Quick Answer: Melatonin is a hormone that signals night to the body clock. Supplements are not FDA-approved drugs; NCCIH says they may help with jet lag, delayed sleep-wake phase disorder and some childhood sleep problems. Diphenhydramine (in Benadryl and OTC sleep aids such as Unisom SleepGels, 50 mg) is an FDA-regulated OTC drug labeled for occasional sleeplessness; it causes drowsiness by blocking histamine. The AASM 2017 guideline suggests not using either for chronic insomnia. Diphenhydramine causes anticholinergic effects and next-day grogginess and is on the Beers list of drugs older adults should avoid. Melatonin product contents vary widely, and pediatric melatonin poisonings rose 530% from 2012 to 2021.
Melatonin vs Benadryl at a Glance
| Feature | Melatonin | Diphenhydramine (Benadryl, sleep aids) |
|---|---|---|
| Regulatory status | Dietary supplement (not FDA-approved for any use) | OTC drug with FDA Drug Facts label |
| How it works | Signals the body clock that it is night | Blocks histamine H1 receptors in the brain, causing sedation |
| Best-supported use | Jet lag; delayed sleep-wake phase disorder (NCCIH) | Occasional sleeplessness (label) |
| AASM 2017, chronic insomnia | Suggest not using | Suggest not using |
| Next-day grogginess | Possible, usually mild | Common |
| Anticholinergic effects | No | Yes: dry mouth, constipation, urinary retention, confusion |
| Older adults | Use cautiously; ask a clinician | Beers Criteria: avoid |
| Children | Ask a pediatrician; keep out of reach | Sleep-aid labels: not under 12 |
Doses above are from the current U.S. Drug Facts or prescribing labels listed in Sources. Always follow the label on the package you buy, because store brands and formulations differ.
How They Work
Melatonin is produced by the pineal gland as darkness falls and helps set the timing of the sleep-wake cycle. Supplemental melatonin acts more like a timing signal than a sedative, which is why it is studied mainly for circadian problems such as jet lag and delayed sleep phase rather than as a knockout pill.
Diphenhydramine is a first-generation antihistamine. Blocking histamine in the brain causes drowsiness, and the same molecule is the active ingredient in Benadryl Allergy products and in nighttime sleep aids such as Unisom SleepGels and many “PM” pain relievers. It also blocks acetylcholine, causing anticholinergic side effects.
Supplement vs Drug: Why It Matters
Diphenhydramine sleep aids are regulated as OTC drugs, with standardized Drug Facts labels that set the dose, warnings and uses. The Unisom SleepGels label, for example, lists diphenhydramine HCl 50 mg per softgel for relief of occasional sleeplessness.
Melatonin in the US is sold as a dietary supplement, which is not reviewed by the FDA for safety or effectiveness before sale. Content can vary: Erland and Saxena (Journal of Clinical Sleep Medicine, 2017) tested 31 melatonin supplements and found melatonin content ranged from 83% less to 478% more than labeled, with lot-to-lot variation as high as 465%; 8 products also contained serotonin. Choosing a product verified by an independent program such as USP can reduce this uncertainty.
What the Evidence Shows
Melatonin
The National Center for Complementary and Integrative Health (NCCIH) summarizes that melatonin may help with jet lag, delayed sleep-wake phase disorder, some sleep disorders in children, and anxiety before and after surgery. In one review it cites, melatonin reduced the time to fall asleep by about 22 minutes on average in people with delayed sleep-wake phase disorder. For ordinary insomnia in adults, benefits appear small.
Diphenhydramine
Diphenhydramine is labeled for occasional sleeplessness, but evidence for meaningful improvement in sleep is limited, and tolerance to its sedating effect can develop within days of regular use.
The sleep-medicine guideline
The American Academy of Sleep Medicine’s 2017 guideline on pharmacologic treatment of chronic insomnia in adults (Sateia et al.) suggests that clinicians not use diphenhydramine and not use melatonin for sleep onset or sleep maintenance insomnia, both as weak recommendations based on limited benefit. For chronic insomnia, cognitive behavioral therapy for insomnia (CBT-I) is first line.
Dosing
Diphenhydramine sleep aids: per the Unisom SleepGels label, adults and children 12 and over take one 50 mg softgel at bedtime if needed, or as directed by a doctor. Do not use with any other product containing diphenhydramine, including ones used on the skin.
Melatonin: supplements commonly range from under 1 mg to 10 mg or more. Because there is no FDA-set dose, many clinicians suggest starting with a low dose and timing it a few hours before the desired bedtime when the goal is shifting the body clock. See our melatonin dose comparison for more.
Safety
Diphenhydramine
- Next-day effects: drowsiness, slowed reaction time and impaired driving the next morning.
- Anticholinergic effects: dry mouth, constipation, blurred vision, urinary retention and confusion. The label says to ask a doctor before use with glaucoma, trouble urinating due to an enlarged prostate, or breathing problems such as emphysema or chronic bronchitis.
- Older adults: the American Geriatrics Society Beers Criteria list diphenhydramine as a drug older adults should avoid because of confusion, falls and other anticholinergic harms.
