Over-the-counter sleeping pills may not be as safe as we thinkSome insomniacs are leery of prescription sleeping pills but feel OK about sleep aids sold at the drugstore.

“I’m not really looking for medical intervention,” said Dale, a marketing manager who spoke to me about his insomnia as I was conducting interviews for my book. “I’m absolutely not interested in anything strong. But if it’s sold over the counter and I can take a half dose of it, that’s fine.”

Many of us assume that over-the-counter drugs are safer than prescription drugs. Yet the long-term effects of any drug can remain unknown for decades, and now researchers have found a correlation between long-term and/or high-dose use of OTC sleep aids and dementia.

Which Drugs Are Involved?

These drugs are called anticholinergics, among them the first-generation antihistamines that are now marketed as sleep aids. The active ingredient in these sleep aids is diphenhydramine or doxylamine. Here’s a list of common brand names:

  • Benadryl
  • Sominex
  • ZzzQuil
  • Tylenol PM
  • Excedrin PM
  • Nytol
  • Unisom
  • Store brands containing diphenhydramine and doxylamine.

Anticholinergic drugs block the action of acetylcholine, a neurotransmitter that plays an important role in waking us up and keeping us vigilant. When we’re awake, acetylcholine neurons are active in several areas of the brain. But the brains of people with Alzheimer’s disease show a marked reduction of acetylcholine and acetylcholine-secreting nerve cells. Other common anticholinergic medications include tricyclic antidepressants such as doxepin (Sinequan) and antimuscarinic drugs for bladder control such as oxybutynin (Ditropan).

Gist of the Study

Investigators at the University of Washington began tracking the medical records of 3,434 healthy 65-year-olds to see if anticholinergic medications increased their risk of developing dementia. About 23 percent of these older adults went on to develop dementia over a 7-year period.

Compared with people who did not take anticholinergic drugs, people taking at least 4 mg of diphenhydramine daily (1 capsule of Benadryl or ZzzQuil contains 25 mg of diphenhydramine), 10 mg of doxepin daily, and 5mg of oxybutynin for more than 3 years had a small increased risk of developing dementia. The risk increased in a linear fashion with higher doses and longer use.

Results in Perspective

This is not the first study to link dementia to the use of anticholinergic drugs. Researchers in Australia found that taking more anticholinergic medications was associated with greater risk of hospitalization for confusion or dementia. Researchers in Spain have concluded that long-term use of anticholinergic drugs “may generate a worsening of cognitive functions” and can also “initiate signs of dementia.”

None of the studies show that the relationship between anticholinergics and dementia is causal. Yet they do suggest that frequent use of OTC sleep aids may not be as harmless as many insomniacs suppose.

So what to do? Several prescription sleeping pills have also been connected to an increased risk of dementia, and a small body of research suggests that poor sleep may itself be a factor in the development of cognitive impairment. Now is the time to check into drug-free treatments for insomnia and be more sparing in the use of sleep meds, whether they’re handed over by a pharmacist or you can buy them right off the shelf.


Posted by Lois Maharg, The Savvy Insomniac

Lois Maharg has worked with language for many years. She taught ESL, coauthored two textbooks, and then became a reporter, writing about health, education, government, Latino affairs, and food. Her lifelong struggle with insomnia and interest in investigative reporting motivated her to write a book, The Savvy Insomniac: A Personal Journey through Science to Better Sleep. She now freelances as an editor and copy writer at On the Mark Editing.


  1. Thanks for reporting on this important issue Lois. It is very true that anything OTC is often considered more “safe” than Rx. People need to be aware that any pharm agent comes with risk!



    1. Yes. And in this case, the concern seems to be mostly for people taking high doses of these anticholinergics on a long-term basis.



  2. I have been taking Xanax (generic) for several years. Is this included in the study. I take 1 mg but I have been breaking them in half lately.



    1. Hi Judie,

      Xanax, whether brand name or generic, is a prescription drug used for anxiety and panic attacks and sometimes prescribed for insomnia. It’s from a family of drugs called benzodiazepines.

      It is not known to have strong anticholinergic effects. So it was not included in the University of Washington study.

      If you click on “University of Washington,” you’ll land on the study abstract. If you click on the link to the full article, you can see the full study. Somewhere in there is a table (again, you have to click another link) of anticholinergic drugs that were included in this study. Xanax, or alprazolam, was not one of them.



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