
StatusUdgivet - apr. 2021

Bibliografisk note

Publisher Copyright:
© Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep Research Society.

This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine

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