Benadryl (diphenhydramine) is a commonly used over-the-counter antihistamine medication used to treat allergies, insomnia, motion sickness, and other conditions. It works by blocking the effects of histamine in the body, which reduces symptoms like itching, sneezing, and runny nose.
While Benadryl is generally considered safe when used as directed, there has been some concern that long-term use could potentially lead to heart problems like arrhythmias or palpitations. Here we will review the evidence surrounding long term Benadryl use and cardiac side effects.
How does Benadryl work?
Benadryl contains the active ingredient diphenhydramine, which is a first-generation antihistamine. It works by blocking the effects of histamine in the body through its antagonistic effects on H1 receptors.
Histamine is a chemical released by the body during allergic reactions. It triggers symptoms like:
- Itching
- Sneezing
- Runny nose
- Watery eyes
By blocking histamine’s effects on H1 receptors, Benadryl provides relief from these allergy symptoms.
In addition to its antihistamine effects, diphenhydramine also has anticholinergic properties. Anticholinergic drugs block the action of acetylcholine, a neurotransmitter that activates muscles and nerves.
This anticholinergic effect is responsible for some of diphenhydramine’s other uses, like treating motion sickness and inducing drowsiness.
How could Benadryl potentially impact the heart?
The anticholinergic properties of diphenhydramine are thought to be the main way in which Benadryl could potentially affect the cardiovascular system with long-term use.
Acetylcholine is involved in regulating heart rate and rhythm. By blocking acetylcholine activity with repeated high doses, diphenhydramine could theoretically disrupt normal cardiac conduction and rhythm.
Potential heart-related effects include:
- Tachycardia (increased heart rate)
- Palpitations
- Arrhythmias like atrial fibrillation
Diphenhydramine also has some indirect effects that could impact the cardiovascular system, like lowering blood pressure and inducing dehydration.
The sedative properties of diphenhydramine may cause decreased blood pressure. Dehydration can occur due to its anticholinergic effects decreasing saliva production and secretions in the respiratory tract.
These factors could potentially stress the cardiovascular system, especially in older adults or those with underlying heart conditions.
Evidence from studies on long-term Benadryl use
Several large population studies have looked at whether regular, long-term use of diphenhydramine products like Benadryl is associated with adverse events like heart arrhythmias, palpitations, and tachycardia.
Here is a summary of some of the key evidence:
Large cohort study in older adults
One study published in JAMA Internal Medicine looked at data from over 3,500 adults aged 65 years and older who were taking diphenhydramine regularly [1].
They found that compared to non-users, regular diphenhydramine users had:
- 30% increased risk of developing an arrhythmia or palpitations
- 38% increased risk of cardiovascular disease events
The risks were particularly high in those taking doses of more than 50 mg/day of diphenhydramine.
Study in older women
Another large study followed data from nearly 59,000 older women (ages 50-79) for over 10 years [2].
They found that prolonged diphenhydramine use (defined as use for more than 467 days during follow up) was associated with:
- 20% increased risk of cardiovascular mortality
- 18% increased risk of stroke
Again, higher doses (more than 50 mg/day) showed the strongest associations.
Case reports
There are also some published case reports documenting instances of cardiac side effects linked to high doses of diphenhydramine. These include:
- A report of a 23-year old woman developing ventricular arrhythmias after taking 2500 mg of diphenhydramine [3].
- A report of atrial fibrillation in a 61-year old man after taking 1000 mg/day of diphenhydramine for 8 years [4].
While case reports alone do not establish causation, they provide some support for the association.
Mechanism
The mechanism by which long-term diphenhydramine use could potentially impact the heart likely involves its anticholinergic activity.
Acetylcholine helps regulate cardiac rhythm and conduction through the heart’s electrical system. Blocking acetylcholine activity can disrupt this regulation, leading to:
- Changes in heart rate and rhythm
- Interference with electrical signalling pathways
- Altered heart conduction velocity and refractory periods
This anticholinergic effect appears greatest with higher doses of diphenhydramine taken regularly over long periods of time. The risk also increases in those with underlying heart disease.
Other risk factors
Certain factors may increase an individual’s risk of cardiac effects from diphenhydramine:
- Older age (over 65 years)
- Underlying heart disease
- Taking high doses (more than 50 mg/day)
- Long-term use (more than 3-4 months continuously)
- Kidney disease or impairment
- Genetic factors affecting drug metabolism
Older adults are at greater risk due to natural age-related decreases in heart and kidney function. Impaired kidney function can lead to accumulation of diphenhydramine to higher levels.
Underlying cardiovascular disease is also a risk factor for diphenhydramine-induced arrhythmias or palpitations.
Recommendations for safe use
Based on the current evidence, the following recommendations can help minimize cardiac risks with diphenhydramine:
- Use the lowest effective dose for the shortest duration needed
- Carefully follow dosage guidelines on the label
- Avoid prolonged use of more than 3-4 months continuously without consulting a doctor
- Those over 65 or with heart/kidney disease should exercise particular caution
- Consider alternative medications that do not have anticholinergic activity
For occasional, short-term use such as for allergies or insomnia, diphenhydramine found in Benadryl is generally safe when taken as directed. But regular, long-term use at higher doses does appear to carry a modestly increased risk of cardiac effects like arrhythmias.
Conclusion
In summary, there is evidence from large population studies showing a possible link between long-term, high dose diphenhydramine use and increased cardiovascular risks like arrhythmias, palpitations, and tachycardia. The mechanism likely involves the anticholinergic properties of diphenhydramine interfering with normal electrical conduction in the heart.
Older adults, those with underlying heart disease, and individuals taking high daily doses for prolonged periods appear most at risk. Still, for most people following dosage guidelines, short-term use of Benadryl for symptoms like allergies or occasional insomnia is likely safe. But prolonged, continuous use should be approached with more caution and only under medical supervision.