title: Cognitive and other adverse effects of diphenhydramine use in hospitalized older patients.
abstract: BACKGROUND
  Diphenhydramine hydrochloride is a commonly prescribed medicine in hospitalized patients, but its adverse effects on older patients remain unclear.
  
  
  METHODS
  We enrolled 426 hospitalized medical patients aged 70 years or older in a prospective cohort study in a university hospital. Measurements included baseline and daily assessments including Mini-Mental State Examination scores, Confusion Assessment Method ratings, direct observations for medical devices (urinary catheter or physical restraints), and blinded medical record extractions for diphenhydramine use.
  
  
  RESULTS
  Of the 426 patients, 114 (27%) received diphenhydramine during hospitalization and shared similar baseline characteristics including age, sex, delirium risk, and Mini-Mental State Examination scores compared with nonexposed patients. The diphenhydramine-exposed group was at an increased risk for any delirium symptoms (relative risk [RR], 1.7; 95% confidence interval [CI], 1.3-2.3) and for individual delirium symptoms, including inattention (RR, 3.0; 95% CI, 1.5-5.9), disorganized speech (RR, 5.5; 95% CI, 1.0-29.8), and altered consciousness (RR, 3.1; 95% CI, 1.6-6.1). Exposed patients also had increased risk for urinary catheter placement (RR, 2.5; 95% CI, 1.0-6.0) and longer median length of stay (7 vs 6 days; P =.009). A dose-response relationship was demonstrated for most adverse outcomes. Overall, 24% of diphenhydramine doses were administered inappropriately.
  
  
  CONCLUSIONS
  Diphenhydramine administration in older hospitalized patients is associated with an increased risk of cognitive decline and other adverse effects with a dose-response relationship. Careful review of its use is necessary in this vulnerable population.
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06504, USA.
authors.forename: J V
authors.initials: JV
authors.lastname: Agostini
authors.forename: L S
authors.initials: LS
authors.lastname: Leo-Summers
authors.forename: S K
authors.initials: SK
authors.lastname: Inouye
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003237:Connecticut; D003693:Delirium / Q000139:chemically induced* / Q000175:diagnosis; D004155:Diphenhydramine / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D015577:Geriatric Assessment; D006760:Hospitalization; D006785:Hospitals, University; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D011446:Prospective Studies; D012306:Risk
chemical_list: D004155:Diphenhydramine