Is hydroxyzine recommended over Benadryl (diphenhydramine) in the elderly?

Hydroxyzine is NOT Recommended Over Benadryl in the Elderly—Both Should Be Avoided

Neither hydroxyzine nor diphenhydramine (Benadryl) should be used in elderly patients due to their equally problematic anticholinergic properties and associated risks of cognitive impairment, delirium, falls, and mortality. 1

Why Both Medications Are Inappropriate in Older Adults

Equivalent Anticholinergic Burden

• Both diphenhydramine and hydroxyzine are first-generation antihistamines with significant anticholinergic activity that causes cognitive impairment, delirium, and sedation in elderly patients 1
• The American Geriatrics Society explicitly identifies both diphenhydramine and hydroxyzine as medications that should be avoided postoperatively in older adults to prevent delirium (strong recommendation) 1
• Laboratory measurements show diphenhydramine has anticholinergic activity of 5-15 pmol/mL atropine equivalents at therapeutic doses, placing it in the moderate-to-high risk category 2
• Hydroxyzine demonstrates similar problematic anticholinergic effects with 80% sedation rates compared to diphenhydramine's 50% 1

Specific Risks in the Elderly Population

• Cognitive decline and delirium: Both medications cause significant cognitive impairment, with effects more pronounced in patients over 75 years of age 3
• Falls and fractures: Anticholinergic medications significantly increase fall risk, leading to fractures and subdural hematomas 1, 3
• Functional decline: Long-term use causes decreased activities of daily living (ADL) scores 1, 3
• Cardiovascular complications: Both can worsen hypertension and cause cardiovascular events, particularly concerning in MCAS patients prone to such events 1
• Urinary retention and constipation: Anticholinergic effects on bladder and bowel function are particularly problematic in elderly patients with pre-existing prostatic hypertrophy or decreased mobility 1, 3

Preferred Alternatives: Second-Generation Antihistamines

When antihistamine therapy is needed in elderly patients, second-generation agents should be used instead. 1

Recommended Options

• Cetirizine, fexofenadine, loratadine, or desloratadine are preferred due to minimal anticholinergic effects and reduced CNS penetration 1, 4
• These agents provide effective histamine blockade without the cognitive impairment, sedation, and anticholinergic toxicity of first-generation antihistamines 1, 4
• Second-generation antihistamines can be safely used at 2-4 times FDA-approved doses when needed for conditions like mast cell activation syndrome 1

Clinical Considerations

• Cetirizine and levocetirizine require dose adjustment (halved) in moderate-to-severe renal impairment 1
• Fexofenadine demonstrates particularly low brain H1 receptor occupancy, minimizing sedation risk 4
• These agents do not impair driving ability or work performance, unlike first-generation antihistamines 1

Important Caveats

Limited Exceptions for First-Generation Antihistamines

• Acute severe allergic reactions or anaphylaxis: Diphenhydramine may be necessary for severe allergic or transfusion reactions where rapid effect is critical 1
• Even in these situations, the medication should be discontinued as soon as the acute situation resolves 1

Polypharmacy Concerns

• Approximately one-third of independent-living older adults and half of those in long-term care take medications with anticholinergic properties that may be unnecessary 3
• The cumulative anticholinergic burden from multiple medications significantly increases adverse outcomes 3, 5
• Regular medication review to identify and reduce anticholinergic burden is essential in elderly patients 1, 3

Monitoring Requirements

• If first-generation antihistamines must be used temporarily, monitor closely for confusion, falls, urinary retention, and constipation 1, 3
• Consider using validated cognitive screening tools (Mini-Mental State Examination or Montreal Cognitive Assessment) to detect early cognitive decline 3

The bottom line: There is no advantage to choosing hydroxyzine over diphenhydramine in elderly patients—both carry equivalent risks and should be replaced with second-generation antihistamines whenever possible. 1