Does Diphenhydramine (Benadryl) increase the risk of seizures?

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Last updated: April 28, 2025View editorial policy

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From the Guidelines

Benadryl can increase the risk of convulsions, particularly in individuals with a history of seizures or epilepsy. This is based on the guidance provided by the British Thoracic Society guidelines for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD) 1, which cautions against the use of certain medications in patients with a history of seizures due to the increased risk of convulsions.

Key Considerations

  • The risk of convulsions associated with Benadryl is particularly relevant for individuals with epilepsy or a history of seizures, as noted in the guidelines 1.
  • While the guidelines do not specifically discuss Benadryl, the caution against increased risk of convulsions in patients with epilepsy/history of seizures can be applied to the use of Benadryl, given its potential to affect brain neurotransmitters and lower the seizure threshold.
  • It is essential to use Benadryl with caution in vulnerable individuals, such as those with epilepsy, and to monitor for adverse effects closely, as recommended for patients with renal impairment or liver disease 1.

Clinical Implications

  • Patients taking Benadryl should be advised to report any symptoms of neurological effects, such as confusion, agitation, hallucinations, or muscle twitching, immediately.
  • Healthcare providers should carefully weigh the benefits and risks of using Benadryl in patients with a history of seizures or epilepsy, considering alternative treatments when possible.
  • The mechanism behind the increased seizure risk involves diphenhydramine's effects on brain neurotransmitters, particularly its ability to block histamine and acetylcholine receptors, which can disrupt normal brain electrical activity at excessive levels.

From the Research

Benadryl and Convulsions

  • There is evidence to suggest that Benadryl (diphenhydramine) may increase the risk of convulsions, particularly in cases of overdose 2.
  • A study published in 2021 found that antihistamines, including diphenhydramine, were a common cause of new-onset seizures 3.
  • Another study reported a case of status epilepticus and wide-complex tachycardia secondary to diphenhydramine overdose, highlighting the potential for severe neurological complications 2.
  • However, it is worth noting that the majority of patients who experience seizures or convulsions due to diphenhydramine overdose have normal renal function and are taking the medication at therapeutic doses 3.

Mechanism of Action

  • Diphenhydramine is an H1 histamine antagonist that can cause anticholinergic and antihistaminergic effects, as well as sodium channel blockade in cases of overdose 2.
  • The exact mechanism by which diphenhydramine increases the risk of convulsions is not fully understood, but it is thought to be related to its effects on the central nervous system 4, 3.

Clinical Implications

  • Healthcare providers should be aware of the potential for diphenhydramine to cause convulsions, particularly in patients with a history of seizure disorders or those taking other medications that may lower the seizure threshold 4, 3.
  • Patients taking diphenhydramine should be monitored closely for signs of neurological complications, including seizures and status epilepticus 2.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Antihistamines as a common cause of new-onset seizures: a single-center observational study.

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 2021

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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