ORIGINAL ARTICLES
Increased risk of serious injury following an initial prescription for diphenhydramine

https://doi.org/10.1016/S1081-1206(10)61950-3Get rights and content

Background

Diphenhydramine may be associated with excess risk of injury relative to nonsedating H1-receptor antagonists.

Objective

This study sought to compare the risk of injury in patients exposed to diphenhydramine with the risk of injury in patients exposed to loratadine.

Methods

A retrospective cohort study of injury was carried out in 12,106 patients whose initial antihistamine prescription was for diphenhydramine and in 24,968 patients whose initial antihistamine prescription was for loratadine. Data were taken from a health care claims database that included employees, dependents, and retirees who filed claims from January 1991 through December 1998. Rates of six serious injuries in the diphenhydramine cohort after and before the first prescription were compared with rates in the loratadine cohort after and before the first prescription.

Results

In the 30 days after the first antihistamine prescription, the rate of all injuries was 308 per 1,000 person-years in the diphenhydramine cohort versus 137 per 1,000 person-years in the loratadine cohort. The rate ratio estimate adjusted for age and gender using Poisson regression was 2.27 (95% confidence limits [CL] 1.93, 2.66). In the corresponding 30 days of the preceding year, the injury rates in the diphenhydramine and loratadine cohorts were 128 and 125 per 1,000 person-years, and the adjusted rate ratio was 1.02 (CL 0.83, 1.26). Thus, the cohorts appeared to have similar preprescription injury rates. The differences between the cohorts declined with time from prescription: For all injuries, the estimated percentage decline in the rate ratio was 4.1% per day (CL 3.3, 4.9), and the estimated time from the initial prescription until the diphenhydramine cohort returned to baseline risk was 32.3 days (CL 26.9, 37.6).

Conclusions

If these associations are causal, the percentage of the injuries attributable to diphenhydramine was 55% (CL 41, 65), implying a substantial number of excess injuries and costs incurred as the result of diphenhydramine use. The high use rates of this drug and the high incidence of injury suggest that further study of the association between injury and type of antihistamine is needed.

REFERENCES (31)

  • A Stevens et al.

    Drugs affecting postural stability and other risk factors in the hip fracture epidemic – a case-control study

    Comm Med.

    (1989)
  • SG Leveille et al.

    Psychoactive medication and injurious motor vehicle crashes involving older drivers

    Epidemiology

    (1994)
  • TD Koepsell et al.

    Medical conditions and motor vehicle collisions injuries in older adults

    J Am Geriatr Soc

    (1994)
  • M Gilmore et al.

    Occupational injuries and medication use

    Am J Industrial Med

    (1996)
  • TJ Witek et al.

    Characterization of daytime sleepiness and psychomotor performance following H1 receptor antagonists

    Ann Allergy Asthma Immunol

    (1995)
  • Cited by (45)

    • Diphenhydramine: Time to Move on?

      2022, Journal of Allergy and Clinical Immunology: In Practice
    • Association between childhood allergic disease, psychological comorbidity, and injury requiring medical attention

      2014, Annals of Allergy, Asthma and Immunology
      Citation Excerpt :

      Further, recent studies have found that allergic disorders are associated with increased mental health comorbidity.6,7 Impaired sleep,8,9 sedating antihistamines,10,11 and mental health disorders12–19 have been associated with unintentional injury. Therefore, it is logical that patients with allergic disorders are at increased risk for unintentional injury.

    • The diagnosis and management of acute and chronic urticaria: 2014 update

      2014, Journal of Allergy and Clinical Immunology
    • Allergy/respiratory and cardiovascular drugs

      2010, Sleep Medicine Clinics
      Citation Excerpt :

      In addition, controlled studies evaluating psychomotor skills, memory, attention, and actual driving performance confirm that the first-generation H1 antagonists impair performance whereas the second-generation drugs are much less likely to do so.44,52–54 First-generation drugs have been associated with injuries55,56 and traffic accidents57 as well. Even when administered at night, sedation and psychomotor impairment may be present the following morning.58

    View all citing articles on Scopus

    The research project was supported by Schering Corporation, which had no editorial control over the decision to publish the findings or the content of the manuscript.

    View full text