How does Benadryl (Diphenhydramine) stop extrapyramidal symptoms (EPS) and dystonic reactions?

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Last updated: March 9, 2025View editorial policy

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From the Guidelines

Benadryl (diphenhydramine) is effective in stopping extrapyramidal symptoms (EPS) and dystonic reactions due to its anticholinergic properties, which help restore the balance between dopamine and acetylcholine in the brain. When antipsychotic medications block dopamine receptors, they create an imbalance between dopamine and acetylcholine in the basal ganglia, leading to EPS symptoms like muscle stiffness, tremors, and abnormal movements. According to the American Academy of Child and Adolescent Psychiatry 1, antiparkinsonian agents, such as Benadryl, may be considered to avoid acute extrapyramidal symptoms, especially in those at risk for acute dystonias or who have a history of dystonic reactions.

The use of prophylactic antiparkinsonian agents, like Benadryl, is particularly important in patients whose compliance may be an issue, such as those who are paranoid or otherwise distrust medication treatments 1. For acute dystonic reactions, the typical dose is 25-50mg of Benadryl given intramuscularly or intravenously for fastest relief, or orally if the symptoms are less severe. Relief usually occurs within 15-30 minutes of administration. Some key points to consider when using Benadryl for EPS and dystonic reactions include:

  • The need for antiparkinsonian agents should be reevaluated after the acute phase of treatment or if doses are lowered, as many patients no longer need them during long-term therapy 1
  • Benadryl's anticholinergic properties can cause side effects like sedation, dry mouth, blurred vision, and potential cognitive impairment in older adults
  • If someone experiences EPS or dystonic reactions, they should contact their healthcare provider, as medication adjustments may be necessary to prevent recurrence of these symptoms

It's also important to note that other treatment options, such as β-blockers and benzodiazepines, may be considered for akathisia, a sense of severe restlessness frequently manifest as pacing or physical agitation, which is commonly seen in patients treated with antipsychotics 1. However, Benadryl remains a commonly used and effective treatment for EPS and dystonic reactions, and its use should be tailored to the individual patient's needs and medical history.

From the Research

Mechanism of Action

Benadryl (Diphenhydramine) is used to stop extrapyramidal symptoms (EPS) and dystonic reactions due to its anticholinergic properties.

  • Diphenhydramine has been shown to be effective in treating EPS and dystonic reactions in various studies 2, 3, 4, 5.
  • The exact mechanism of action is not fully understood, but it is thought to involve the blockade of cholinergic receptors in the brain, which helps to alleviate the symptoms of EPS and dystonic reactions.

Treatment of EPS and Dystonic Reactions

  • Diphenhydramine has been used to treat EPS and dystonic reactions in various clinical settings, including post-anesthetic complications 2, 3 and drug-induced dystonic reactions 5.
  • The drug has been shown to be effective in reducing the severity of symptoms and improving patient outcomes 4.
  • In some cases, diphenhydramine may be used as a first-line treatment for EPS and dystonic reactions, although the choice of treatment may depend on the specific clinical context and patient factors 2, 3.

Comparison with Other Treatments

  • Diphenhydramine has been compared with other treatments for EPS and dystonic reactions, including benzodiazepines and antiparkinsonian drugs 5, 6.
  • The choice of treatment may depend on the specific clinical context and patient factors, as well as the potential side effects and interactions of the different treatments 6.

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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