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

For years, many older adults have reached for over-the-counter antihistamines like Benadryl to help with allergies, colds, or trouble sleeping. It’s cheap, easy to find, and seems harmless. But what if taking it every night for years could be quietly affecting your brain? New research is raising serious questions about the long-term use of certain antihistamines and their link to dementia.

Not All Antihistamines Are the Same

There are two main types of antihistamines: first-generation and second-generation. The difference isn’t just about price or brand - it’s about what they do inside your brain.

First-generation antihistamines - like diphenhydramine (Benadryl), doxylamine (Unisom), and chlorpheniramine - cross the blood-brain barrier. Once inside, they block acetylcholine, a key chemical your brain uses to form memories and stay alert. This is why they make you drowsy. But that same effect can be dangerous over time.

Second-generation antihistamines - such as loratadine (Claritin), cetirizine (Zyrtec), and fexofenadine (Allegra) - are designed differently. They barely enter the brain. They work just as well for allergies, but without the strong anticholinergic punch. That’s why experts now say these are the safer choice for older adults.

The Evidence: Mixed, But Cautious

A major 2015 study in JAMA Internal Medicine followed over 3,400 people over age 65 for 10 years. It found that those who took strong anticholinergic drugs - including some antihistamines - had a higher risk of dementia. That study helped spark a wave of concern.

But later research painted a more complicated picture. A 2022 study of nearly 9,000 older adults found that while people taking first-gen antihistamines had slightly higher dementia rates (3.83%) compared to those on second-gen (1.0%), the difference wasn’t statistically significant. In other words, it could have been due to chance. Another 2019 study looked at over 100,000 people and found no increased dementia risk from antihistamines alone - but did find clear links with antidepressants and bladder medications.

Then there’s the problem of confounding factors. Many people who take diphenhydramine nightly do so because they have insomnia. And poor sleep itself is linked to cognitive decline. So is the medication causing the problem - or is it the underlying sleep disorder?

A 2023 analysis of UK Biobank data found that when researchers adjusted for sleep issues, the link between antihistamine use and dementia disappeared. That suggests the real issue might be untreated insomnia, not the drug.

Why Experts Still Say: Avoid First-Gen

Despite the mixed evidence, major medical groups are still warning against first-generation antihistamines in older adults.

The American Geriatrics Society’s 2023 Beers Criteria - the gold standard for safe prescribing in seniors - lists diphenhydramine and doxylamine as drugs to avoid in people over 65. They give this rating a Level A evidence strength, meaning the warning is based on strong, consistent data.

Why? Because even if the dementia link isn’t proven beyond doubt, the risks are real. First-gen antihistamines can cause confusion, dizziness, urinary retention, and falls. These aren’t minor side effects. In older adults, a single fall can lead to a broken hip, hospitalization, and a rapid decline in health.

The Anticholinergic Cognitive Burden Scale (ACB) rates diphenhydramine as a level 3 - the highest possible risk. Fexofenadine and loratadine? Level 0. No risk.

What About Sleep? The Real Problem

The biggest reason older adults take Benadryl isn’t allergies - it’s sleep. One 2022 survey found that 42% of adults over 65 use OTC antihistamines nightly to fall asleep. And 78% had no idea these drugs carry anticholinergic risks.

But here’s the truth: antihistamines aren’t good sleep aids. They don’t improve sleep quality. They just make you drowsy. Over time, your brain adapts. You need more to get the same effect. And you lose the natural sleep cycles that restore memory and clear brain toxins.

There are better options. Cognitive Behavioral Therapy for Insomnia (CBT-I) is proven to work better than any pill for long-term sleep improvement. Studies show it helps 70-80% of older adults. The problem? It’s hard to get. Therapists are scarce, and Medicare pays only $85-$120 per session. Many doctors don’t even mention it.

There are also prescription alternatives with low anticholinergic risk, like low-dose doxepin (Silenor), which has an ACB score of 1 - barely any risk. But it’s expensive and not always covered.

What Should You Do?

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

1. Don’t stop cold turkey. Sudden withdrawal can cause rebound insomnia or anxiety.
2. Talk to your doctor or pharmacist. Ask: "Is this drug still necessary? Is there a safer alternative?"
3. Switch to a second-generation antihistamine if you need allergy relief - Claritin or Zyrtec are just as effective.
4. If you’re using it for sleep, ask about CBT-I. Even a few sessions can change your sleep habits for good.
5. Review all medications every 6 months. Many seniors take 5-10 pills daily. Some are no longer needed.

There’s no magic bullet. But small changes - like swapping Benadryl for Zyrtec or asking for a sleep therapist - can make a big difference over time.

The Bigger Picture

Sales of first-gen antihistamines have dropped 24% since 2015, while second-gen sales have grown by nearly 20%. That’s because awareness is rising. The FDA added dementia warnings to prescription anticholinergics in 2021. The European Medicines Agency now requires patient leaflets to mention "potential long-term cognitive effects." But over-the-counter products? Still no clear warnings beyond "may cause drowsiness." That’s a gap. People trust OTC drugs. They think, "If it’s sold on the shelf, it must be safe." But safety isn’t about availability - it’s about long-term impact.

For older adults, the goal isn’t just to avoid dementia. It’s to stay independent, mobile, and alert. A few simple swaps in your medicine cabinet could help you keep your memory - and your freedom - for years longer.

Final Thoughts

It’s easy to dismiss a little blue pill as harmless. But when you’re taking it every night for years, it’s not just a sleep aid - it’s a daily dose of a drug that slows down your brain’s communication system. The science isn’t perfect, but the warnings from top medical groups are clear: avoid first-gen antihistamines in older adults.

There are better ways to manage allergies. There are better ways to sleep. And choosing them now might mean more clarity, more independence, and more years of remembering your grandchildren’s names - not just reaching for the bottle when you can’t sleep.