Diphenhydramine (Benadryl) Linked to Increased Dementia Risk, Especially with Long-Term Use

Recent research, including a significant 2015 study published in JAMA Internal Medicine, has found that prolonged use of diphenhydramine an active ingredient in many over-the-counter allergy and sleep medications like Benadryl is associated with a substantially increased risk of developing dementia, including Alzheimer’s disease. The risk rises with cumulative exposure, with individuals taking diphenhydramine for the equivalent of three years or more facing a 54% higher chance of dementia compared to those using it for three months or less.

Diphenhydramine is an anticholinergic drug, which means it blocks acetylcholine, a neurotransmitter important for memory and cognition. Long-term anticholinergic use may cause permanent changes in brain chemistry and neurotransmission pathways, potentially leading to cognitive decline. Older adults are especially vulnerable because the drug stays longer in their system up to 18 hours causing daytime sedation, impaired concentration, and increased risk of falls and accidents.

While the exact biological mechanisms remain under investigation, hypotheses suggest that chronic anticholinergic use may promote the buildup of beta-amyloid plaques, a hallmark of Alzheimer’s, or interfere with the brain’s ability to clear toxic proteins.

Medical experts advise caution, particularly for people over 55, recommending that they consult healthcare providers before using diphenhydramine or similar anticholinergic drugs long term. Safer alternatives, such as second-generation antihistamines (e.g., loratadine or cetirizine), are preferred as they have fewer cognitive side effects.

In summary, while diphenhydramine remains effective for short-term allergy relief and sleep aid, mounting evidence urges careful use, especially among older adults, to minimize potential long-term risks to brain health and dementia development.