February 5, 2015

Antihistamines and the Risk of Dementia

The more Benadryl and certain other anticholinergic drugs you take, the greater the risk of mental confusion.

If you take medications such as the OTC antihistamine, Benadryl, at high doses or for long periods of time, you are significantly increasing your risk of dementia. A study just published in the Journal of the American Medical Association helps solidify a connection that has been reported for years, but whose validity had been questioned.

The drugs in question are anticholinergic medications, those that block the effects of the neurotransmitter acetylcholine. They include:

  • Older over-the-counter antihistamines such as Benadryl® and Chlor-Trimeton®
  • Tricyclic antidepressants such as Sinequan®
  • Antimuscarinics, which include bladder control medications such as Ditropan®.

The study estimated that people taking at least 10 mg/day of doxepin (Sinequan), 4 mg/day of diphenhydramine (Benadryl), or 5 mg/day of oxybutynin (Ditropan) for more than three years would be at greater risk for developing dementia.

The first study to show a dose response — increasing risk for developing dementia (and Alzheimer's disease) with increasing use of anticholinergic medications.

How might these findings affect older adults? According to lead researcher, Shelly Gray, “Older adults should be aware that many medications — including some available without a prescription, such as over-the-counter sleep aids — have strong anticholinergic effects. And they should tell their health care providers about all their over-the-counter use. But of course, no one should stop taking any therapy without consulting their health care provider.”

Substitutes are available for older antihistamines and tricyclic antidepressants, said Gray, a professor University of Washington School of Pharmacy and director of its geriatric pharmacy program, but it is harder to find substitutes for medicines used to treat urinary incontinence.

Reports of a link between anticholinergics and dementia go back many years but have often been questioned for reasons including study size, length and quality of evidence. The current research tries to address some of these concerns by being larger, running longer and having better access to pharmaceutical records.

The scientists followed over 3,000 people 65 or older for an average of 7.3 years. It is the first study to show a dose response — increasing risk for developing dementia (and Alzheimer's disease) with increasing use of anticholinergic medications. And it is also the first to suggest that dementia risk linked to anticholinergic medications may persist and may not be reversible, even years after people stop taking these drugs.

“If providers need to prescribe a medication with anticholinergic effects because it is the best therapy for their patient,” Dr. Gray said, “they should use the lowest effective dose, monitor the therapy regularly to ensure it's working, and stop the therapy if it's ineffective.”

And of course, people who purchase their own OTC antihistamines should be aware that they are medications and, like all medications, have side effects.

An article on the study appears in JAMA Internal Medicine.

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