Does Benadryl Cause Dementia?

We Don’t Know Yet, But Here’s What We Do Know

Most of us have taken the oral antihistamine Benadryl (diphenhydramine) at some point in our lives. It’s been on the market since 1946, and it’s easy to access: some form of Benadryl is in the over-the-counter (OTC) section at nearly every pharmacy or supermarket.

It’s always been my go-to for minor allergic reactions like hives. But in more recent years, Benadryl is falling out of favor among the medical community due to some of its potential side effects, like drowsiness and confusion.

Benadryl is particularly risky for older adults who are more likely to experience health consequences as a result of these side effects. Here, we’ll discuss Benadryl’s side effects and its association with dementia. Let’s get into it…

How Benadryl Works

Benadryl, known as an antihistamine, works by blocking a chemical in the body called histamine. Blocking histamine helps relieve allergy symptoms like sneezing. But histamine also helps keep you alert and awake. So when Benadryl blocks this chemical in the brain, it can cause profound drowsiness.

Benadryl also blocks acetylcholine, a chemical involved in memory, attention, and muscle control. That’s why Benadryl is also referred to as an anticholinergic. Blocking acetylcholine can cause side effects like dry mouth, constipation, trouble peeing, blurry vision, and confusion.

When used appropriately, Benadryl can be helpful for some people. But for certain groups, especially older adults, it’s often not the best choice. Because of these risks, Benadryl appears on the American Geriatrics Society Beers Criteria, a list of medications that adults aged 65 and older should generally avoid when possible. As we age, our bodies process medications differently, and the brain becomes more sensitive to drugs that block acetylcholine. This makes side effects more likely.

In older adults, side effects like drowsiness, dizziness, and confusion can increase the risk of falls and injuries.

Can Benadryl Cause Dementia?

The short answer: we don’t know for sure.

There’s a biological reason this question comes up. As mentioned, Benadryl blocks acetylcholine, a chemical that plays an important role in memory and thinking. In fact, Alzheimer’s disease involves changes in acetylcholine signaling. Because certain anticholinergics like Benadryl can cross into the brain, it’s biologically plausible that this could affect cognition.

What the Research Shows

One of the most frequently cited studies on this topic is a 2015 observational study published in JAMA Internal Medicine. Researchers followed more than 3,000 adults aged 65 and older who were enrolled in a Group Health plan in Seattle for an average of about seven years. Using pharmacy dispensing records, they examined whether long-term use of anticholinergic medications was associated with dementia.

Importantly, the researchers did not study Benadryl alone. They studied several anticholinergic drugs, including antidepressants, antihistamines (like Benadryl), and overactive bladder medications. But keep in mind that OTC Benadryl purchases may not have been captured in pharmacy dispensing records, so some Benadryl exposures may have been missed.

By the end of the study, about 23% of participants had developed dementia. A significantly higher risk was seen only in people with high anticholinergic exposure, roughly equivalent to taking an anticholinergic daily for more than three years.

Because this was an observational study, it cannot prove that Benadryl, or any of the other anticholinergic medications studied, causes dementia. Observational studies can only identify associations. And, people who take anticholinergic medications may already have factors that raise dementia risk, such as certain medical conditions or chronic sleep problems.

Taken together, the study doesn’t suggest that occasional or short-term use of Benadryl (or other anticholinergics) increases the risk of dementia. But the findings suggest a possible link between daily, long-term anticholinergic use and dementia.

What About Other Studies?

Other observational studies have shown mixed results. One study found a link between anticholinergics and cognitive decline (but not dementia). Another didn’t find a link between antihistamines and dementia. And one meta-analysis (a review of many studies) found an association between anticholinergics and dementia, but it didn’t specifically examine antihistamines. Notably, no randomized controlled trials have tested whether long-term Benadryl use affects dementia risk.

So, what’s the verdict? In short, heavy cumulative exposure to anticholinergics in older adults has been associated with dementia in observational studies, but causation has not been established. And Benadryl itself has not been studied in isolation.

Should You Skip Benadryl?

Newer antihistamines, such as Zyrtec (cetirizine), Claritin (loratadine), and Allegra (fexofenadine), are typically safer options for older adults because they cause fewer side effects, including drowsiness.

Another advantage is that they typically need to be taken only once a day for allergies, unlike Benadryl, which is typically taken every four to six hours. Saline nasal spray and the steroid nasal spray Flonase Allergy Relief (fluticasone propionate) are other OTC options for managing allergy symptoms.

Many people also take Benadryl for sleep. One OTC product, ZzzQuil, is marketed as a sleep aid and contains diphenhydramine, the active ingredient in Benadryl. Certain combination OTC products, such as Tylenol PM, also contain Benadryl. While it may be tempting to use Benadryl’s side effect of drowsiness for sleep, it’s better for older adults to avoid it.

The American Academy of Sleep Medicine also recommends avoiding Benadryl for sleep. Instead, focusing on sleep hygiene may help do the trick if you’re tossing and turning at night. Avoiding caffeine late in the afternoon and going to sleep around the same time each night are a couple of tips. (That said, we know insomnia can be brutal. If it's a persistent problem, it's worth looping in your clinician — there are evidence-based options (like CBT-I) that go well beyond sleep hygiene tips.)

The Bottom Line

Benadryl is an antihistamine and anticholinergic medication that can cause a variety of side effects, especially in older adults. While Benadryl has not been proven to cause dementia, long-term use of strong anticholinergic medications has been linked to increased dementia risk in observational studies.

For older adults, safer allergy medication options are usually preferred, like Zyrtec (cetirizine) or Claritin (loratadine). If your clinician says it’s OK to take Benadryl, it’s best to take it for the shortest time possible and at the lowest dose.

Stay Curious,

Unbiased Science

Reviewed by Amy Gragnolati, PharmD