Over-the-Counter Sleep Aids: Do They Work?

The pharmacy sleep aisle is arranged like a ladder: gentle herbal things at one end, "maximum strength" at the other, all of it available without asking anyone. That arrangement says nothing about whether any of it is a good idea nightly. Products marketed for sleep contain a mix of melatonin, sedating antihistamines and herbal ingredients. They may have a place for short-term use; for long-running insomnia, other options are better supported.

What is actually in the box

Nearly every non-supplement over-the-counter sleep aid in the US contains a first-generation antihistamine, usually diphenhydramine or doxylamine. These are allergy medicines. Drowsiness was the side effect that made them a drawback for hay fever — and the reason they were repurposed for sleep.

They work in the narrow sense that they make you sleepy. Whether that amounts to treatment is the question the guidelines answer.

Do they work?

For a short time, and for mild insomnia, there is some evidence. In a trial of 184 adults with mild insomnia, 50 mg of diphenhydramine nightly for two weeks modestly improved sleep efficiency and self-rated insomnia severity compared with placebo.4

In a trial of adults aged 70 to 89, the same dose for fourteen nights reduced the number of awakenings — 1.7 against 2.0 on placebo — without improving other sleep measures.5

The bigger problem is that the effect fades. Tolerance to the sedative effect of diphenhydramine has been shown to develop within about three days of continuous use.6 That matches what most nightly users describe: it worked for a few nights, then it stopped.

This is why these labels say they are for occasional sleeplessness, and tell you to stop and seek medical advice if sleeplessness persists beyond two weeks — wording set by the FDA monograph that governs the category.7

The age problem

For older adults there is a further issue. The American Geriatrics Society's Beers Criteria identify medications that are potentially inappropriate in adults 65 and over, and advise avoiding first-generation antihistamines. The stated rationale:

"Highly anticholinergic; clearance reduced with advanced age, and tolerance develops when used as hypnotic; risk of confusion, dry mouth, constipation, and other anticholinergic effects or toxicity."2

That is a strong recommendation on moderate-quality evidence — stronger than anything in the AASM's medication guideline, where every recommendation is graded weak.

Two parts of that reasoning apply well beyond 65. Tolerance develops when the drug is used as a hypnotic. And the anticholinergic effects — dry mouth, constipation, next-day fog — are not confined to older people; they are simply harder to tolerate as you age.

What the sleep guidelines say

The AASM's 2017 guideline on drug treatment for chronic insomnia reviewed diphenhydramine among fourteen agents, and suggests clinicians not use it for sleep-onset or sleep-maintenance insomnia.1 The same guideline reaches the same verdict on the supplements sold beside it: melatonin, valerian and L-tryptophan all carry recommendations against use for insomnia.1

The 2025 VA/DoD guideline also suggests against diphenhydramine for chronic insomnia.3

What the guidelines put first

Chronic insomnia means trouble sleeping three or more nights a week for at least three months, with a consequence during the day. For that, the American College of Physicians recommends CBT-I as the first treatment for all adults — a strong recommendation on moderate-quality evidence.8 It is also the only treatment with a strong recommendation in the AASM's 2021 behavioral guideline.9

CBT-I is short-term, and it works on the thoughts and habits that keep insomnia going: a consistent schedule, less time awake in bed, and ways to handle a racing mind.

Not a supplement. Not an antihistamine. And not something you have to stop anything else in order to start.