Sleep Disorders Treatment Unisom vs Benadryl: Which Sleep Aid Is Best for You? Benefits and Risks of Doxylamine (Unisom) and Diphenhydramine (Benadryl) By Naveed Saleh, MD, MS Updated on November 21, 2023 Medically reviewed by Isaac O. Opole, MD, PhD Print Table of Contents View All Table of Contents How Sleep Aids Work Side Effects How to Take Contraindications Alternatives Benadryl (diphenhydramine) and Unisom (doxylamine succinate) are sleep aids that can be purchased over the counter. Both medications are antihistamines that have sedative side effects. Generic versions are also available. These medications are meant to treat short-term sleep problems. If you experience occasional insomnia, you can use either Benadryl or Unisom to help you get to sleep faster. You can also try alternative OTC sleep aids like melatonin or valerian. This article discusses the OTC sleep remedies Benadryl and Unisom and their benefits, side effects, and contraindications. Emir Memedovski / Getty Images Causes of Chronic Insomnia How Do Benadryl and Unisom Help With Sleep? The active ingredient of Benadryl is diphenhydramine, an antihistamine medication with sedative properties, meaning that it can help you sleep. Diphenhydramine works by blocking natural substances called histamines. This also has the effect of making you feel drowsy. The sedative effect of diphenhydramine 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 others. Some of the sleep aids that have diphenhydramine as an active ingredient include: Simply SleepNytolSominex40 Winks Generic versions are also available. Unisom's active ingredient is the antihistamine doxylamine succinate. Doxylamine succinate is as effective as diphenhydramine but tends to work longer, for up to eight hours. Popular sleep aids containing doxylamine succinate include: Unisom SleepTabs Wal-Som Nighttime Sleep Aid It is also available in generic form. Other Uses For Unisom and Benadryl The active ingredients in Unisom and Benadryl are antihistamines. These medications are also used to treat seasonal allergies. Diphenhydramine is also the active ingredient in the OTC cold and flu remedy Benadryl. Side Effects Besides drowsiness, Benadryl and Unisom can both have unwanted side effects. Benedryl Side Effects Side effects of diphenhydramine include: NauseaHeadacheDry 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. Unisom Side Effects Side effects of doxylamine succinate include: NauseaChest congestionNervousnessExcitabilityDry 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. 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. How to Take Unisom and Benedryl The recommended dose of doxylamine succinate for adults and children over 12 is 25 mg taken 30 minutes before bedtime. It should never be given to children under 12. 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 76 mg. 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, OTC sleep aids are unlikely to be addictive. If you find you need to take diphenhydramine or doxylamine succinate more than three times weekly, talk to your healthcare provider about finding a more appropriate and effective treatment. Contraindications for Unisom and Benadryl If you are on medications for anxiety or depression, get your healthcare provider's approval before taking Unisom or Benadryl. You should never take either of these medications 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 and doxylamine succinate should never be taken with alcohol or other medications that cause sleepiness (such as cold and flu remedies). If you experience daytime drowsiness after taking these medications, do not drive or use heavy machinery until you feel fully alert again. Do not take the night before a busy morning schedule. Alternatives to Unisom and Benadryl for Help Sleeping If you find the side effects of Unisom or Benadryl intolerable, you may want to try another OTC sleep remedy. Melatonin 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. Some people claim that it works and leaves them feeling refreshed the next morning. Others experience no benefits. A 2019 review of studies found that melatonin can help improve sleep quality in people with secondary sleep disorders. The study authors also noted, however, that more research needs to be done in order to establish the long-term safety of melatonin. 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. Melatonin for Kids: Dos and Don’ts for Parents Dosage 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. 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. Dosage There is no recommended dose for valerian root. Most valerian supplements are formulated in doses ranging from 300 mg to 600 mg 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). Can I Take Antihistamines During Pregnancy? Summary 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. 9 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. Abraham O, Schleiden L, Albert SM. Over-the-counter medications containing diphenhydramine and doxylamine used by older adults to improve sleep. Int J Clin Pharm. 2017;39(4):808-17. doi:10.1007/s11096-017-0467-x Lie JD, Tu KN, Shen DD, Wong BM. Pharmacological treatment of insomnia. P T. 2015;40(11):759-71. Javaheri S, Redline S. 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