Can Benadryl cause tardive dyskinesia? (+5 factors)

In this article, we will discuss the Benadryl-induced tardive dyskinesia. We will also discuss the mechanism and different research studies linking Benadryl to tardive dyskinesia. Additionally, we will discuss the factors influencing Benadry-induced tardive dyskinesia and its management.

Can Benadryl cause tardive dyskinesia?

Benadryl may cause tardive dyskinesia in some individuals. However, it is not a very common side effect of this medication. However, different studies have reported the link of Benadryl to involuntary repetitive movements and tardive dyskinesia.

Benadryl is a brand name for an over-the-counter antihistamine medication diphenhydramine. It primarily works by inhibiting the H1 histamine receptors which are responsible for triggering various allergic reactions in individuals.

To a lesser extent, Benadryl has antimuscarinic properties as well. Due to its antihistamine and sedative properties, it is most frequently used in the management of seasonal allergies, runny nose, sleep disturbances, common cold, and hay fever (1).

How can Benadryl cause tardive dyskinesia?

The mechanism by which Bendryl may induce tardive dyskinesia is linked to its anticholinergic properties. Acetylcholine is responsible for modulating the release of dopamine via striatal muscarinic acetylcholine receptors. Blockade of muscarinic receptors inhibits the release of dopamine in the striatum (2).

Benadryl by blocking acetylcholine receptors in the brain may disrupt the delicate balance of neurotransmitters, particularly dopamine, and acetylcholine, contributing to the development of involuntary repititive movements over prolonged use leading to tardive dyskinesia (1).

What are the symptoms of tardive dyskinesia?

Tardive dyskinesia is generally associated with involuntary and repetitive movements, mostly in the face, tongue, and other areas. Common symptoms include of tardive dyskinesia may include:

  • tongue protrusion or twisting
  • rapid eye blinking
  • restlessness
  • hand wringing
  •  jerky movements
  • involuntary movements of the fingers
  • muscle spasms
  • difficulty swallowing

It is important to note that, the frequency and severity of these symptoms may vary from one individual to another. However, if you experience any unusual movements while on Benadryl, it’s essential to consult with a healthcare professional for proper evaluation and management.

What does research suggest?

Tardive dyskinesia is a rare side effect of Benadryl, and only a few cases have reported the development of involuntary movements and subsequent tardive dyskinesia associated with Benadryl.

A research study reported two cases of diphenhydramine overdose that resulted in delirium and involuntary repetitive movements. The patients exhibited symptoms such as confusion, agitation, and involuntary movements, requiring sedation with continuous propofol infusion (3).

A research study reported the development of generalized tardive dyskinesia in individuals who were undergoing chronic neuroleptic therapy.

The occurrence of tardive dyskinesia, a condition characterized by involuntary, repetitive movements, was specifically linked to the administration of diphenhydramine in the outpatients (5).

Another study reported a case of a female who developed involuntary movements and dystonia after using intravenous diphenhydramine for the management of an allergic reaction. The patient was prescribed another medication for reducing involuntary movements, and after monitoring, she was discharged (4).

What factors can contribute to Benadryl-induced tardive dyskinesia?

Various factors may increase the risk of Bendadryl-induced tardive dyskinesia including the patient’s response to medication, underlying health conditions, and concomitant use of medications associated with tardive dyskinesia.

Cumulative Anticholinergic Burden: When Benadryl is used in combination with other medications that have anticholinergic properties, the cumulative anticholinergic burden increases because Benadryl also has some anticholinergic properties.

In these cases, suppression of dopamine levels in the striatum due to low levels of available acetylcholine is associated with the increased risk of tardive dyskinesia (2).

Age: Some individuals may be more susceptible to movement disorders or may have an increased risk of developing tardive dyskinesia due to old age. Elderly patients are more susceptible to the development of tardive dyskinesia, possibly due to changes in the brain and nervous system with age.

Drug interaction: The concomitant use of medications such as first-generation or typical antipsychotics and anticonvulsants with Benadryl is associated with a higher risk of developing tardive dyskinesia.

Underlying medical conditions: Individuals with a history of other movement disorders or neurological conditions may be at a higher risk of developing tardive dyskinesia while taking Benadryl.

Genetics: Genetic predisposition may also increase the risk of developing tardive dyskinesia. Some individuals may have a genetic vulnerability that makes them more susceptible to the side effects of certain medications including Benadryl.

What other drugs cause tardive dyskinesia?

Drug-induced tardive dyskinesia is most frequently reported with the use of certain medications especially those that block dopamine receptors in the brain such as antipsychotics.

However, other medications such as antidepressants, antihistamines, anxiolytics, and anticonvulsants may also increase the risk of tardive dyskinesia.

The incidence of tardive dyskinesia is higher with prolonged use of the medications including (6):

  • procyclidine
  • chloroquine
  • trazodone
  • phenylephrine
  • doxepin
  • meprobamate
  • metoclopramide
  • hydroxyzine
  • sertraline
  • carbamazepine
  • lamotrigine
  • clomipramine
  • amitriptyline

How to manage Benadry-induced tardive dyskinesia?

If you experience tardive dyskinesia or any involuntary movement while taking Benadryl, you should follow these recommendations for its effective management:

Consult your healthcare provider if suspect Benadryl is causing tardive dyskinesia or any of its associated symptoms. They may assess your condition and evaluate if the symptoms you’re experiencing are associated with Benadryl or any other underlying factor.

If Benadryl is the primary cause of tardive dyskinesia, your healthcare provider may adjust the dosage or recommend you to discontinue the medication under his supervision, based on your specific condition.

They may provide alternative medications to Benadryl with lower anticholinergic effects such as non-sedating antihistamines or other medications that do not have significant anticholinergic properties.

Lifestyle modifications including regular exercise, a well-balanced and nutritious diet, stress management, and adequate sleep may play key roles in the prevention and management of tardive dyskinesia. Additionally, avoiding stimulants like caffeine and nicotine is also recommended.

Collaboration with healthcare professionals is essential to tailor these adjustments to individual needs and monitor symptom management effectively.


In conclusion, based on my knowledge and experience, tardive dyskinesia is rarely associated with Benedryl and is more frequent with the use of antipsychotics especially first-generation and atypical antipsychotics.

However, different studies have reported the development of tardive dyskinesia with prolonged use of Benadryl. If you experience any involuntary movements or other symptoms of tardive dyskinesia after taking Benadryl, consult your healthcare provider immediately.

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