Should diphenhydramine (Benadryl) be avoided in a patient with epilepsy?

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Last updated: February 24, 2025View editorial policy

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From the Guidelines

Diphenhydramine should be used with caution in patients with epilepsy, and alternative medications should be considered when possible. When considering the use of diphenhydramine in patients with epilepsy, it is essential to weigh the potential benefits against the risks, particularly the risk of lowering the seizure threshold and the sedative effects that could mask post-ictal symptoms 1. The most recent and highest quality study, published in 2024, does not directly address the use of diphenhydramine in epileptic patients but emphasizes the importance of careful management of seizures and the consideration of individual patient factors in treatment decisions 1. Given the potential risks, alternative medications such as non-sedating antihistamines (e.g., loratadine or cetirizine) for allergy relief, or melatonin for sleep aid, are preferred 1. If diphenhydramine must be used, starting with a lower dose (e.g., 25 mg instead of 50 mg) and closely monitoring the patient for any increase in seizure activity or changes in seizure patterns is recommended 1. Ultimately, the decision to use diphenhydramine in a patient with epilepsy should be made on a case-by-case basis, considering the individual's specific needs, seizure control, and medication regimen, and in consultation with the patient's neurologist when necessary. Key considerations include:

  • The potential for diphenhydramine to lower the seizure threshold
  • The sedative effects of diphenhydramine and their potential to mask post-ictal symptoms
  • The availability and safety profile of alternative medications
  • The individual patient's seizure control and medication regimen
  • The importance of consulting with the patient's neurologist when necessary to make informed treatment decisions.

From the Research

Considerations for Patients with Epilepsy

When managing patients with epilepsy, it is crucial to consider the potential interactions between antiepileptic drugs (AEDs) and other medications, including those used for non-epilepsy conditions.

  • The primary goal of epilepsy treatment is to eliminate seizures while minimizing adverse effects of AEDs 2.
  • The selection of AEDs should be based on the seizure and epilepsy types, the epilepsy syndrome, and the adverse effects associated with the drug 2, 3.

Potential Interactions with Diphenhydramine

Diphenhydramine (Benadryl) is an antihistamine that can have sedative and anticholinergic effects.

  • There is no direct evidence in the provided studies regarding the interaction between diphenhydramine and AEDs in patients with epilepsy.
  • However, it is known that certain medications can lower the seizure threshold, and patients with epilepsy should be cautious when taking new medications 4.

General Guidance for Medication Management in Epilepsy

When patients with epilepsy are unable to take their usual oral medications, alternative strategies can be used to maintain seizure control.

  • These strategies include using non-pill oral formulations, intravenous formulations of the patient's home AED(s), benzodiazepine bridges, or alternative intravenous AED(s) 5.
  • The management of focal-onset seizures involves choosing the most appropriate medication based on factors such as adverse-effect profiles, age, possibility of pregnancy, and concomitant diseases and medication 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Treatment of epilepsy in adults.

Epileptic disorders : international epilepsy journal with videotape, 2016

Research

Anesthetic management of the patient with epilepsy or prior seizures.

Current opinion in anaesthesiology, 2010

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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