Is It Safe to Take Benadryl, ZzzQuil or Unisom for Sleep Every Night?

The federal rule for over-the-counter nighttime sleep aids allows them to be sold for occasional sleeplessness and difficulty falling asleep, at 50 mg of diphenhydramine hydrochloride at bedtime for adults and children 12 and over¹. Products sold under that rule must carry this warning: if sleeplessness persists continuously for more than 2 weeks, consult your doctor, because insomnia may be a symptom of a serious underlying medical illness¹. The ZzzQuil label says the same, and so does the label of Unisom SleepTabs, which use doxylamine instead^2,3.

In other words, nightly use for months is outside what the label covers. That does not mean one night is dangerous; it means the product was never meant to treat chronic insomnia.

The American Geriatrics Society's 2023 Beers Criteria list first-generation antihistamines, including oral diphenhydramine and doxylamine, as drugs older adults should avoid (moderate-quality evidence, strong recommendation)⁸. The reasons given: they are highly anticholinergic, the body clears them more slowly with age, tolerance develops when they are used for sleep, and they can cause confusion, dry mouth and constipation. Cumulative anticholinergic exposure is linked to falls, delirium and dementia, even in younger adults⁸.

The best-known study followed 3,434 adults aged 65 and older without dementia for an average of 7.3 years⁹. People with the highest cumulative use of strongly anticholinergic drugs (more than 1,095 standardized daily doses, the equivalent of over 3 years of daily use at the minimum effective dose) had a 54% higher risk of dementia than non-users (hazard ratio 1.54)⁹. First-generation antihistamines were among the most common drugs in that group⁹. It was observational, so it cannot prove the drugs caused dementia. One author had a Merck/American Geriatrics Society award, and two statisticians were paid from Pfizer and Amgen research grants to their institute⁹.