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Does Popular OTC Antihistamine Increase Risk of Dementia?

Does the antihistamine diphenhydramine (DPH) increase the risk of dementia? What about anticholinergic drugs for overactive bladder (OAB)?
Does Popular OTC Antihistamine Increase Risk of Dementia?
Surprised senior woman trying to close her alarm clock

The Food and Drug Administration has been surprisingly silent about the possible risk of dementia associated with anticholinergic drugs. It has been our observation that once this federal agency approves a medicine for OTC use it has a hard time warning about potential adverse reactions. That’s especially true if the danger is something as scary as the risk of dementia. This reader has a worrisome story to share:

Diphenhydramine (DPH) and Dementia?

Q. I was taking the antihistamine cetirizine every night for allergies and to help with insomnia. My husband was taking Benadryl for better sleep.

When we read that some antihistamines have anticholinergic properties, we immediately stopped the drugs. Within days, we noticed a major difference in brain function. All the “fog” cleared. There was no more “cotton” in the brain. In addition, I could recall names and words that very often escaped me previously.

My mom died of Alzheimer’s and I remember thinking that I might be developing early-onset Alzheimer’s. Why aren’t people warned about the anticholinergic effects of antihistamines?

A. Acetylcholine is a neurotransmitter essential for cognitive function and memory. Anticholinergic drugs interfere with this critical compound.

There are hundreds of medications with anticholinergic effects, including some popular antihistamines. Other drugs with this property include medicines for overactive bladder, Parkinson’s disease, motion sickness, dizziness and some types of breathing problems.

We’re glad that you got such benefit from stopping your antihistamines. Cetirizine is a much weaker anticholinergic drug than diphenhydramine. A review article in the journal Clinical Therapeutics (Nov. 2016) titled “Review of Safety and Efficacy of Sleep Medicines in Older Adults” concluded:

“Diphenhydramine should be avoided in the elderly.”

DPH and the Risk of Dementia:

Others have also expressed their concerns about anticholinergic drugs and dementia:

Q. Both my mother and mother-in-law were diagnosed with Alzheimer’s. Mom was 76, and my mother-in-law was 72.

They lived very different lifestyles: Mom dealt with severe anxiety and depression, while my mother-in-law was a happy-go-lucky, active and vivacious health nut. The only common denominator they shared is that they both took diphenhydramine to sleep. Their doctors advised this!

Recently, an older friend at church said her doctor had advised her to do the same. I cautioned her against it.

Of course, our mothers might have developed Alzheimer’s regardless. I do believe diphenhydramine exacerbated the tendency. We must be our own health care advocates and watch out for our elderly loved ones as well.

Diphenhydramine (DPH) Is Found in Many Places:

A. Diphenhydramine (Benadryl) is an old-fashioned antihistamine that was originally developed to treat allergies. Because it often makes people drowsy, drug companies have added diphenhydramine to over-the-counter sleeping pills. Virtually all “PM” nighttime pain relievers contain this drug.

Diphenhydramine interferes with the action of the brain chemical acetylcholine. Long-term use of strong anticholinergic drugs has been linked to the risk of dementia (BMJ, April 25, 2018).

Doctors, DPH and Dementia:

It worries us that physicians are recommending DPH for insomnia. The authors who reviewed the “Safety and Efficacy of Sleep Medicines in Older Adults” wrote:

“Over-the-counter (OTC) or nonprescription medications such as antihistamines are frequently used for sleep. They are inexpensive and readily available options; however, they have limited data on safety and efficacy when used for insomnia. Diphenhydramine is the most commonly used OTC pharmacologic agent. OTC sleep aids should be utilized in short durations because tolerance can develop.”

What Does That Mean?

The authors go on to state:

“Furthermore, tolerance develops after 1 to 2 weeks of uninterrupted use of the antihistamines, which would render it an ineffective therapy.”

Geriatricians, writing in the American Journal of Medicine (June, 2006), note:

“Antihistaminics, such as diphenhydramine, may be used for their sedating effects. They are associated with cognitive impairment, daytime drowsiness, and anticholinergic effects. There are no specific data to show that antihistamines either improve insomnia or prolong sleep, and in general, these medications are avoided in the elderly because of potential side effects.”

There has been growing evidence that prolonged exposure to strong anticholinergic drugs has been associated with an increased risk of dementia.

Other Anticholinergic Drugs:

We suspect that many health professionals are unaware of the medications (both prescription and OTC) that have significant anticholinergic activity. Many are included in something called the Beers Criteria. These are medicines that should specifically be avoided by people over 65. The list was named after geriatrician, Mark Beers, MD. He was concerned that inappropriate drugs were being prescribed to older people far too frequently.

“According to the updated Beers criteria, diphenhydramine in particular should not be used as a sedative-hypnotic in the elderly.” (“Management of Chornic Insomnia in Elderly Persons” in The American Journal of Geriatric Pharmacotherapy, June, 2006).

In other words, older people (those over 65) should not use DPH as a sleeping pill. And yet the FDA has not been proactive in warning older people to stay away from PM pain relievers or other OTC drugs containing DPH. We find this disheartening.

We suspect that many of the purchasers of pain relievers containing diphenhydramine are are over 65. That would be especially true if their physicians recommend DPH for insomnia on the grounds that it is safer than prescription sleeping pills.

You can read other stories at this link:

Will Sleeping Pill with Diphenhydramine Lead to Memory Loss?

Other Anticholinergic Drugs and Dementia:

Many of the medicines prescribed for “overactive bladder” (OAB) have strong anticholinergic activity. An article published in the journal European Urology Focus (Nov. 3, 2021) compared classic anticholinergic drugs for OAB against mirabegron (Myrbetriq), which has a different mechanism of action:

 “Older adults receiving solifenacin and darifenacin in the 6 mo prior to diagnosis, and those receiving solifenacin, darifenacin, tolterodine, or fesoterodine in the year prior to diagnosis, have increased odds of incident dementia, compared with those receiving mirabegron.

“In a large Canadian cohort of patients who developed dementia after starting an overactive bladder (OAB) medication, those taking some anticholinergic medications for OAB have an increased risk of dementia compared with those taking mirabegron.”

Other studies have also suggested that anticholinergic drugs used to treat OAB increase the risk for dementia (BJU International, July, 2020; International Brazilian Journal of Urology, July-August, 2021). Doctors and the FDA need to start paying closer attention to the potential dangers of medications with anticholinergic activity.

Where Can you Learn More?

Share your own story about DPH or other drugs that might increase the risk of dementia in the comment section below. There are other strategies to ease insomnia. You will find them in our eGuide to Getting a Good Night’s Sleep, available in the Health eGuides section of this website. You can also find a list of anticholinergic drugs at this link.

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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.” .
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