Is it safe to administer intravenous (IV) diphenhydramine (Benadryl) to a geriatric patient with dementia?

IV Diphenhydramine Should Be Avoided in Dementia Patients

IV diphenhydramine (Benadryl) should not be administered to patients with dementia due to high risk of worsening cognitive impairment, delirium, and functional decline. 1, 2, 3

Why Diphenhydramine Is Contraindicated in Dementia

Anticholinergic Burden and Cognitive Harm

• Diphenhydramine is classified as a strongly anticholinergic medication that should be avoided in elderly patients with dementia or cognitive impairment. 1, 2
• The anticholinergic properties cause broad muscarinic receptor blockade, resulting in negative effects on cognition, vision, urination, constipation, and overall functionality. 1
• Anticholinergic burden is directly associated with decline in cognition, functional status, and activities of daily living (ADL) scores in older patients. 1
• The FDA label explicitly warns that antihistamines are more likely to cause dizziness, sedation, and hypotension in elderly patients (approximately 60 years or older). 4

Delirium Risk

• Geriatric emergency department guidelines explicitly recommend avoiding high-risk medications, specifically identifying anticholinergic medications as causative agents for delirium. 1
• Delirium consequences include increased mortality, morbidity, extended hospital length of stay, and increased potential for lasting functional decline and subsequent need for nursing home placement. 1
• Even a single 200 mg dose of diphenhydramine in a 76-year-old patient with beginning dementia caused severe anticholinergic symptoms and EEG changes lasting two weeks. 5

Real-World Evidence of Harm

• More than one in four older adults with dementia (26.95%) are prescribed potentially inappropriate anticholinergic medications, with diphenhydramine being among the most frequently used. 6
• Approximately 43% of ambulatory care visits for dementia involve prescribing at least one anticholinergic drug, with 10% involving medications with clinically significant anticholinergic activity. 7
• The liabilities associated with anticholinergic medications include injurious falls, episodes of confusion or delirium, emergency department visits, and hospitalizations—all raising the cost of care. 1

What to Use Instead

For Agitated Delirium

• When chemical restraint is absolutely necessary, haloperidol is recommended over benzodiazepines or diphenhydramine for acute treatment of agitated delirium. 1
• Chemical restraint/sedation should be minimized whenever possible, with therapeutic environment and preventative measures prioritized first. 1

For Allergic Reactions

• While diphenhydramine remains appropriate for anaphylaxis management (25-50 mg parenterally), it should never be used alone and is considered second-line to epinephrine. 2
• In dementia patients requiring allergy treatment, the risk-benefit ratio must be carefully weighed, and the shortest possible duration should be used with close monitoring. 2

For Anxiety or Agitation

• SSRIs (citalopram 10 mg daily or sertraline 25-50 mg daily) are first-line pharmacological treatment for anxiety in dementia patients. 3
• Non-pharmacological interventions should always be attempted first, including identifying reversible medical causes (pain, UTI, constipation, urinary retention, dehydration). 3

Critical Monitoring If Diphenhydramine Must Be Used

Immediate Adverse Effects to Monitor

• Evaluate for urinary retention, constipation, dry mouth, blurred vision, and delirium when diphenhydramine is used. 2
• Watch for paradoxical increase in rage and agitation, particularly in vulnerable populations, which cannot be predicted unless previously documented. 2
• Monitor blood pressure for hypotension, especially when given with other CNS depressants. 2
• Continuous monitoring is mandatory until the patient is awake and ambulatory. 2

Duration Considerations

• The 4-6 hour duration of diphenhydramine often exceeds the time needed for behavioral control, potentially extending recovery time and delaying discharge. 2
• Anticholinergic effects on cognition may persist even as systemic drug levels decline. 2

Common Pitfalls to Avoid

• Never combine diphenhydramine with other anticholinergic agents due to additive effects. 2
• Avoid using diphenhydramine as routine sedation or for sleep in dementia patients—this is inappropriate prescribing. 1, 3
• Do not assume that because diphenhydramine is available over-the-counter, it is safe for elderly patients with dementia. 8, 6
• The concurrent use of three or more CNS-active drugs (including diphenhydramine with antidepressants, antipsychotics, or benzodiazepines) significantly increases fall risk and should be avoided. 9