Comparing Over-the-Counter Sleep Medications

Different sleep aids have different benefits and risks

Table of Contents
View All
Table of Contents

If it's 3:00 a.m. and your mind is ticking away⁠—making grocery lists, balancing your budget, or preparing tomorrow's to-do list—your insomnia is likely nothing to worry about. However, if this continues for several nights, it may be reasonable to reach for an over-the-counter (OTC) sleep remedy.

Persistent insomnia poses serious health concerns if left untreated, including an increased risk of high blood pressure, type 2 diabetes, and congestive heart failure. Even occasional insomnia can decrease productivity while increasing the risk of accidents and depression.

A young woman sitting on her bed at home and taking pills with water - stock photo

Emir Memedovski / Getty Images

This article looks at four OTC sleep remedies that may help treat occasional insomnia. Two are antihistamines that can make you feel drowsy. The other two are natural remedies believed to aid with sleep.


Diphenhydramine is an antihistamine typically used to treat allergies. It is also the active ingredient in the OTC cold and flu remedy Benadryl.

Diphenhydramine has sedative properties, meaning that it can make you drowsy and help you sleep. The effect can last for up to seven hours.

There are several versions of diphenhydramine available (including diphenhydramine citrate, diphenhydramine hydrochloride, and diphenhydramine tannate), none of which are inherently better than the other.

Simply Sleep, Nytol, Sominex, and 40 Winks are just some of the OTC sleep aids in which diphenhydramine is the active ingredient. Generic versions are also available.


The recommended dose of diphenhydramine for adults and children 12 and over is 50 milligrams (mg) at bedtime. Diphenhydramine citrate may require a dose of up to 76mg.

Diphenhydramine should only be used in younger children under the direction of a pediatrician. It should never be given to children 2 or younger.

When taken as directed, diphenhydramine is unlikely to be addictive. If you find you need to take a diphenhydramine sleep aid more than three times weekly, talk to your healthcare provider about finding a more appropriate and effective treatment.

Side Effects and Risks

In addition to sleepiness, side effects of diphenhydramine include nausea, headache, and dry mouth. Most side effects are mild and will resolve within 24 hours. If they persist or are severe, stop taking the drug and let your healthcare provider know. You should also call your healthcare provider if you have trouble urinating.

If you are on medications for anxiety or depression, get your healthcare provider's approval before taking diphenhydramine. You should never take diphenhydramine with a type of antidepressant called a monoamine oxidase inhibitor (MAOI). Doing so can cause seizures, hallucinations, and a severe drop in blood pressure.

Diphenhydramine should never be used with alcohol. If you experience daytime drowsiness after taking diphenhydramine, do not drive or use heavy machinery until you feel fully alert again.


Diphenhydramine is an antihistamine commonly used to treat allergies that have sedative effects. It is also found in over-the-counter sleep aids like Sominex and Nytol as well as the popular cold & flu remedy Benedryl.

Doxylamine Succinate

Doxylamine succinate is another antihistamine with sedative effects. Popular sleep aids containing doxylamine succinate include Unisom SleepTabs, Wal-Som, and Nighttime Sleep Aid. It is also available in generic form.


The recommended dose of doxylamine succinate for adults and children over 12 is 25mg taken 30 minutes before bedtime. It should never be given to children under 12.

Side Effects and Risks

In addition to sleepiness, side effects of doxylamine succinate include nausea, chest congestion, nervousness, excitability, and a dry mouth, nose, or throat. Let your healthcare provider know if these side effects are severe or persist.

Call your healthcare provider immediately if you experience changes in vision or have trouble urinating.

Doxylamine succinate should never be taken with alcohol or other medications that cause sleepiness (such as cold and flu remedies). Doxylamine succinate should never be taken with an MAOI antidepressant.

Doxylamine succinate is as effective as diphenhydramine but tends to work longer. For this reason, you should not take it the night before a busy morning schedule. You should also take care not to drive or use heavy machinery until your head is fully clear.

Contact your healthcare provider if you need to take doxylamine more than three times weekly or if insomnia persists.


Doxylamine succinate is an antihistamine with sedative effects that tends to work longer than diphenhydramine. It can be found in OTC sleep aids such as Unisom. Unlike diphenhydramine, doxylamine succinate should not be used in children under 12.


Melatonin is a naturally occurring hormone that helps regulate the sleep-wake cycle. This is the 24-hour pattern consisting of roughly 16 hours of daytime wakefulness and eight hours of nighttime sleep. The regular release of melatonin from the pineal gland stimulates drowsiness and sleep.

There are two types of melatonin sold as an OTC remedy: one is manmade and the other is derived from the pineal gland of animals.

The effectiveness of melatonin varies based on who you speak to. Some people claim that it works and leaves them feeling refreshed the next morning. Others experience no benefits.

According to a 2013 review of studies published in PLoS One, the effectiveness of melatonin for occasional insomnia is modest. There is some evidence that it can help people fall asleep faster and stay asleep for slightly longer.

