Can Benadryl (Diphenhydramine) cause delirium?

From the Guidelines

Benadryl (diphenhydramine) can cause delirium, especially in older adults or at high doses. This antihistamine medication crosses the blood-brain barrier and blocks acetylcholine, a neurotransmitter important for cognitive function, which can lead to confusion, disorientation, hallucinations, and other symptoms of delirium. The risk is particularly high in elderly patients, those with dementia, or individuals with certain medical conditions. Although the provided evidence does not directly link Benadryl to delirium, the mechanism of action and clinical experience suggest a potential risk 1.

Key Considerations

• Standard doses (25-50mg) may cause mild cognitive effects in sensitive individuals, while higher doses significantly increase delirium risk.
• Symptoms typically resolve within 24-48 hours after stopping the medication.
• If delirium occurs, discontinue Benadryl immediately and consult a healthcare provider.
• For allergy treatment, consider non-sedating antihistamines like cetirizine (Zyrtec) or loratadine (Claritin) as safer alternatives, especially for older adults.
• For sleep issues, non-pharmacological approaches or discussing other medication options with a healthcare provider is recommended rather than using Benadryl regularly.

Prevention and Management

• Identify delirium risk factors: dementia, hypertension, alcohol abuse, high severity of illness, coma; benzodiazepine administration 1.
• Avoid benzodiazepine use in those at risk for delirium.
• Mobilize and exercise patients early.
• Promote sleep (control light; noise; cluster patient care activities; decrease nocturnal stimuli) 1.
• Restart baseline psychiatric meds, if indicated.

Given the potential risks, it is recommended to use Benadryl with caution and consider alternative treatments, especially in older adults or individuals with risk factors for delirium 1.

From the FDA Drug Label

Warnings When using this product • marked drowsiness may occur • excitability may occur, especially in children

The FDA drug label mentions excitability as a possible effect, especially in children, but it does not directly mention delirium.

• Drowsiness is also mentioned as a possible effect. Since the label does not explicitly mention delirium, no conclusion can be drawn about its relationship to Benadryl (Diphenhydramine) use 2.

From the Research

Delirium and Diphenhydramine

• Delirium is a serious condition that can be caused by various factors, including medication side effects 3.
• Diphenhydramine, an antihistamine, can cause delirium, especially in combination with other medications such as linezolid 3.
• The combination of diphenhydramine and linezolid has been reported to cause delirium with hallucinations in a 56-year-old man 3.
• The Naranjo probability scale suggests a possible relationship between the reaction and the combination of diphenhydramine and linezolid 3.

Treatment of Delirium

• The treatment of delirium depends on addressing its underlying cause, and antipsychotics are often used to manage symptoms 4, 5.
• Benzodiazepines are not recommended for the treatment of delirium, as they may induce delirium (paradox reaction) or worsen symptoms 4, 6, 7.
• There is limited evidence to support the use of benzodiazepines in the treatment of delirium, and further research is required to determine their role in managing this condition 6, 7.

Medications to Avoid in Delirium

• Certain medications, such as sedating antipsychotics (e.g., prothipendyl, promethazine, levomepromazin), are considered inappropriate for use in the elderly due to their anticholinergic and orthostatic side effects 4.
• Chloral hydrate is also considered inappropriate medication in the elderly due to QTc-prolongation 4.
• Diphenhydramine, due to its potential to cause delirium, should be used with caution, especially in combination with other medications 3.