- Overdose: the FDA has warned that taking more than the recommended dose can cause serious heart problems, seizures, coma or death.
- Duration: the label says to stop and ask a doctor if sleeplessness persists continuously for more than 2 weeks, since insomnia may be a symptom of a serious underlying illness.
Melatonin
- Short-term side effects are usually mild: headache, dizziness, nausea and sleepiness.
- Children: Lelak and colleagues (CDC MMWR, 2022) reported 260,435 pediatric melatonin ingestions to U.S. poison centers from 2012 to 2021, with the annual number increasing 530%, and rising hospitalizations, mostly from unintentional ingestions by children 5 and under. Store gummies out of reach.
- Long-term use: NCCIH notes that long-term safety has not been well studied.
- Interactions: ask a clinician if you take blood thinners, seizure medicines, diabetes medicines or immunosuppressants.
Can You Take Them Together?
Combining a sedating antihistamine with melatonin may increase drowsiness and next-day impairment, and there is little evidence that combining them improves sleep. Ask a pharmacist before combining sleep products, and never combine either with alcohol.
Matching the Product to the Problem
- Jet lag or a shifted body clock: melatonin is the better-studied option, per NCCIH.
- An occasional bad night: diphenhydramine is labeled for this, but expect grogginess, and older adults should avoid it.
- Insomnia most nights for 3 months or more: see a clinician about CBT-I rather than relying on either.
- Children: talk with a pediatrician first; diphenhydramine sleep aids are not for children under 12.
Diphenhydramine vs Doxylamine Sleep Aids
Not every OTC sleep aid contains diphenhydramine. Doxylamine succinate is another sedating antihistamine used in products such as Unisom SleepTabs and ZzzQuil Ultra. The ZzzQuil Ultra label lists doxylamine succinate 25 mg per tablet to help reduce difficulty in falling asleep, with directions for adults and children 12 and over to take one tablet 30 minutes before bed, once daily. Its warnings mirror diphenhydramine’s: do not use in children under 12; ask a doctor first with asthma, emphysema, chronic bronchitis, glaucoma or trouble urinating due to an enlarged prostate; avoid alcohol; and stop and ask a doctor if sleeplessness persists for more than 2 weeks.
Watch for Hidden Diphenhydramine
Diphenhydramine appears in many combination products, including nighttime pain relievers (labeled “PM”), nighttime cold medicines and topical anti-itch creams. The Unisom SleepGels label warns not to use it with any other product containing diphenhydramine, even one used on the skin. Check the active ingredients on every product you take at night to avoid accidental double dosing.
When to Talk to Your Doctor or Pharmacist
See a clinician if sleeplessness lasts more than 2 weeks, if you snore loudly or stop breathing during sleep, if you feel sleepy while driving, or before giving any sleep product to a child. Call Poison Control (1-800-222-1222) or 911 if a child swallows melatonin gummies or if anyone takes too much diphenhydramine, especially with confusion, a racing heartbeat or seizures.
Frequently Asked Questions
Is melatonin or Benadryl better for sleep?
They serve different purposes. Melatonin is better studied for jet lag and body-clock problems; diphenhydramine is labeled for occasional sleeplessness. The AASM suggests not using either for chronic insomnia.
Can I take melatonin and Benadryl together?
Ask a pharmacist first. Combining them may increase drowsiness and next-day impairment without clear added benefit.
Is Benadryl safe to take every night for sleep?
Not recommended. Tolerance develops, anticholinergic side effects add up, and the label says to see a doctor if sleeplessness lasts more than 2 weeks. Older adults should avoid it.
Is melatonin FDA approved?
No. In the US, melatonin is sold as a dietary supplement, which is not FDA-approved, and product contents can vary from the label.
Does melatonin cause grogginess?
It can, though it is usually milder than with diphenhydramine. Higher doses or late timing may increase morning sleepiness.
Is Unisom the same as Benadryl?
Unisom SleepGels contain diphenhydramine, the same ingredient as Benadryl. Unisom SleepTabs contain a different antihistamine, doxylamine.
Sources
- DailyMed: Unisom SleepGels (diphenhydramine HCl 50 mg) Drug Facts
- NCCIH: Melatonin: What you need to know
- PubMed: Sateia et al., AASM clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults (2017)
- PubMed: Erland and Saxena, melatonin natural health products and supplements: serotonin and significant variability of melatonin content (2017)
- PubMed: Lelak et al., pediatric melatonin ingestions, United States, 2012–2021 (MMWR, 2022)
- PubMed: American Geriatrics Society 2023 updated AGS Beers Criteria
- FDA: FDA warns about serious problems with high doses of the allergy medicine diphenhydramine (Benadryl)
- MedlinePlus: Diphenhydramine
- DailyMed: ZzzQuil Ultra (doxylamine succinate 25 mg) Drug Facts
Medical disclaimer: This article is for educational purposes and does not replace medical advice. Consult a licensed healthcare provider before starting any supplement, medication, or treatment — particularly if you are pregnant, breastfeeding, taking other medications, or have a diagnosed medical condition.