On the downside, the effect seems to decrease the longer you take melatonin. As such, it should only be used for the short-term relief of insomnia when needed.


There is no recommended dose of melatonin. Generally speaking, higher doses deliver better results. Most manufacturers recommend between 0.5mg and 3mg taken 30 minutes before bedtime.

Due to the lack of safety research, melatonin should not be given to children, pregnant women, or nursing mothers.

Side Effects

Melatonin is likely the safest OTC sleep aid. Excess melatonin is quickly cleared from the body and does not accumulate. Side effects are rare but may include headache, nausea, and vivid dreams.


Melatonin is a hormone that stimulates sleep as part of the sleep-wake cycle. It is the safest OTC sleep aid with few, if any, side effects. Even so, some people feel no effect after taking melatonin while others do.

Valerian Root

Valerian root (Valeriana officinalis) has been used for centuries to treat insomnia. It contains a substance called valerenic acid that is believed to activate cells in the brain called gamma-aminobutyric acid (GABA) receptors. GABA is responsible for slowing nerve signals. By activating these cells, valerian root may deliver a calming, sedative effect.

Despite its long-standing use in traditional cultures, the effectiveness of valerian root in treating insomnia is uncertain. According to a 2015 report in Sleep Medicine Reviews, valerian root had no discernible effect on insomnia.


There is no recommended dose for valerian root. Most valerian supplements are formulated in doses ranging from 300mg to 600mg and are considered safe within this range.

Due to the lack of safety research, children, pregnant women, and nursing mothers should not take valerian root.

Side Effects and Risks

Side effects of valerian root tend to be mild and may include headache, dizziness, itchiness, upset stomach, dry mouth, vivid dreams, and daytime drowsiness.

Although rare, liver damage can occur if valerian root is used excessively. This is especially true if "wild-crafted" valerian root is used, which may be contaminated with heavy metals, fertilizers, and other toxic substances.

Stop taking valerian root if use if you have signs of liver injury, including abdominal pain, nausea, clay-colored stools, dark urine, extreme fatigue, or jaundice (yellowing of the eyes or skin).


Valerian root is a herbal supplement thought to have calming effects and aid with sleep. To date, there is little evidence that it can help treat insomnia.


If you have occasional insomnia, it may be reasonable to use an over-the-counter (OTC) sleep aid containing the antihistamine diphenhydramine or doxylamine succinate.

Diphenhydramine is found in OTC sleep aids like Sominex and Nytol, while doxylamine succinate is found in OTC sleep aids like Unisom. Doxylamine succinate tends to work longer and, unlike diphenhydramine, cannot be used in children under 12.

The effectiveness of natural sleep remedies like melatonin and valerian root is less certain. Melatonin appears to work in some people but not in others. The evidence supporting the use of valerian root for insomnia is generally weak. If overused, valerian root can cause liver damage.

A Word From Verywell

Insomnia doesn't always require medication. In fact, improved sleep hygiene is often all that is needed to get a good night's rest. This includes not eating before bedtime, turning off electronics at least an hour before sleep, keeping the room temperature cool, and ensuring the bedroom is as dark and quiet as possible.

If insomnia persists despite your best efforts, see your healthcare provider. A prescription sleep aid may be useful in treating occasional insomnia if used correctly and under medical supervision.

8 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Javaheri S, Redline S. Insomnia and risk of cardiovascular diseaseChest. 2017;152(2):435-44. doi:10.1016/j.chest.2017.01.026

  2. Byrne EM. The relationship between insomnia and complex diseases—insights from genetic data. Genome Med. 2019;11:57. doi:10.1186/s13073-019-0668-0

  3. Abraham O, Schleiden L, Albert SM. Over-the-counter medications containing diphenhydramine and doxylamine used by older adults to improve sleepInt J Clin Pharm. 2017;39(4):808-17. doi:10.1007/s11096-017-0467-x

  4. Lie JD, Tu KN, Shen DD, Wong BM. Pharmacological treatment of insomniaP T. 2015;40(11):759-71.

  5. Khan S, Saud S, Khan I, et al. Serotonin syndrome presenting with concomitant tramadol and diphenhydramine use: A case report of an unlikely side-effectCureus. 2018;10(4):e2421. doi:10.7759/cureus.2421

  6. Ferracioli-Oda E, Qawasmi A, Bloch MH. Meta-analysis: melatonin for the treatment of primary sleep disordersPLoS One. 2013;8(5):e63773. doi:10.1371/journal.pone.0063773

  7. Leach MJ, Page AT. Herbal medicine for insomnia: A systematic review and meta-analysis. Sleep Med Rev. 2015;24:1-12. doi:10.1016/j.smrv.2014.12.003

  8. Kia YH, Alexander S, Dowling D, Standish R. A case of steroid-responsive valerian-associated hepatitisIntern Med J. 2016;46(1):118-9. doi:10.1111/imj.12952

By Naveed Saleh, MD, MS
Naveed Saleh, MD, MS, is a medical writer and editor covering new treatments and trending health news.