Altered mental status in older adults with histamine2-receptor antagonists: a population-based study

Eur J Intern Med. 2014 Oct;25(8):701-9. doi: 10.1016/j.ejim.2014.06.021. Epub 2014 Jul 16.


Background: Standard doses of histamine2-receptor antagonists (H2RAs) may induce altered mental status in older adults, especially in those with chronic kidney disease (CKD).

Methods: Population-based cohort study of older adults who started a new H2RA between 2002 and 2011 was conducted. Ninety percent received the current standard H2RA dose in routine care. There was no significant difference in 27 baseline patient characteristics. The primary outcome was hospitalization with an urgent head computed tomography (CT) scan (proxy for altered mental status), and the secondary outcome was all-cause mortality also within 30days of a new H2RA prescription.

Results: Standard vs. low H2RA dose was associated with a higher risk of hospitalization with an urgent head CT scan (0.98% vs. 0.74%, absolute risk difference 0.24% [95% CI 0.11% to 0.36%], relative risk 1.33 [95% CI 1.12 to 1.58]). This risk was not modified by the presence of CKD (interaction P value=0.71). Standard vs. low H2RA dose was associated with a higher risk of mortality (1.07% vs.0.74%; absolute risk difference 0.34% [95% CI 0.20% to 0.46%], relative risk 1.46 [95% CI 1.23 to 1.73]).

Interpretation: Compared to a lower dose, initiation of the current standard dose of H2RA in older adults is associated with a small absolute increase in the 30-day risk of altered mental status (using neuroimaging as a proxy), even in the absence of CKD. This risk may be avoided by initiating older adults on low doses of H2RAs for gastroesophogeal reflux disease, and increasing dosing as necessary for symptom control.

Keywords: Aged; Altered mental status; Chronic renal insufficiency; Cohort studies; Histamine H2 antagonists; Risk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cognition Disorders / chemically induced*
  • Delirium / chemically induced*
  • Delirium / epidemiology
  • Dose-Response Relationship, Drug
  • Female
  • Glomerular Filtration Rate
  • Head / diagnostic imaging
  • Histamine H2 Antagonists / administration & dosage
  • Histamine H2 Antagonists / adverse effects*
  • Hospitalization / statistics & numerical data*
  • Humans
  • Male
  • Renal Insufficiency, Chronic / epidemiology
  • Risk Assessment
  • Tomography, X-Ray Computed


  • Histamine H2 Antagonists