Antihistamines and Dementia Risk: What You Need to Know About Long-Term Use

Many older adults reach for diphenhydramine-better known as Benadryl-to help them sleep or ease allergy symptoms. It’s cheap, easy to find, and works quickly. But what happens when you take it night after night, year after year? A growing body of research suggests this common over-the-counter drug might be doing more than just making you drowsy. It could be quietly affecting your brain in ways that increase dementia risk.

Why First-Generation Antihistamines Are a Concern

Not all antihistamines are the same. There are two main types: first-generation and second-generation. The difference isn’t just about how long they last or how strong they are-it’s about what they do inside your brain.

First-generation antihistamines like diphenhydramine, doxylamine, and chlorpheniramine cross the blood-brain barrier easily. Once inside, they block acetylcholine, a key chemical messenger involved in memory, attention, and learning. This is called anticholinergic activity. It’s why these drugs make you sleepy: they’re dampening brain activity. But when this happens over years, it may wear down cognitive resilience.

Second-generation antihistamines-like loratadine (Claritin), cetirizine (Zyrtec), and fexofenadine (Allegra)-were designed to avoid this. They barely enter the brain. Their anticholinergic effect is so weak it’s nearly negligible. For someone needing daily allergy relief, switching to one of these is a simple, low-risk change.

The Evidence: What the Studies Really Show

In 2015, a major study in JAMA Internal Medicine followed over 3,400 adults aged 65 and older for more than a decade. It found that people who took strong anticholinergic drugs regularly-especially antidepressants, bladder meds, and antipsychotics-had a higher chance of developing dementia. But when they looked specifically at antihistamines, the link disappeared. The risk increase was zero.

That same year, another study tracked nearly 9,000 older adults. It found 3.8% of those using first-gen antihistamines developed dementia, compared to 1% of those using second-gen. At first glance, that sounds alarming. But after adjusting for age, health conditions, and other meds, the difference wasn’t statistically significant. In plain terms: the numbers were too close to say one group was truly at higher risk.

A 2019 follow-up study looked at over 1,000 daily doses of various anticholinergic drugs. Antidepressants? Risk went up 29%. Bladder meds? Risk jumped 65%. Antihistamines? No increase at all. The odds were exactly 1.00-meaning no change.

So why do some headlines scream “Benadryl causes dementia”? Because early studies grouped all anticholinergics together. When you lump together a powerful psychiatric drug with a sleepy-time allergy pill, the signal gets muddy. Later, more precise analyses peeled them apart-and the antihistamine signal faded.

Why Doctors Still Warn Against Them

Even if the direct link to dementia isn’t proven, doctors still tell older adults to avoid first-gen antihistamines. Why?

Because they cause real, immediate problems. Dizziness. Confusion. Dry mouth. Urinary retention. Falls. These aren’t theoretical risks-they’re daily dangers for older adults. One fall can lead to a hip fracture, hospitalization, and a rapid decline in health.

The American Geriatrics Society’s 2023 Beers Criteria, the gold standard for safe prescribing in older adults, gives first-gen antihistamines a hard “Avoid” rating. That’s not because of dementia. It’s because they’re unsafe for the body right now.

The European Medicines Agency agrees. Their 2022 update says antihistamines should carry warnings about “potential long-term cognitive effects,” even if the evidence isn’t conclusive. Why? Because the risk is low but the population is huge. Millions take these daily. Even a tiny increase in harm adds up.

What About Sleep? Many Use It to Fall Asleep

The biggest reason people take diphenhydramine isn’t allergies-it’s sleep. A 2022 survey found 42% of adults over 65 use OTC antihistamines regularly to help them sleep. And 78% had no idea these drugs have anticholinergic effects.

But here’s the problem: antihistamines don’t improve sleep quality. They just make you drowsy. You might fall asleep faster, but you’ll miss out on deep, restorative sleep stages. Over time, this can make fatigue worse, not better.

There are better options. Cognitive Behavioral Therapy for Insomnia (CBT-I) works for 70-80% of older adults. It teaches you how to reset your sleep rhythm without pills. But access is limited. The average wait for a CBT-I therapist is over eight weeks. And Medicare only pays $85-$120 per session-far less than what most providers charge.

Low-dose doxepin (Silenor) is a prescription sleep aid with minimal anticholinergic activity. It’s FDA-approved for insomnia and has an ACB score of 1-much safer than diphenhydramine’s score of 3. But it’s not cheap, and many doctors don’t think to prescribe it.

What Should You Do?

If you or a loved one is taking diphenhydramine or doxylamine regularly, here’s what to do:

• Check the label. Look for “diphenhydramine,” “doxylamine,” or “anticholinergic” on the Drug Facts panel. Many sleep aids and cold meds hide them under “inactive ingredients.”
• Switch to second-gen. For allergies, try loratadine, cetirizine, or fexofenadine. They work just as well without the brain fog.
• For sleep, try non-drug options first. Keep a regular bedtime. Avoid screens an hour before bed. Get daylight in the morning. Try a white noise machine.
• Ask your doctor about CBT-I. Even if it’s hard to find, it’s the most effective long-term fix for insomnia.
• Review all meds every six months. Many older adults take 5-10 pills daily. One of them might be contributing to brain fog.

The Bigger Picture: Why This Matters

This isn’t just about one drug. It’s about how we treat aging. We’ve normalized using pills to fix symptoms-drowsiness, insomnia, allergies-without asking whether they’re safe over time. We don’t think twice about taking a sleeping pill for years, but we’d never take a painkiller daily for decades without checking for liver damage.

The same logic should apply here. Just because something is sold over the counter doesn’t mean it’s harmless. The real danger isn’t a guaranteed link to dementia-it’s the quiet, cumulative toll of drugs that dull the brain day after day.

New research is underway. The ABCO study, launched in 2023 with $4.2 million in NIH funding, is tracking 5,000 older adults for a decade. It’s the most detailed look yet at how anticholinergics affect cognition over time. Results won’t come until 2033. But in the meantime, we already have enough to make smarter choices.

Frequently Asked Questions

What’s Next?

The FDA is reviewing all anticholinergic drugs for dementia risk, with results expected in 2024. The European Medicines Agency has already updated labels to include cognitive warnings. The American Geriatrics Society will release its 2024 Beers Criteria in June 2024, likely refining its stance on antihistamines.

In the meantime, don’t wait for official guidelines. If you’re taking a first-gen antihistamine daily, talk to your doctor. There are safer, more effective ways to manage allergies and sleep. Your brain will thank you.