Steven M. Hernandez, PharmD candidate at the University of Rhode Island, wrote key pieces of this document and his contribution is hereby acknowledged.

Diphenhydramine (Benadryl and others) is an older and presumably sedating antihistamine, widely used as a sedative-hypnotic, especially in the elderly. A recent event at the MGH suggests that the use of diphenhydramine for this purpose should be re-examined.

A prospective study of the clinical use of diphenhydramine, conducted by Agostini et al at Yale University and New Haven Hospital, suggested the use of diphenhydramine might not only be problematic for the elderly, but for others as well.¹ The indications for the use of diphenhydramine in elderly hospitalized patients in the study were:

There was a 70% increased risk of decline in cognitive function in the group that received diphenhydramine. The risks of cognitive dysfunction appeared to be dose-related, using the Confusion Assessment Method (CAM) and the Folstein Mini-Mental State Exam (MMSE). Other observations included increase in urinary catheterization (RR 2.5) and an increase in length of hospital stay (median of 7 vs. 6 days).

Contrary to popular belief, there are no data to suggest that diphenhydramine is an effective sedative-hypnotic in the elderly. However, older patients are sensitive to the negative cognitive effects of the drug and to its anticholinergic effects, such as decreased alertness, dry mouth, blurred vision, increased anxiety, urinary retention and arrhythmias.^2,3

The Drug Therapy Committee suggests the following:

• Diphenhydramine should not be used as a sedative-hypnotic, especially in elderly patients.
  Many routine order sets list diphenhydramine as a "prn" medication. These orders should be discontinued from all order sets. The Drug Therapy Committee, after consultation with geriatricians, recommends oxazepam (Serax) 10-15mg as an alternative in elderly patients. Trazodone 50mg at bedtime is another choice. Other drugs, including other benzodiazepines, have been associated with significant cognitive dysfunction in the elderly. Zolpidem (Ambien) has also been shown to produce cognitive dysfunction and falls when used in this population.⁴
• Diphenhydramine should not be used for prophylaxis for blood transfusion unless there is a history of previous reactions. Because of the likelihood of side effects and the lack of benefit, this practice appears to be unjustified.

The Drug Therapy Committee has approved the addition of fexofenadine (Allegra) as a non-sedating antihistamine for general use.

References:

1. Agostini JV, Leo-Summers LS, SK Inouye. Cognitive and other adverse effects of diphenhydramine use in hospitalized older patients. Arch Intern Med. 2001; 161(17): 2091-7.
2. Simons FER, Simons KJ. Drug therapy: the pharmacology and use of H₁-receptor-antagonist drugs. New Engl J Med. 1994; 330(23): 1663-70.
3. Mintzer J, Burns A. Anticholinergic side-effects of drugs in elderly people. J R Soc Med. 2000; 93(9): 457-62.
4. Langtry HD, Benfield P: Zolpidem. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential. Drugs 1990; 40:291-313.