Anticholinergic Drugs Like Benadryl Linked

What Are Anticholinergic Drugs and Why Are They Concerning?

Anticholinergic medications work by blocking acetylcholine, a neurotransmitter that plays a central role in memory, attention, and muscle control. The class includes a surprisingly broad range of widely used drugs: first-generation antihistamines like diphenhydramine (Benadryl), tricyclic antidepressants such as amitriptyline, bladder medications like oxybutynin, and certain muscle relaxants and motion-sickness drugs. Many are sold over the counter, and patients often take them for years without realizing they share a common pharmacological profile.

Concern about cognitive harm has been building for over a decade. A landmark 2015 study published in JAMA Internal Medicine, led by researchers at the University of Washington, followed more than 3,400 older adults and found that higher cumulative use of strong anticholinergic drugs was associated with a greater risk of dementia. A 2019 JAMA Internal Medicine analysis of UK primary care records reached similar conclusions, particularly for antidepressants, antipsychotics, antiparkinson drugs, bladder antimuscarinics, and antiepileptics in the anticholinergic class.

Which Medications Carry the Highest Risk?

Not all anticholinergic drugs carry equal risk. Clinicians often refer to the Anticholinergic Cognitive Burden (ACB) scale, which rates medications from 1 (mild) to 3 (definite anticholinergic effect with strong cognitive impact). Drugs scoring 3 — including diphenhydramine, doxepin, oxybutynin, and amitriptyline — are the ones most consistently associated with cognitive decline in observational research.

The American Geriatrics Society Beers Criteria, an authoritative list of medications that may be inappropriate in older adults, has long flagged strong anticholinergics as drugs to avoid when possible in patients over 65. The concern is amplified when several mildly anticholinergic drugs are combined, since the cognitive burden is cumulative. Patients taking, for example, an antihistamine for allergies plus a tricyclic for sleep plus a bladder medication may have an overall anticholinergic load that substantially exceeds what any single prescription would suggest.

What Should Patients and Families Do?

Patients should not abruptly stop medications without medical guidance — sudden discontinuation of antidepressants or bladder drugs can cause withdrawal effects or symptom rebound. However, experts recommend a periodic medication review with a physician or pharmacist, particularly for adults over 65. For many anticholinergic indications, safer alternatives exist: second-generation antihistamines like loratadine or cetirizine cause far less central nervous system penetration, SSRIs and SNRIs have largely replaced tricyclics for depression, and beta-3 agonists like mirabegron offer an alternative to anticholinergic bladder drugs.

Public health experts emphasize that the dementia association seen in observational studies does not prove causation, and randomized trials of deprescribing are still limited. But the consistency of the signal, combined with the availability of alternatives for most indications, has shifted clinical practice toward minimizing exposure — especially the use of over-the-counter sleep aids containing diphenhydramine, which are still marketed widely to older adults despite long-standing geriatric concerns.