How Tylenol PM, Benadryl, and Other Over-the-Counter Drugs May Increase Dementia Risk

Common over-the-counter medications like Benadryl and Tylenol PM contain anticholinergic drugs that may increase dementia risk with long-term use. Learn the science, risks, and safer alternatives.

It’s a common scenario: you grab an over-the-counter (OTC) medication to relieve allergies, fall asleep faster, or treat cold symptoms. While these products offer quick relief, many contain a class of drugs that researchers have linked to long-term cognitive decline—anticholinergic medications.

What Are Anticholinergic Drugs?

Anticholinergic drugs block acetylcholine, a crucial neurotransmitter involved in learning, memory, and muscle control. When acetylcholine is suppressed—especially over time—side effects can impact both the body and brain.

Why Should You Be Concerned?

Mounting evidence suggests that prolonged use of strong anticholinergic medications increases the risk of dementia, including Alzheimer’s disease, especially in older adults. This risk isn't tied to occasional use but rather long-term, cumulative exposure.

Common OTC Medications With Anticholinergic Effects

Many popular OTC drugs contain diphenhydramine, a well-known anticholinergic compound. These include:

• Allergy Medications: Benadryl and other diphenhydramine-based antihistamines

• Sleep Aids: Unisom, Tylenol PM, Advil PM

• Cold & Flu Remedies: Multi-symptom products that also promote sleep

Prescription Drugs Can Also Contribute

Beyond OTC remedies, several prescription medications carry anticholinergic properties:

• Antidepressants: Tricyclics like amitriptyline and doxepin

• Antipsychotics

• Bladder medications: Oxybutynin, tolterodine

• GI medications: Some antispasmodics and anti-nausea drugs

These can build up what's known as your anticholinergic burden—the combined effect of all anticholinergic medications you’re taking.

What the Research Says

Study #1 – 2015 JAMA Internal Medicine

• Followed 3,500+ seniors for over 10 years

• Long-term users of strong anticholinergics had a 60% higher risk of dementia

• Risk increased with cumulative dosage

Reference: Gray et al. (2015), JAMA Internal Medicine, 175(3):401-407 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2110967

Study #2 – 2019 JAMA Internal Medicine

• Included over 284,000 adults in the UK

• Found a strong association between high anticholinergic exposure and later dementia diagnosis

Reference: Savva et al. (2019), JAMA Internal Medicine, 179(5):673-682 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2723671

Why the Risk? Possible Mechanisms

• Chronic acetylcholine suppression impacts memory and learning

• Brain changes like reduced volume and Alzheimer’s markers

• Neuroinflammation, a potential driver of neurodegenerative disease

Who Is Most At Risk?

• Older Adults: Natural decline in acetylcholine levels and slower drug metabolism

• People on Multiple Medications: Risk increases with combined anticholinergic use

• Those Using Long-Term Sleep Aids or Allergy Meds: Prolonged use is especially concerning

Safer Alternatives to Anticholinergic Drugs

For Allergies:

• Non-sedating antihistamines: Claritin (loratadine), Zyrtec (cetirizine), Allegra (fexofenadine)

For Sleep:

• Behavioral treatments: Cognitive Behavioral Therapy for Insomnia (CBT-I)

• Melatonin: Considered safer for short-term use

For Cold Relief:

• Non-anticholinergic treatments: Saline sprays, acetaminophen, ibuprofen, rest, hydration

What You Can Do

• Review your medications with your healthcare provider

• Ask about alternatives to reduce anticholinergic burden

• Read ingredient labels on OTC products—watch for diphenhydramine and terms like “PM”

• Don’t stop medications abruptly—always consult your doctor

Final Thoughts

The link between anticholinergic medications and dementia risk is too significant to ignore—especially for older adults. Fortunately, safer options exist, and making informed choices now may protect your brain health in the future.

🧠 Common Medications With Strong Anticholinergic Ingredients

✅ Safety Tips:

• Watch for "diphenhydramine" and "doxylamine" in ingredient lists.

• Products labeled “PM”, “nighttime”, or “sleep aid” often include these.

• Review medications with your doctor or pharmacist—especially if you’re 65+ or take multiple medications.