Imagine waking up and feeling like your face is a leaky faucet, your eyes are itchy cotton balls, and your nose is auditioning for a sneezing competition. That’s what allergies feel like—your immune system throwing a tantrum over harmless stuff like pollen, dust, or your neighbor’s cat. Your throat might get scratchy, your eyes water like you’re watching a sad movie, and your brain feels foggy from lack of sleep because you spent all night battling a stuffy nose. It’s not quite a cold, not quite the flu—just your body overreacting to spring or that innocent-looking patch of grass. Add in a few mystery rashes or the occasional wheezy breath, and allergies become an annoying, sneezy rollercoaster that won’t let you off until the season changes or the antihistamines kick in. Unfortunately, research has shown that the first generation of antihistamines, which contain the active ingredient diphenhydramine, have been linked to dementia.
- What is Diphenhydramine?
Diphenhydramine is an antihistamine that is commonly used to:
- Relieve allergy symptoms (runny nose, sneezing, itching)
- Act as a sleep aid (often found in OTC products like ZzzQuil, Tylenol PM)
- Relieve motion sickness or nausea
It belongs to a class of drugs called first-generation antihistamines, which cross the blood-brain barrier and have strong anticholinergic effects.
- What Does “Anticholinergic” Mean—and Why Does It Matter?
Anticholinergic drugs block acetylcholine, a key neurotransmitter involved in:
- Memory and learning
- Muscle activation
- Cognitive processing
While short-term use of these medications may cause temporary symptoms like confusion or drowsiness, long-term use has been associated with chronic cognitive decline.
- Evidence Linking Diphenhydramine to Dementia Risk
► The JAMA Internal Medicine Study (2015)
- Conducted by researchers at the University of Washington.
- Followed 3,434 adults aged 65+ over a 10-year period.
- Those with higher cumulative use of strong anticholinergics—including diphenhydramine—had a significantly increased risk of developing dementia.
- Even people who had stopped using the drugs years earlier still showed increased risk.
► Meta-Analysis of 14 Studies (2021)
- Included over 1.5 million participants.
- Found that both low and high cumulative anticholinergic use was linked to:
- Increased risk of all-cause dementia
- Increased risk of Alzheimer’s disease
- The longer and more frequently the drugs were used, the higher the risk.
► Mechanistic Support
- Imaging studies and autopsies suggest anticholinergic drugs reduce brain volume and decrease glucose metabolism in areas responsible for memory and learning—changes also seen in Alzheimer’s patients.
- Who Is Most at Risk?
- Older adults (65+) are particularly vulnerable due to natural declines in acetylcholine production.
- Women may be more affected, possibly due to hormonal influences on neurotransmitter activity.
- Individuals with existing cognitive impairment or family history of dementia may also be at greater risk.
- Occasional vs. Chronic Use: Is It Safe in Small Doses?
Most of the risk appears to be dose- and duration-dependent:
- Occasional or short-term use (e.g., for seasonal allergies or travel) is unlikely to significantly increase dementia risk.
- Chronic use, especially as a nightly sleep aid, raises concern.
A single tablet every now and then is not the issue—it’s the cumulative anticholinergic burden over months or years.
- Safer Alternatives to Diphenhydramine
► For allergies:
- Loratadine (Claritin)
- Fexofenadine (Allegra)
- Cetirizine (Zyrtec)
→ These are second-generation antihistamines, which do not cross the blood-brain barrier easily, and thus have minimal cognitive side effects.
► For sleep:
- Melatonin: Natural sleep-wake regulator with minimal side effects when used appropriately.
- Cognitive Behavioral Therapy for Insomnia (CBT-I): Considered the gold standard for chronic sleep issues.
- Herbal remedies like valerian root or magnesium glycinate (consult a healthcare provider before starting).
- What You Should Do If You Use Diphenhydramine Regularly
- Review your medication use—not just diphenhydramine but also other drugs with anticholinergic activity (some antidepressants, bladder medications, etc.).
- Talk to your doctor about the risks and possible alternatives, especially if you are:
- Over age 60
- Using the drug daily or nightly
- Having trouble with memory or focus
- Consider a medication review with a pharmacist trained in geriatric care (a “deprescribing” consultation).
Diphenhydramine is effective in the short term for allergies and sleep, but its anticholinergic effects make it risky for long-term use—especially in older adults. A growing body of research suggests a significant association between chronic use and dementia, particularly when combined with other similar medications.
If you or a loved one is using diphenhydramine regularly, it’s worth reevaluating with a healthcare professional. There are safer, modern alternatives that don’t carry the same neurological risks.
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